Abstracts - Table of Contents

会议发言 Lecture. 10

A Glio-Centric View of Repair. 10

Developing history and some new conceptions in Neurorestoratology. 11

The international associations and societies related to cell therapy research and treatment 12

Long-term Follow-up Observation on 24 Patients with Spinal Cord Injury Receiving Olfactory Ensheathing Cell Transplantation. 13

脊髓损伤嗅鞘细胞移植24例中期随访观察... 13

Pharmacotherapy: Progress in Neurorestoratology. 14

Monitoring and Neuromodulation of motor control after spinal cord injury. 15

Functional Significance of Adult Neurogenesis in the Mammalian Brain. 16

A neonatal mouse SCI model for testing human stem cells including high throughput functional imaging of synaptic connections 16

Stereotaxic implantation of Olfactory ensheathing cells OECsfor stroke patients 17

Muse cells, a novel type of adult human pluripotent stem cells that reside in mesenchymal tissues: their great possibility for regenerative medicine. 18

Pathways to Protection from Pediatric Anesthetics 19

Clinical efficacy of the neural precursor cells transplantation to treat the severe visual impairment – a sequela of neonatal brain injury. 20

Integrated Regenerative Therapy Program (IRTP) for management of Autism and other disorders 21

Clinical results of autologous bone marrow derived adult stem cell transplantation in muscular dystrophy  23

Repair of Spinal Injury: Caution and Hope. 24

Central Nervous System Injury and Repair. Role of Nanomedicine, Stem Cells, Antibodies and other Therapeutic agents 27

Post-Genome Technologies in Neurorestoratology: from Mapping and Profiling of Stem Cell Proteome to the Development of Personalized Cell Preparations for Regenerative Therapy of Neural Disorders 28

The crosstalk between vascular and degenerative mechanism in neurocognitive disorders. Is there a place for endogenous neurogenesis?. 31

Cognitive Neural Rehabilitation. 32

Nanomedicine and Central Nervous System: the application, the perspectives and the future. 33

Four Essential Aspects to Procure the Complente Recovery of cSCI Patients 34

Development of an International Accreditation System for Stem Cell-Based Therapies 35

Coding and traceability of Cell and Tissue products in Iran. 37

The Long-term outcomes for patients with sequela of stroke through multiple kinds of cell transplantation  38

多种细胞移植治疗脑卒中后遗症远期随访结果... 39

Intracerebral implantation of Stem Cells Promotes the Regeneration of Corticospinal Tracts in Stroke Patients 39

Neuroprotective and Neuroregenerative Trophic Molecules in Parkinson ’s disease. 40

The use of distraction osteogenesis technique in stroke management 42

Long –term follow up results for patients with chronic spinal cord injury by autologous mesenchymal stem cell transplantation. 42

Clinical Observation of Fetal Olfactory Ensheathing Glia Transplantation(OEGT)in Patients With Complete Chronic Spinal Cord Injury. 43

Side-To-Side Neurorrhaphy for High-Level Peripheral Nerve Injuries 44

Requirements for Interventions to prove Added Value to Neurological Recovery following Traumatic Spinal Cord Injuries 45

Morbidity Aspects in Spinal Cord Injury with Insights into the Transplantation of Stem Cells in the Injured Cord  47

Rehabilitation of Chronic Spinal Cord Injured Patients after Cellular Therapy. 48

Research and Analysis about Myelotomy in the Treatment of Spinal Cord Injury. 49

Mobilization of bone marrow progenitor cells as novel marker of regenerative potential in traumatic brain injury  49

Promoting Peripheral Axon Regeneration and Neurological Recovery with Blood-born Cells 51

Olfactory Mucosa Transplantation for Spinal Cord injury. 52

Safety of granulocyte-colony stimulating factor (G-CSF) administration in spinal cord injury patients 53

Transplantation of Autologous Activated Schwann Cells in the Treatment of Spinal Cord Injury, Six cases, more than Five years’ follow-up. 54

Comparative Analysis of Long-Term Outcomes of Various Stem Cell Therapies of Spinal Cord Injury in Humans 55

Transplantation of Umbilical Cord Blood Mononuclear Cells for the Treatment of Patients with Delayed Encephalopathy after Carbon Monoxide Intoxication. 57

脐血单个核细胞移植治疗一氧化碳中毒后迟发性脑病... 57

Change of Spasticity following Robotic-Assisted Gait Training in Patients with Chronic Incomplete Spinal Cord Injury: Preliminary Results 58

Hip and Knee Joint Trajectories in Sagittal Plan following Robotic-Assisted Gait Training in Patients with  Incomplete Spinal Cord Injury: Preliminary Results 59

福音截瘫患者康复训练机器人报告... 60

Safety of Intramedullary Autologous Peripheral Nerve grafts For Post-rehabilitated Spinal Cord Injuries 61

Psychosocial problems of spinal cord injury patients 62

Cardio metabolic risk factors in spinal cord injured people: An analysis by injury related variables 63

HMGB-1/RAGEHMGB-1/TLRs信号通路诱导脊髓损伤后继发性炎症反应的实验研究... 64

Bromocriptine prevents spinal motor neurons in vitro and in vivo. 65

Protein kinases as therapeutic targets for central nervous system disorders 67

Augurin: A choroid plexus-CSF secreted peptide derived from the Ecrg4 gene with a putative role in regulating periventricular neurogenesis following traumatic brain injury. 68

Effects of Intra-Peritoneal Injection of Crocin on Contused Rat Spinal Cord. 69

Calcium and vitamin D in spinal cord injury. 70

神经调控改善癫痫发作及预后... 70

Deep Brain Stimulation and the induction of Neurogenesis. Possible therapeutic strategies for Parkinson’s disease, Depression and Stroke. 71

Promoting Neural Stem Cells Differentiation and Alignment under Electric Stimulation. 73

Nanotechniques: Neurorestoration at the Cellular Level 74

The effects of electrospun TSF nanofiber diameter and alignment on growth, migration and neural differentiation of mesenchymal stem cells 74

Regulated delivery of GDNF gene using bone marrow-derived stem cells transduced with a lentiviral vector into mouse brain. 75

Olfactory Ensheathing Cells on Electrospun Nanofibres 76

Olfactory Ensheathing Cells on Electrospun Nanofibres 77

Evaluation Effect of Acupuncture and Neural stem cells and their combination therapy on Newborn Rats with Cerebral palsy. 78

针刺和神经干细胞联合治疗脑瘫幼鼠的效果评价... 78

Neural stem cells counteract traumatic brain injury via modulating an unexpected smooth muscle protein in neurons 79

Neural Potential of Human Cord Blood and Umbilical Cord Cells:a Successful Translation. 80

Wharton jelly - natural scaffold and the rich source of mesenchymal stem cells 81

Different Neuroprotection and Therapeutic Time Windows by Two Specific Diazepam Regimens on Retinal Ganglion Cells after Optic Nerve Transection in Adult Rats 82

Enhanced neuronal differentiation potential in dedifferentiated human bone marrow-derived MSCs 83

Human spinal cord-derived neural stem cells (HSSC) for treatment of neurological diseases 83

Gene-modified Mesenchymal Stem Cells for Neural Regeneration: Translating Clinical Experience in Chronic Stroke to Spinal Cord Injury. 84

Clinical trial to investigate the use of Cethrin to restore functionafter spinal cord injury. 85

Umbilical Cord Blood Mononuclear Cell Therapy of SCI and Stroke. 85

嗅鞘细胞移植治疗陈旧性脊髓损伤疗效长期随访观察... 86

自体骨髓干细胞治疗脊髓损伤32... 87

晚期脊髓损伤患者嗅鞘细胞移植术后交感神经皮肤反应变化的临床研究... 87

Intravenous transplantation of human umbilical cord-derived mesenchymal stem cells for the treatment of acute spinal cord injury in rats 88

静脉移植人脐带间充质干细胞治疗急性脊髓损伤的实验研究... 89

白藜芦醇对大鼠急性脊髓损伤的神经保护效应... 89

Treatment of rat’s spinal cord injury with Autologous Activated Schwann Cells via different grafting routes 90

不同途径移植自体激活雪旺细胞修复大鼠脊髓损伤... 91

Control of olfactory ensheathing cell behaviors by electrospun. 91

silk fibroin nanofibers 92

人雪旺细胞促进人脐带间充质干细胞向神经方向分化的研究... 92

The research of neural differentiation of hUC-MSCs promoted by hSCs 93

自体骨髓间充质干细胞回输治疗脑卒中30例报告... 94

干细胞联合移植对脑卒中临床作用的初步研究... 94

脐带间充质干细胞治疗运动神经元病的一年期临床研究... 95

clinical reports of multiple cells therapy for treating multiple system atrophy. 96

多种细胞移植治疗多系统萎缩患者临床报告... 97

氯化锂调节tau蛋白磷酸化及改善脑缺血大鼠学习与记忆能力的机制研究... 98

细胞移植在疼痛神经修复学中的应用进展... 98

神经生物支架在神经修复中的研究进展... 99

Exercise Enhances Learning and memory and Hippocampal Neurogenesis 99

运动训练增强小鼠空间学习记忆能力及海马神经发生的观察... 100

重组腺相关病毒rAAV- Nogo66-siRNA-IRES-hNGF-β介导基因表达的时效性... 101

川芎嗪对大鼠脊髓损伤后血管再生的作用及其与HIF-1aVEGF表达的关系... 102

纯中药制剂对感音神经性聋耳蜗毛细胞修复再生的实验研究... 103

A Study on Effect of SDF-1α/CXCR4 Axis in vitro Migration of Human Umbilical Cord Mesenchymal Stem Cells 104

SDF-1α/CXCR4轴在人脐带间充质干细胞体外迁移的实验研究... 104

21例脊髓损伤病例的病理分析... 105

Intracerebral transplantation of adipose-derived mesenchymal stem cells ameliorate neuropathological deficits in Alzheimer`s disease mice by activation of microglia. 105

脂肪干细胞脑内移植激活小胶质细胞改善阿尔茨海默症神经功能... 106

Efficient generation of neural precursors from rat adipose-derived stem cells 106

大鼠脂肪干细胞高效率向神经祖细胞诱导分化的研究... 107

丙戊酸钠对分化中的人海马神经元凋亡的影响及作用机制... 108

The influence of SIRT1 on the inflammation in rat acute spinal cord injury. 108

移植人脐血干细胞提高脊髓损伤损伤中心血管密度与组织活力的实验研究... 109

Clinical results of autologus bone marrow mononuclear cells in 75 chronic spinal cord injury patients 110

齿状突骨折临床治疗生存质量的研究... 110

Myelin is a major survival factor for macrophages and alters influence in microenvironment of injured spinal cord  111

脊髓损伤后髓磷脂刺激巨噬细胞长期存活及改变损伤区微环境的机制研究... 112

The Treatment of Acute Spinal Cord Injury by Combined Transplantation of Activated Schwann Cells and Human Umbilical Cord Blood Mesenchymal Stem Cells 112

激活态雪旺细胞联合脐血间充质干细胞移植修复脊髓损伤的实验研究... 114

The study of changes and relationship between astrocytes and neural stem cells of adult rat subventricual zone after traumatic brain injury. 115

Research of PEG-TAT-modified cyclosporine A-loaded PLGA/polymeric liposomesto Cross the Blood-Spinal Cord Barrier for treating Spinal Cord Injury. 116

Hints on Scientific Presentation at Meetings 116

发言投稿Submission. 119

神经修复学临床细胞治疗技术答疑——斧正概念,厘清疑惑... 119

氯化锂调节tau蛋白磷酸化及改善脑缺血大鼠学习与记忆能力的机制研究... 127

Lithium chloride regulates the phosphorylation of tau protein and improvesspatial learning and memory of rats subjected to brain ischemia and reperfusion. 127

移植人脐血干细胞提高脊髓损伤损伤中心血管密度与组织活力的实验研究... 128

Transplantation of human umbilical cord blood stem cells to repair blood vessels and increase vitality of tissue at the injury site. 129

人雪旺细胞促进人脐带间充质干细胞向神经方向分化的研究... 130

The research of neural differentiation of hUC-MSCs promoted by hSCs 130

脊髓型颈椎病前路手术疗效及相关影响因素分析... 131

Analysis of effect and influencing factors of anterior decompression for cervical spondylotic myelopathy  132

激活态雪旺细胞联合脐血间充质干细胞移植修复脊髓损伤的实验研究... 133

The Treatment of Acute Spinal Cord Injury by Combined Transplantation of Activated Schwann Cells and Human Umbilical Cord Blood Mesenchymal Stem Cells 134

骨髓间充质干细胞促进大鼠脊髓损伤后行为功能的恢复... 135

Graft of Bone Mesenchymal Stem Cells Promotes Rat’s Functional Recovery after Spinal Cord Injury  136

不同途径移植自体激活雪旺细胞修复大鼠脊髓损伤... 137

Treatment of rat’s spinal cord injury with Autologous Activated Schwann Cells via different grafting routes 137

TAT-PEG-多功能脂质体跨脊髓损伤大鼠血脊髓屏障的实验研究... 138

RESEARCH OF NOVEL TAT-PEG LOADED MULTIFUNCTIONAL LIPOSOMES CROSSING BLOOD SPINAL CORD BARRIER AFTER SPINAL CORD INJURY.. 139

SDF-1α/CXCR4轴在人脐带间充质干细胞体外迁移的实验研究... 140

A Study on Effect of SDF-1α/CXCR4 Axis in vitro Migration of Human Umbilical Cord Mesenchymal Stem Cells 140

丙戊酸钠对分化中的人海马神经元凋亡的影响及作用机制... 141

The mechanism of human hippocampal neuronal apoptosis induced. 142

粒细胞集落刺激因子对人神经干细胞移植后新生大鼠体内神经元分化的影响... 143

新生大鼠重度缺氧缺血性脑损伤模型的建立... 144

The establishment of severe hypoxic-ischemic brain damagemodel in neonatal rat 144

高压氧对HIBD新生大鼠人神经干细胞移植后神经细胞凋亡的影响... 145

干细胞移植治疗18例低功能型孤独症初探... 146

间充质干细胞条件培养基对新生大鼠缺氧缺血脑损伤移植神经干细胞凋亡的影响... 146

大鼠脑性瘫痪模型的构建及评估... 147

CD133+细胞移植治疗尿素循环障碍的临床研究... 147

脑源性神经营养因子现况调查研究... 148

突触后密度蛋白在神经损伤修复中的意义... 150

脊髓损伤后NG2NeurocanGFAP表达的变化... 153

前后路联合手术治疗颅颈交界区颈髓压迫症... 154

To treatment cervical cord compress of cranio-cervical junction region with anterior-posterior  approach  surgery  155

现代显微放射影像学技术在中枢神经组织离体微血管成像... 155

研究中的最新应用... 155

川芎嗪对大鼠脊髓损伤后血管再生的作用及其与HIF-1aVEGF表达的关系... 156

CMF联合多孔BCP人工骨在兔腰椎后外侧融合模型中的研究... 157

脐血干细胞联合神经生长因子和康复治疗小儿脑性瘫痪的疗效观察... 158

Effects of Umbilical cord blood stem cell transplantation combined with mouse nerve growth factor and physical rehabilitation on treatment of cerebral palsy children. 158

干细胞治疗家族遗传性萎缩性肌强直1例报告... 160

诱导多能性干细胞治疗脊髓损伤的研究进展... 161

语言康复训练早期介入对中风患者语言功能恢复的影响... 162

改良薄荷冰棒刺激脑卒中后吞咽障碍疗效的观察... 163

间歇导尿与留置导尿在脊髓损伤后膀胱功能康复中的疗效观察... 163

健康宣教对急性脊髓损伤患者心理状态的影响... 164

诱导性多能干细胞的部分生物学特性... 164

经皮椎体成形术治疗胸腰椎压缩性骨折的短期临床观察及治疗体会... 166

脊髓间充质干细胞移植治疗脊髓损伤... 166

可诱导多能干细胞IPS 治疗脊髓损伤的基础研究... 167

Calcium and vitamin D in spinal cord injury. 169

Comparative Analysis of Long-Term Outcomes of Various Stem Cell Therapies of Spinal Cord Injury in Humans 170

Clinical Grade Human Autologous Schwann Cell Manufacturingfor Treatment of Spinal Cord Injury  172

Effects of Intra-Peritoneal Injection of Crocin on Contused Rat Spinal Cord. 172

Promoting Peripheral Axon Regeneration and Neurological Recovery with Blood-born Cells 173

Change of Spasticity following Robotic-Assisted Gait Training in Patients with Chronic Incomplete Spinal Cord Injury: Preliminary Results 175

The use of distraction osteogenesis technique in stroke management 176

Clinical results of autologus bone marrow mononuclear cells in 75 chronic spinal cord injury patients 176

Cardio metabolic risk factors in spinal cord injured people: An analysis by injury related variables 177

Establishing a Clinical Grade Cell Manufacturing Facility in an Academic Center. 178

Human Endometrial Stem Cells as a New Source for Programming to Neural Cells 179

Hip and Knee Joint Trajectories in Sagittal Plan following Robotic-Assisted Gait Training in Patients with  Incomplete Spinal Cord Injury: Preliminary Results 180

Safety of Intramedullary Autologous Peripheral Nerve grafts For Post-rehabilitated Spinal Cord Injuries 181

Coding and traceability of Cell and Tissue products in Iran. 182

Assessment tools  for evaluation of spinal cord injury after neuroregenerative interventions 183

Enhanced neuronal differentiation potential in dedifferentiated human bone marrow-derived MSCs 183

Effects of Spinal cord injury on marital status 184

Psychosocial problems of spinal cord injury patients 185

Local Subcutaneous Cobalamin Injection for Subacute HerpeticNeuralgia: Preliminary results of an observer-blind randomized controlled trial study. 186

人工寰椎齿状突关节置换的动物实验研究... 187

一期后路半椎体切除联合椎间融合治疗脊柱畸形... 188

Adenovira-mediated hypoxia-inducible factor 1-alpha gene therapy for spinal cord injury in rat 189

INRS2012自体骨髓间充质干细胞回输治疗脑卒中30例报告... 189

Clinical Report on Autologous Bone Marrow Mesenchymal Stem Cell Reinfusion for Stroke with 30 Cases 190

骨形态发生蛋白-2及其受体BMPR1b诱导神经干细胞分化的实验研究... 190

21例脊髓损伤病例的病理分析... 191

下颈椎前路减压植骨融合术的三维有限元分析... 191

Three-dimensional Finite Element Analysis on Anterio Decompression and Bone Graft Fusion of Lower Cervical Spine  192

神经修复学临床细胞治疗技术答疑——斧正概念,厘清疑惑... 193

人胚鼻黏膜神经干细胞的分离提纯及培养... 201

Isolation,culture and purification of olfactory ensheathing cells from human fetal olfactory mucosa  202

颈前路减压植骨融合内固定治疗多节段颈椎间盘突出的早期疗效评价... 202

Effect of erigeron breviscapus (Vant.) Hand-Mazz pretreatment on pathology and oxyradical level following spinal cord ischemia-reperfusion injury in rabbits 203

一期环脊髓减压治疗胸腰段脊髓压迫症... 203

大鼠GSK3β及EGFP基因共表达病毒载体构建及转染骨髓间充质干细胞... 204

转化生长因子β1、β3在人骨骼肌纤维化中的作用研究... 205

纯中药制剂对感音神经性聋耳蜗毛细胞修复再生的实验研究... 205

激光技术在脊髓损伤研究的应用... 206

小鼠神经干祖细胞移植对阿尔茨海默病转基因模型小鼠的实验研究... 207

Experimental Study of Mouse Neural stem cells/Progenitors transplantation on Alzheimer's disease Transfer Genetic Mouse Model 207

Morphological properties and proliferation analysis of olfactory ensheathing cells seeding into 3-D collagen-heparan sulfate biological scaffolds 208

嗅鞘细胞在三维胶原蛋白硫酸肝素生物支架中生长的形态特征与增殖特性分析... 209

HMGB-1/RAGEHMGB-1/TLRs信号通路诱导脊髓损伤后继发性炎症反应的实验研究... 210

High-mobility Group Box-1 and Its Receptors Contribute to Proinflammatory Response in the Acute Phase of Spinal Cord Injury. 210

IGF-1对大鼠缺血缺氧神经元p-JNK p-P38表达的影响... 211

Influence of IGF-1 on p-JNK, p-P38 in hypoxia ischemia neurons of rat 212

1椎体爆裂性骨折1... 212

健康教育互动模式在骨科临床护理中的应用... 212

植物再生给人类神经再生的启发、帮助和思考... 213

Evaluation Effect of Acupuncture and Neural stem cells and their combination therapy on Newborn Rats with Cerebral palsy. 214

超短波对糖尿病大鼠创面碱性成纤维细胞生长因子表达的影响... 215

Effect of USW on bFGF expression in the wound of diabetic rats 215

Umbilical cord blood mononuclear cell transplantation for treating spinal cord injury. 216

临床应用型人胚神经干细胞的培养与增值... 216

Culture and proliferation of clinical used human embryonic neural stem cells 217

半乳凝素-1对脊髓损伤大鼠室管膜细胞原位增殖及迁移的影响... 217

Ependymal cells proliferation responses and promoter action of galectin-1 after the adult rat spinal cord injury  218

前、后联合入路一期病灶清除固定治疗多节段胸腰椎结核... 219

骨髓间充质干细胞在临床骨科疾病修复中的应用... 220

Application of bone mesenchymal stem cells in the plerosis of clinical orthopedic diseases 221

Mild Hypothermia Enhanced the Potent Therapeutic Effect of Neural Precursor Cell Transplantation in a Neonatal Mouse Model of Cerebral Hypoxia-ischemia. 221

不同剂量嗅鞘细胞静脉移植治疗急性脊髓损伤的实验研究... 222

Repair of rat spinal cord injury by vein transplantation of different doses of Olfactory Ensheathing cells 223

The influence of SIRT1 on the inflammation in rat acute spinal cord injury. 223

大鼠重型颅脑创伤后急性期肾上腺皮质功能改变及地塞米松的干预作用... 224

Changes in adrenal cortex function and protective effect of dexamethasone following acute severe traumatic brain injury in rats 224

经食道球囊扩张术在卒中后吞咽障碍患者功能恢复后期的作用... 225

组织块法培养人脐带来源间充质干细胞的培养与扩增方法... 226

Apoptosis of lumbar spinal cord neuron in cauda equina syndrome. 226

Efficiency evaluation of short-segmental fixation combined with intermediate screws treatment of thoracolumbar burst fractures: A Meta-analysis of randomized controlled trials 227

运动训练增强小鼠空间学习记忆能力及海马神经发生的观察... 228

Exercise Enhances Learning and memory and Hippocampal Neurogenesis 228

Identification and culture of neural stem cells isolated from adult rat subventricular zone following fluid percussion brain injury. 229

Co-transplantation of OECs and SCs combining treadmill training promote functional recovery from rat with spinal cord contused. 230

一期后路截骨矫形病灶清除植骨内固定治疗多节段脊柱结核并后凸畸形... 231

脊柱手术后并发严重椎管内感染的原因及治疗... 232

原儿茶酸对缺血缺氧脑损伤的保护作用研究... 232

Protective Effects of Protocatechuic Acid on Hypoxic-ischemic Brain Damage. 233

The effects of electrospun TSF nanofiber diameter and alignment on growth, migration and neural differentiation of mesenchymal stem cells 233

儿童无骨折脱位脊髓损伤一例... 234

Efficient generation of neural precursors from rat adipose -derived stem cells 235

大鼠脂肪干细胞高效率向神经祖细胞诱导分化的研究... 235

齿状突骨折临床治疗生存质量的研究... 236

The united transplantation of hMSCs and OECs to cure neuropathic pain and to enhance nerve rehabilitation  236

晚期脊髓损伤患者嗅鞘细胞移植术后交感神经皮肤反应变化的临床研究... 237

静脉移植人脐带间充质干细胞治疗急性脊髓损伤的实验研究... 238

Intravenous transplantation of human umbilical cord-derived mesenchymal stem cells for the treatment of acute spinal cord injury in rats 238

NT-3促进神经干细胞体外增殖作用及相关miRNA筛选... 239

The Effects of SrGAP3 on Rat Neural Stem Cells Survival proliferation and Morphological Maturation  240

Identification and culture of neural stem cells isolated from subventricular zone following injury caused by moderate lateral fluid percussion. 240

成年大鼠液压性脑损伤后室下区神经干细胞的分离培养与鉴定... 241

敲除BMPR1b的神经干细胞移植治疗脊髓损伤... 242

Effects of Edaravone on Neurogenesis in the Penumbra Infarct Zone after Transient Focal Cerebral Ischemia in Rats 243

Edaravone Protects the Newly Generated Cells from Apoptosis in the Subgranular Zone of Dentate Gyrus after Transient Global Cerebral Ischemia in Rats 244

Recanalization of Occluded Large Arteries with Broadened Therapeutic Window for Acute Cerebral Infarction  245

Follow-up Study of Stenting for Ischemic Cerebrovascular Diseases 246

rhEPO对衰老大鼠海马Bcl-2Bax表达的影响... 247

EPO抗衰老作用及其对大鼠海马SIRT1蛋白表达的影响... 248

 

 


会议发言 Lecture

Description: GeoffGeoffrey RaismanUK

Honarary President of IANR for life.

Professor of Neural Regeneration,University College London Director of the Spinal Repair Unit,the Institute of Neurology, Queen Square.

 

A Glio-Centric View of Repair

Ying Li, Daqing Li, Geoffrey Raisman

 The tissue of the CNS consists of an intimate interweaving of two great networks, glial and neuronal which act as a self-regulating corporate entity.  The configuration of astrocytic surfaces is crucial to their participation in the network functions.  Re-configuration of the CNS astrocytic network by incorporation of glial cells from the olfactory system produces a situation permissive for the regeneration of severed CNS nerve fibres.

All damage to the nervous system affects both neurons and glia.  Yet up to now the majority of efforts at repair have largely concentrated on neurons.  After axotomy central neurons do not regenerate their axons.  They fail to upregulate the molecular machinery associated with growth and extension of the cytoskeleton.  But these events are not necessarily due to an intrinsic failure in the neurons. 

That adult neurons retain the ability to grow axons and form new functional connections in the CNS is attested by numerous observations and studies.  It has long been recorded that severed central axons sprout, and can form extensive neuromata.  The introduction of peripheral nerve Schwann cells into the CNS induces long growth of axons from intrinsic central neurons that otherwise fail to regenerate.  After injury to fibre tracts in the CNS, adult axons in both damaged and undamaged tracts sprout new branches which are able to cross great distances through undamaged areas of the CNS and establish functional connections.  Above all, our current view of plasticity is that the neural connections in the adult brain are in a state of continuous change.

None of this supports the view that adult central neurons are intrinsically unable to grow axons or make new synaptic connections.  Equally, it does not support the view that the astrocytic environment of the adult CNS is intrinsically inhibitory to axon growth.  The evidence suggests that the failure of axon regeneration is a local consequence of the reaction of the astrocytes at the injury site and therefore it is to the astrocytic behaviour at this site that repair therapies should be directed.

 

 

Description: 主编照片Hongyun Huang (China)

President,International Association of Neurorestoratology (IANR)

President ,Beijing Hongtianji Neuroscience Academy

Adjunct Professor of Taishan Medical University Member of Editorial Board Cell Transplantation; Chief Editor in Frontiers Neurorestoratology; Associate Editor American Journal of Neuroprotection and neuroregeneration

Developing history and some new conceptions in Neurorestoratology

Hongyun Huang ,Lin Chen, Haitao Xi

Center for Neurorestoratology, Beijing Rehabilitation Center, Beijing

Beijing Hongtianji Neuroscience Academy, Beijing

Neurorestoratology is new independent discipline of neuroscience or medicine; but its development take a long time. Here we summarize its developing history and introduce some new conceptions of Neurorestoratology.

Development history of strategies in Neurorestoratology: tissue and cell transplantation (the earliest tissue transplantation in animal by Thompson in 1890 and the first clinical trial by Backlund and Olson in 1982; the initial OECs transplantation in animal study by Ramón-Cueto, Franklin and Raisamn in 1994,1996,1997,2000 and the earliest clinical trials started by Huang, Lima and Rabinovich in 2001); neurostimulation and neuromodulation  (the first electric field affection by Ingvars in 1920 and clinical deep brain stimulation (DBS) by Bechereva in 1972); medicine and growth factor (nerve growth factor found by Levi-Montalcini and Hamburger in1951 and first clinical use by Olson and Backlund in 1991 and high-dose methylprednisolone therapy in animal study in1982 and clinical trial in 1990 by Young); bioengineering and tissue engineering (Garoni found NI-35and NI-250 in 1998 and clinical trial for polymer-encapsulated cells engineered with CNTF by Bloch in 2004); surgery (cordotomy in animal study by Larson in 1965 and in first clinic for patients by Tachibana in 1984 and neurotisation or nerve bridging in animal study by Hueter in 1871 and simultaneously started in clinic by Zhang and Brunelli in 2000).

Tracing the sense development of Neurorestoratology as a discipline, there are Restorative Neurology (Dimitrijevic in 1985), Restorative Neurosurgery (Liberson in 1987),  Neuroprostheses (Keith in 1988), Neurorestorative Technique or Therapy (Fernández in 1995 and Jiménez-Jiménez in 1997), Restorative Neuroscience (Andres in 2008) and Neurorestoratology (put forward by Huang and Chen in 2008 and defined by IANR in 2009).

Main associations or societies in or related with Neurorestedoratology are below: International Association of Neurorestoratology (IANR), Global College of Neuroprotection and Neuroregeneration (GCNN), American Society for Neural Therapy and Repair (ASNTR), International Society of Restorative Neurology (ISRN), International Neuromodulation Society (INS), The Society For The Study Of Neuroprotection And Neuroplasticity (SSNN), Cell Transplant Society (CTS), International Conference on Neuroprotective Agenda, Network of European CNS Transplantation and Restoration (NECTAR), Asia Pacific Symposium on Neural Regeneration (APSNR) and so on.

Main journals in the field of Neurorestoratology include Cell Transplantation, Restorative Neurology and Neuroscience, Neuromodulation, Frontiers in Neurorestoratology, Ameican Journal of Neuroprotection and Neuroregeneration, Stem cells, Clinical transplantation and so on.

Most important new conceptions in Neurorestoratology list below: second generation of neurorestorative therapy (2G- neurorestorative therapy), active movement-target enhancement-rehabilitation therapy (AMTENT), key point for neural network restoration (KPNNR), pain Neurorestoratology, epilepsy Neurorestoratology.

 

 

Ziad.M.AL Zoubi (Jordan)

President of IANR;Director, Jordan Ortho & Spinal Centre;Founder, Jordan Spine Society; FounderPan Arab Spine Society; Chairman, Association for Spinal Cord Injury Care

 

The international associations and societies related to cell therapy research and treatment

Ziad Al-Zoubi

AbstractResearch on cell therapy for the treatment of chronic untreatable diseases is tremendous .extensive x-vivo, animal experiment and the clinical trials are now published in journals. Probably the chronic neuronal diseases like chronic spinal cord injuries are the most difficult to treat. Hundreds of clinical trials are running now in many centers all over the world , this interest in cell therapy raised many questions about the seriousness of this huge number of research work and this leads automatically to establish many research centers , societies, associations .etc

This lecture will discusse the need for some form of accreditation rules , classification of these centers, and groups of research centers to help the researchers and the demanding patients . 

 

 

Long-term Follow-up Observation on 24 Patients with Spinal Cord Injury Receiving Olfactory Ensheathing Cell Transplantation

He Xijing1Wang Dong 1Li Haopeng 1Xu Siyue 1Yang Pinglin 1

Description: 1Wang Guoyu 1Wu Fei 1Pei Leilei 2

1NO.2 Orthopedics Department, Second Affiliated Hospital, Medical School of Xi’an Jiaotong University, Xi’an, Shaanxi Province 710004, China.

2Statistical Learning and Research Department of Medical School of Xi’an Jiaotong University, Xi’an, Shaanxi Province 710004, China.

AbstractOlfactory ensheathing cell transplantation (OECT) has been used to treat patients with spinal cord injury (SCI). But it is still unclear about its long-term curative efficacy and safety. This study was retrospectively to analyze the long-term changes in sensory level, muscle strength, neural function and individual self-evaluations of 24 patients with SCI (male/female 20/4; average age 32.4 years, age range 19~45) who received OECT in our hospital from September 2005 to March 2010. The changes in neural function were estimated based on the ASIA scores. ANOVA was used to do statistical analysis. Successful transplantation and follow-up (averagely 3.2 years, range 0.5 to 5.2) were conducted and no apparent complications were found in all the 24 patients. Postoperatively, 9 patients with total paralysis showed the sensory level descended to 1-2 spinal segments below the SCI level, and 1 patient had no change; among the 13 patients with quadriplegia 11 presented with two-spinal-segment descending of sensory level, 2 with three-spinal-segment descending, especially 1 of the 2 patients showing an improvement of flexor function and the emergence of thumb long extensor dorsiflexion movement (muscle strength 2 degrees). No mass or cavity formation was detected at the sites of cell transplantation by MRI. The self-evaluations of 2 patients for OECT were excellent, 9 good, 12 poor, and 1 very poor. The excellent and good-evaluation rate was 50%. ANOVA showed there was no obviously difference in ASIA scores between before and after OECT (P<0.05). In short, the transplantation of olfactory ensheathing cells derived from allogeneic embryonic olfactory bulb induction is a safe therapy for spinal cord injury. But the long-term therapeutic effect of OECT on SCI is not perfect. This technique still needs further observation and exploration. 

Key wordsspinal cord injury; transplantation; olfactory ensheathing cells; efficacy evaluation

 

 

 

脊髓损伤嗅鞘细胞移植24例中期随访观察

贺西京,王栋,李浩鹏,王国毓,乔鸿飞

西安交通大学医学院第二附属医院骨二科

目的:了解脊髓损伤患者嗅鞘细胞移植后的中期随访结果,评价嗅鞘细胞移植治疗脊髓损伤的临床安全性及疗效。

方法:回顾性分析我院20059月至20103月共24例异体胚胎嗅球来源嗅鞘细胞移植治疗的临床病例的疗效,患者平均年龄32.4岁(19-45岁),其中男性20例,女性4例。四肢瘫13例,截瘫11例,不全瘫14例,全瘫10例。移植手术前后根据ASIA评分标准计算分值,取其平均数进行配对资料的t检验统计分析,P>0.05为有显著性差异。移植的嗅鞘细胞来源于引产胚胎嗅球,取材后培养7-10天进行移植,细胞浓度106。注射细胞前所有病例均进行脊髓损伤段瘢痕组织松解,,注射点选择在脊髓损伤区远近端约0.5cm处的脊髓后角处,进针深度约3mm,注射细胞量约40ul。术后常规处理,随访采用门诊预约的方式,每3月观察患者截瘫感觉平面的变化,截瘫平面下肌肉肌力的变化,以及患者对于治疗效果的评价,并应用ASIA评分了解神经功能变化情况,结果应用SPSS分析。

结果:患者手术均顺利,所有嗅鞘细胞移植后患者均得到随访,随访平均时间3.2年(0.5~5.2年)。9例全瘫患者术后感觉平面下降1-2个脊髓节段,运动未见变化;1例感觉平面未见变化。11例四肢瘫患者的感觉平面下降2个节段;2例患者下降3个节段,其中1例患者的屈指功能改进,并出现拇长伸肌的背伸运动,肌力为2级。所有患者经随访未发现明显的手术并发症,术后MRI检查未发现移植局部的包块形成或空洞。患者自身对其所获治疗效果评价优:2例,良:9例,可:12例,差:1例;优良率:50%ASIA评分比较手术前后对比未见明显差异(P>0.05)。

结论:应用胚胎嗅球来源嗅鞘细胞移植治疗脊髓损伤的方法较安全,移植后患者临床症状改善,但改善有限,需进一步观察及探索。

关键词:脊髓损伤;移植;胚胎;嗅鞘细胞;疗效评价。

 

 

 

Hari Shanker Sharma (Sweden)

President Elect of IANRPresident of GCNN

Laboratory of Cerebrovascular Research, Dept. of Surgical Science, Anesthesiology & Intensive Care Medicine, University Hospital, Uppsala University

 

Pharmacotherapy: Progress in Neurorestoratology

Hari S Sharma, Ph D, Dr Med Sci

Central nervous system (CNS) injury is caused by a variety of external and internal factors leading to serious mental and physical dysfunction [1-3]. The science of Neurorestoratologyestablished in recent years by Huang and his International group from Beijing, China focused on restoration of all kinds of mental and physical dysfunctions caused by disordersof the CNS [4]. Thus, CNS injuries caused by external factors e.g., trauma and/or neurodegenerative diseases i.e., Parkinson’s, Alzheimer’s, Huntington’s Diseases, Multiple sclerosis, stroke, ischemia, infarction or other kinds neurological injuries require extensive restoration using pharmacotherapy in combination to neuroregenerative approaches e.g., treatment with stem cells, neurorehabilitation including exercise and training as therapy in combination with other suitable therapeutic measures [1-5]. Thus, the science of Neurorestoratology combines all forms of physical, chemical and cellulartreatments to restore functions of the CNS in patients [4]. Our laboratory is engaged in neuroregenerative therapy in different animal models of CNS injuries [5-8]. Our observations shows that multiple combinations of neurotrophic factors derived from neurons, e.g., brain derived neurotrophic factor (BDNF), or glia derived neurotrophic factor (GDNF), nerve growth factor (NGF), ciliary neurotrophic factor (CNTF) when administered exogenously following CNS injury caused by trauma or hyperthermia induces remarkable restoration of neuronal, glial and endothelial cell structure and functions [1-3, 5-8]. However, other combination of neurotrophic factors is not that effective in identical situations. This suggests that suitable combination of neuroregenerative therapy using neurotrophic factors leads to marked neurorestoration. Interestingly, the therapeutic efficiency of these neurotrophic factors is further enhances when they are administered using nanowired technology [6]. However, nanowired drug delivery did not alter the fundamental principles of neurotrophic factor therapy. Thus, this combination of neurotrophicfactors that did not influence neurorestorationisstill not altered following their nanodrug delivery. However, nanowired drug delivery of neurotrophins that Inducesprofoundneurorestorationismark

edlyenhancedusing nano-drug delivery. The functional significance of neurorestorative therapy using neurotrophic factors with or without nanodrug delivery is discussed.

 

 

 

Description: Arthur M

Arthur M. Sherwood (USA)

Professor, Department of Physical Medicine and Rehabilitation, Baylor College of Medicine; Science and Technology Advisor, National Institute on Disability and Rehabilitation Research Department of Education

 

Monitoring and Neuromodulation of motor control after spinal cord injury

Arthur M. Sherwood1*, W. Barry McKay2, and Milan R. Dimitrijevic3

1Department of Physical Medicine and Rehabilitation and Research, Baylor College of Medicine, Houston;2The Shepherd Center;3Department of Physical Medicine and Rehabilitation and Research, Baylor College of Medicine, USA

The ability to reliably, objectively and quantitatively characterize motor control within the surviving, or pre-treatment spinal cord, and then to sensitively monitor changes brought by any intervention attempt is essential to the evaluation of protocols designed to ameliorate the consequences of spinal cord injury. This presentation will describe a method that measures the spinal motor output in the form of multiple-muscle surface-recorded electromyographic activity that is produced in response to a standard set of reflex and volitional activities attempted under controlled conditions.  Calculated from this recorded activity, selected parameters and indices are used to quantitatively describe residual motor control and intervention effects.  The theoretical basis and practical aspects of designing appropriate tasks, presenting them to test subjects, quantifying output, calculating indices, and interpreting results will be presented, with emphasis on the practical implementation in a clinical context. In addition to the objective quantification of reflex and volitional tasking, this measurement tool provides an opportunity to monitor neuromodulatory effects of unpatterned stimulation.  Presented here will be the effects of epidural or transcutaneous electrical stimulationof dorsal root afferents that appear as multisegmental, motor unit outputvarying according to the distribution and parameters of the stimulation. These output patterns, including particularly locomotor-like activity, provide evidence of the function of the “spinal brain”.

 

 

 

Functional Significance of Adult Neurogenesis in the Mammalian Brain

Kwok-Fai So

Department of Anatomy, The State Key Laboratory of Brain and Cognitive Science, The University of Hong Kong, Hong Kong SAR China; JNU-HKU Joint Laboratory of Brain Function and Health, Jinan University, Guangzhou, China

Functional neurons are generated from adult neural precursors throughout life in adult mammals. Adult neurogenesis has attracted a lot of interest in the past decade. Our laboratory focuses on the role of adult mammalian neurogenesis in the dentate gyrus of the hippocampus and from the subventricular zone of the lateral ventricle on sexual function and psychiatric condition including depression. Enhancing endogenous neurogenesis including proliferation and differentiation of new neurons by various treatments could be a useful approach in regenerative medicine in the injured brain and spinal cord.

 

 

 

A neonatal mouse SCI model for testing human stem cells including high throughput functional imaging of synaptic connections

Joel Glover

AbstractWe have established a model of SCI in the neonatal mouse that provides the opportunity to implant human stem cells of various types in a context of dynamic functional recovery where they can be assessed for survival, proliferation, differentiation, and functional integration.

The model involves a compression injury at thoracic levels followed by stem cell implantation and/or high-throughput functional imaging using calcium-mediated activity probes. In this model, functional deficits as assessed with behavioral tests are evident during the first day after injury and dramatic functional improvement occurs during the ensuing few days. During this period, it is possible to record synaptic activity in spinal neurons using calcium imaging such that descending inputs can be assessed above and below the lesion at different times during the recovery process. In this model we have begun to test the capacity for human fetal neural progenitor cells to survive and integrate into the spinal cord. So far we have found that these cells can survive for at least 15 days during which time they begin to differentiate and elaborate neurites. We are now testing whether they are able to receive inputs from specific descending pathways originating in the brain stem.

 

 

 

Stereotaxic implantation of Olfactory ensheathing cells OECsfor stroke patients

Woei-Cherng Shyu

Key wordsolfactory ensheathing cells (OECs), old stroke, early phase clinical trial, stem cells

Based on our previous preclinical study (Shyu WC, Journal of Clinical Investigation 2008; 118:2482–2495), we thus held the phase Ib/IIa clinical trial study. We will recruit 6 patients (between 35 and 70 years of age) who have suffered from old cerebral infarction over middle cerebral artery territory for over 6 months to 5 years with the severity measured by the National Institute of Health stroke scale (NIHSS) from 5 to 15 scales. Recruited patients should be received the endoscopic surgery for picking the olfactory mucosa 1 to 2 months before transplantation. The OECs will be cultured and expanded under the rule of GTP. Then, quality control of OECs should be done by immunohistochemical staining positive for GFAP, S100, and P75. Finally, we perform stereotaxic transplantation of the OECs (about 2 to 8 ´106 cells in saline) into the peri-infarcted area. All patients will be followed for one year. The primary outcome end points are set to analyze scores of the NIH-stroke scale (NIHSS), European stroke scale (ESS), and European stroke motor subscale (EMS). In addition, we also measure the quantitative results of diffusion tensor image (DTI) using MRI and motor evoke potential (MEP) by transcranial magnetic stimulation (TMS) as the secondary end point.

 

Muse cells, a novel type of adult human pluripotent stem cells that reside in mesenchymal tissues: their great possibility for regenerative medicine

Mari Dezawa

Department of Stem Cell Biology and Histology and Department of Anatomy and Anthropology, Tohoku University Graduate School of Medicine, Sendai, Japanmdezawa@med.tohoku.ac.jp

Since pluripotent stem cells are able to generate all kinds of ectodermal, mesodermal and endodermal cells, they are expected to be applicable to various kinds of diseases. While ES cells and iPS cells are well known pluripotent stem cells, they have risk of tumorigenicity. Adult stem cells are natural cells residing in our living body and normally do not show tumorigenic proliferation. However, they typically generate the cell types of the tissue in which they reside and thus the range of their differentiation capabilities is considered limited.

We newly found a unique type of stem cells which we named Multilineage differentiating Stress Enduring (Muse) cells (Kuroda et al., PNAS, 2010). They are adult stem cells that reside in adult human mesenchymal tissues and are pluripotent. They can be isolated as cells double positive for mesenchymal marker CD105 and human ES cell marker SSEA-3 from bone marrow, skin and fat tissues or from commercially available human cultured mesenchymal cells. Muse cells were found as stress tolerant cells, and express pluripotent stem cell markers, self-renew and generate cells representative of all three germ layers from a single cell. Most importantly, they do not show tumorigenic proliferation, a trait that is consistent with the fact that they reside in adult tissues. Furthermore, they are shown to migrate and home into damaged tissues when infused into peripheral blood. When human Muse cells are infused into tail vein of Nog-mouse suffering from spinal cord injury, fulminant hepatitis, diabetes mellitus and skin injury, human Muse cells integrated into those damaged tissues, differentiated into neuronal cells, hepatocytes, insulin-producing cells and keratinocytes, and finally contributed to tissue reconstruction.

Recently, we found that Muse cells are a primary source of iPS cells in human fibroblasts (Wakao et al., PNAS, 2011). When human fibroblasts were separated into Muse and non-Muse cells and transduced with Oct3/4, Sox2, Klf4, and c-Myc, iPS cells were generated exclusively from Muse cells, but never from non-Muse cells. Epigenetic alterations were not seen in non-Muse cells and some of the major pluripotency markers were not expressed for the entire period of generation, suggesting that Muse cells whose properties are already similar to that of iPS cells selectively become iPS cells, whereas the remaining cells make no contribution to the generation of iPS cells.

Thus, Muse cells will be beneficial for cell-based therapy and biomedical research.

 

 

 

Description: William Slikker

William Slikker (USA)

Director of the FDA’s National Center for Toxicological Research;Adjunct Professorships in the Departments of Pediatrics, and Pharmacology and Toxicology at the University of Arkansas for Medical Sciences

 

Pathways to Protection from Pediatric Anesthetics

W. Slikker, Jr., X. Zhang, F. Liu, S. Liu, X. Zou, N.V. Sadovova, R.L. Divine, T.A. Patterson, S.F. Ali, L. Guo, Q. Shi, D. Doerge, J.P. Hanig, M.G. Paule and C. Wang

National Center for Toxicological Research/FDA and Toxicologic Pathology Associates, Jefferson, AR, USA; Center for Drug Evaluation and Research/FDA, Rockville, MD, USA

In several animal models it has been shown that the developing brain is susceptible to anesthetic-induced injury.  The window of vulnerability to these neuronal effects of anesthetics is restricted to the period of rapid synaptogenesis, also known as the brain growth spurt. Similar dependencies on dose/duration of exposure and developmental stage are observed in both the non-human primate and rodent models for NMDA receptor-dependent anesthetics (e.g., ketamine). The duration of anesthesia needed to induce cell death as measured by minimal exposure requirements is similar (~ 4-6 hrs) for nonhuman primate and rodent brain cells in culture, and also in vivo in rodent and nonhuman primate models.  The susceptible stage or period of development has not been completely described, but in the nonhuman primate it begins somewhere before the last quarter of pregnancy and continues until shortly after birth. Behavioral studies in developing primates have confirmed functional deficits following neonatal ketamine-induced anesthesia as assessed by the NCTR Operant Test Battery. In rats previously exposed to ketamine, microPET imaging data have indicated enhanced 18F Annexin-V retention, a non-invasive marker of apoptosis. It has been postulated that up-regulation of the NR1 subunit of the N-methyl-D-aspartate receptor, a calcium channel regulator, may be an important first step in the pathway to anesthetic-induced neurotoxicity following exposure to NMDA antagonists. Both gene expression studies and NR1 antisense experiments have provided supportive evidence for NMDA receptor involvement in the neurotoxic pathway. Several recent studies have indicated that reduction of oxidative stress may protect the developing animal from anesthetic-induced brain cell death. Evidence for the role of oxidative stress in anesthetic-induced neurotoxicity has been generated in studies that apply oxidative stress blockers, including L-carnitine (mitochondrial protector) and melatonin in vivo and specific antioxidants in vitro including the superoxide dismutase mimetic, M40403 and the NOS inhibitor, 7-nitroindazole. Recent gene expression assessments indicate that genes in the oxidative stress pathway are altered by anesthetic treatment of developing animals. The effect of ISO/N2O on the uptake and retention of [18F]-DFNSH in the brains of different aged rats and the potential protective effect of acetyl-L-carnitine (ALC) on anesthetic-induced neuronal cell death were investigated using microPET imaging. On PND 7, rat pups were exposed to either a mixture of 70% N2O/30% oxygen plus 1% ISO for 8 hours with or without ALC, or to room air only (control). On PNDs 14, 21 and 28, [18F]-DFNSH (18.5 MBq) was injected i.p. and 30 minutes later microPET images were obtained over 90 minutes. In PND 14 rats the uptake of [18F]-DFNSH was significantly increased and the duration of tracer wash-out was prolonged in ISO/N2O-treated rats and ALC block this effect. The data of calcium imaging supports the hypothesis that continuously blocking the NMDA receptors by ketamine can cause compensatory up-regulation of NMDA receptors, which allows the accumulation of toxic levels of intracellular Ca2+ after ketamine withdrawal, subsequently may trigger apoptosis in neurons. Together, the application of omics approaches along with traditional toxicological endpoints indicates that oxidative stress plays a critical role in the susceptibility of the developing brain to anesthetics. Supported by NICHD, NTP/NIEHS and CDER and NCTR/FDA

 

 

Description: 200882113462330910

Zuo Luan(China)

Director, Department of Pediatrics, Navy General Hospital; Vice President of IANR; Vice Chairman, Stem Cell Engineering Committee, Chinese Medical Association Biomedical Engineering Socie

 

Clinical efficacy of the neural precursor cells transplantation to treat the severe visual impairment – a sequela of neonatal brain injury

Zuo Luan, Suqing Qu, Kan Du, Weipeng Liu, Yinxiang Yang, Zhaoyan Wang, Ying Cui1, Qingan Du

Department of Pediatrics, Navy General Hospital Beijing 100037, China

1. Postgraduate student of Soochow University

ObjectiveTo investigate the clinical efficacy of the neural precursor cells transplantation to treat the severe visual impairment – a sequela of neonatal brain injury.

Methods52 patients with cerebral injury and visual impairments caused by various reasons in our hospital out-patient department from May 2005 to Feb 2009 were selected and randomly divided into 2 groups: the treatment group (n=25, with the average age of 18 months) and the control group (n=27, with the average age of 19.5 months). There were no significant difference in the sex, age, cause of disease, type of cerebral injury and visual impairment degree between two groups. The treatment group received intraventricular transplantation of human neural stem cells and rehabilitation training. The control group received rehabilitation training only.

Results1 in 5 fundus abnormalities associated with blindness patients got light perception. The visual functions of 15/20 patients with normal fundus were improved 1 level or more. After 2-year follow up, the visual function of 3 paitents improved from level I to level II, 4 from level I to level III, 1 from level I to level IV, 2 from level II to level III, 3 from level II to level IV, 2 from level II to level V. The efficacy appeared on 60 days post transplantation in median and the effective rate is 64% in the treatment group. In the patients showed efficacy in the treatment group, 1 blindness patient got light perception. 5 (31.2% got level improvement, 10 patients 62.5% got more than level improvement.

In the control group, 4 patients with fundus abnormalities showed no improvement in the visual function. The visual function of 9 cases in the other 23 cases improved at least 1 level. After 2-year follow up, there was no patient whose visual function improved from blindness to level I, 2 from level I to level II, 1 from level I to level III, 4 form level II to level III, 1 from level II to level IV, 1 from level II to level V. The total effective rate is 33.33%. In the patients showed efficacy in the control group,, 6 patients (66.67% )improved level, 3( 33.33%) improved more than levels. The efficacy appeared on 365 days in median. Part of the patients underwent the functional Magnetic Resonance Imaging ( fMRI ) showed positive activation signals in occipital lobe, visual pathway and apical lobe After transplantation,

ConclusionNeural precursor cells transplantation is effective for the patients with severe visual impairment – a sequela of neonatal brain injury. NPCs transplantation showed significantly earlier improvement, higher improvement rate and degree in visual function compared with the traditional rehabilitation training.

Key wordsBrain injury; visual impairment; neural precursor cells; transplantation; children

 

 

 

Integrated Regenerative Therapy Program (IRTP) for management of Autism and other disorders

Yahia Yousif, Khaled Batterjee

Research Institute of Batterjee Medical College for science and TechnologySaudi Arabia

Background   Autism Spectrum Disorders (ASD) are a group of neurodevelopmental disorders their incidence reaching epidemic proportions, afflicting approximately 1 in 150 children and increasing dramatically allover the world. It reflects a whole-body process often involving gastrointestinal pathologies, immune dysregulation, mitochondrial dysfunction, gut infections, detoxification pathways and nutrient levels. Increased oxidative stress is reported and has both etiologic and clinical significance. Environmental pollutants especially aluminium and mercury, some food additives and excitotoxins, sensitivity of food components could play a major role. Cerebral hypoperfusion, especially of the temporal lobes, and hypoxia are very common findings in children with autism affecting up to 75% of patients. Cerebral vasculitis and inflammatory-related findings could contribute to the cerebral hypoperfusion. Several clinical studies documented improvements using mono-therapy programs such as supplements, diets, hyperbaric oxygen (HBOT) and stem cell therapy but few clinical trials showed the effects of compatible multi-therapy programs.  

ObjectiveTo establish integrated therapeutic program using compatible overlapping therapy methods to manage (ASD).

MethodIn this pilot clinical trial 10 diagnosed moderate to severe autistic male children (2-11 years) were admitted to the trial. The integrated therapy program consists of three main overlapping stages:

(A) Daily intake of special Intensive Nutritional Mixture (INM) for three months and continue till the end of the trial. (INM) was prepared in our center using natural food ingredients and tested for two years among autistic children before the trial begin. 10 days Antifungal course (nystatin or fluconazole) was applied for all patients.

(B) Hyperbaric Oxygen course using monoplace chamber and standard protocol of 40 sessions, 1.3 ATA, 24% Oxygen, 75 min/daily. The course was repeated three times after two weeks intervals before proceeding to the third stage. 

(C) Administration of Stem Cells: about 5 Mio allogeneic CD34+ umbilical cord cells and mesenchymal cells were daily infused intravenous in 4 day's protocol.

Other therapies, supplements and drugs used by individual patients before the trial were continued without changes.

Evaluation the effectiveness of stages and the total program: The Autism Treatment Evaluation Checklist (ATEC) was used to evaluate the trial. Both Parents and physician submitted a weekly report up day 0 of the trial. 

ResultThe primary results demonstrated promising findings up till now: Stage (A) showed significant and sustained mild to good improvements in 9/10 of patients. The best scores were reported for following categories of (ATEC): Language/ Communication: Follow commands, respond to order. Sociability: Eye contact, sharing, greeting, affection. Sensory/ Cognitive awareness: Responds, interest, attention. Health/ behavior: wet pants, constipation, hyperactivity, unhappiness, crying, limited diet. Stage (B): Improvements were much more significant scoring good to excellent improvements in all patients up the first week of treatment especially the categories as above. No deteriorations or side effects were reported during these two stages. Stage (C): only few patients complete this stage till now but they showed much more improvements expanding to other items of categories of (ATEC).  

ConclusionUnderstanding of the biochemical and ecological context of the autism epidemic moves us away from the medical paradigm toward a system approach that focuses on overlapping compatible integrated therapeutic program. Non invasive complementary therapeutic tools like (INM) and (HBOT) in combination with antifungal drugs, CD34+ and mesenchymal umbilical stem cells were noted to induce sustained significant improvements of (ASD) patients could be through synergistic effects in neurological and vascular brain structures, although the number of patients are far too low to draw a definite conclusions. We propose to conduct the study based on the experiences of our group in this field, as well as numerous mono-therapy studies and generated anecdotal evidences of nutritional therapy, (HBOT) and stem cell therapy. We believe that through development of a potent clinical study with appropriate endpoints, much will be learned about the multifaceted pathophysiology of (ASD) and other neurological or vascular disorders which could have pathological similarities with (ASD) such as vascular dementia, CP, stroke, trauma, Attention Deficit/ Hyperactivity Disorder (ADD/AHDH) and the integrated way of  their management.

Key WordsAutism, ASD, hyperbaric oxygen, stem cell therapy, nutritional therapy, antifungal, nystatin, fluconazole, attention deficit disorder, hyperactive disorder, ADD/AHDH, diabetic neuropathy, CP, stroke, vascular dementia

 

 

 

Description: scan0002Alok Sharma (India)

Neurosurgeon ,Professor & Head,Department of Neurosurgery ,the LTMG Hospital & LTM Medical College, Mumbai

Director, NeuroGen Brain & Spine Institute in Chembur Consultant Neurosurgeon ,the Fortis Hospital, Mulund

 

Clinical results of autologous bone marrow derived adult stem cell transplantation in muscular dystrophy

Muscular Dystrophy is a genetic disorder with no definite cure available. A study was carried out on one hundred and fifty patients suffering from Muscular Dystrophy .Out of one hundred and fifty patients, 125 were DMD (Duchenne Muscular Dystrophy)type , 20 were LGMD(Limb Girdle Muscular Dystrophy ) and 5 of them were BMD (Becker’s Muscular Dystrophy)variant. They were administered autologous bone marrow derived mononuclear cells intrathecally and intra muscularly at the motor points of the antigravity weak muscles. Assessment after transplantation showed neurological improvements in trunk muscle strength, limb strength on Manual Muscle Testing (MMT), with Gait improvements  and a shift on assessment scales such as FIM ; Brooke and Vignos scale. Further, Imaging and Electrophysiological studies also showed significant changes in selective cases. On an average follow up of 12 months ± 1 month, overall 87% muscular dystrophy cases showed subjective and functional improvements , with 3 of them also showing changes of muscle regeneration on MRI and 9 showed improved muscle electrical activity on EMG. On comparison of the previous EMG’s with a year later follow up study , it was confirmed that the interference pattern in the muscles, that were injected with mononuclear cells , had improved thereby confirming increase in muscle strength and activity. 53% patients showed increase in trunk muscle strength , 48% showed increase upper limb strength , 59 % showed increased lower limb strength and about 10 % showed improved Gait. Also the clinical finding were consistent with the electro diagnostic results , thereby confirming halt in the progression of the disorder and also bringing about improvement in clinical condition of the patients. No significant adverse events were noted. The results show that this treatment is safe, efficacious and also improves the quality of life of patients suffering from Muscular Dystrophy.

Keywords: Autologous, Bone Marrow,  Mononuclear cells,  Muscular Dystrophy, Motor Points, Quality of life.

 

 

 

Description: GeoffGeoffrey RaismanUK

Honarary President of IANR for life.

Professor of Neural Regeneration,University College London Director of the Spinal Repair Unit,the Institute of Neurology, Queen Square.

 

 

Repair of Spinal Injury: Caution and Hope

Geoffrey Raisman,University College London

 It is a great honour and a great pleasure to welcome this distinguished gathering.

What thoughts can I – as a scientist –offer to congratulate and to encourage this international assemblage of pioneers here in Xian?

As a scientist, I seek to consider two questions:

Why do we think of transplanting cells? And:

Why is any more science needed?

Underlying our optimism is the concept that the nerve cells and nerve fibres of the adult brain and spinal cord are alive.  And that they retain throughout life the capacity and the potential for new growth, and to establish new connections and the functions that go with them.

We could call it the “Theory of Continual Neuronal Growth.”

This is possible because all the genes we use to direct the development of the nervous system are still there in the adult.  Can they not be active in the adult too?

We could call this theory the “The Potential of Continual Genetic Recapitulation.”

The nervous system functions because the nerve fibres make specific patterns of connections.  It follows that re-establishment of lost connections is the most logical basis for restoration of lost functions.

If we consider the “Theory of Continual Neuronal Growth” and “The Potential of Continual Genetic Recapitulation” then the problem for repair of the brain and spinal cord is the re-establishment of pathways that can lead damaged nerve fibres to regenerate to their original targets.

I call this “The Pathway Hypothesis.”

Why use olfactory ensheathing cells for repair?

Because the olfactory system is the only part of the central nervous system which can regenerate its connections. Therefore its pathway cells can re-lay a damaged pathway, and open the door into the CNS.  By transplanting them to other regions we can – at least in rat models – provide cells which can restore pathways, induce regeneration, and restore function in areas which do not show regeneration after injury.

 And always remember there may be other potential pathway cells, as yet undiscovered.

Our team has two goals:

Firstly, to identify a source of reparative cells in man.

Secondly, to devise materials and instrumentation to introduce them into human spinal cord injuries.

------ Our field holds great promise.  Therefore we need extra special caution.

 Spinal cord injury is one of the most devastating, life-impoverishing conditions that man can experience.  The patients are desperate.  The sentence is irrevocable, and life-long.  Their relatives, friends and loved ones are desperate.  We have to be a thousand-fold careful not to mislead them, not – however unconsciously – to exploit their suffering for our benefits.

We do not understand the nature of spinal cord injury.  We certainly do not understand a cure.  But they will look to every word we say and read into it a solution to their unhappiness.

None of the general public, very few of the press, and few of the medical profession know that almost half of paralysed patients will walk again without any intervention in the spinal cord.  They are astounded that rats recover again.  To them these facts are peddled as evidence of some pretended cure.  Quite a few years ago a colleague calculated that there were even then more than a hundred different ways of curing spinal cord injury in rats.  The press regularly reports new breakthroughs.  So why are people still in wheelchairs?

Where patients show improvement – either spontaneous or after intensive physio- and rehabilitation therapy – which are of immense benefit to quality of life - we must separate these benefits from the interventions we are trying out.

Operating on the spinal cord is a relatively new and infrequent approach to repair.  In general, only minor

benefits are recorded.  What are these benefits due to?  Untethering?  Re-vascularisation? Re-myelination?  Growth factors secreted by transplanted cells?

And plasticity.  This is a hardly understood phenomenon.  When I introduced the term in 1969 I simply meant the formation of new connections after injury.  But this was an automatic process.  We now know that new connections form both above and below spinal cord injuries.  But why?  What determines them?  What decides what new patterns are formed?  Can we control them?  Can they, like normal connections in development, be trained?  Are they beneficial?  Or do they cause problems?  May they cause spasticity?  Pain?  Abnormal sensations?  Bladder  detrusor dyssyngergia?  Autonomic dysreflexia?

Plasticity is a pointer to the “Theory of Continual Neuronal Growth” and “The Potential of Continual Genetic Recapitulation.”

But if we are to benefit from plasticity, we need to know what causes it, how it is controlled, how we can use it.  And I believe that the answer lies not in neurons but in the pathway cells, in olfactory ensheathing cells and in astrocytes.

------The great mantra of our day is stem cells.  Stem cells have a meaning for governments – they will bring prosperity.  For companies a patent-protected cell in a bottle will generate fortunes on the stock exchange.  They will sell endless articles for the press, endless programmes for the media.  New scientific societies are formed.  New careers develop.  A true bonanza.

But what are stem cells?  Do we need no explanations of these miracles?  Can one human embryo give cells which will do all these things?  Can we avoid the immune barrier?  Will the cells, which are supposed to have endless potential for division be stopped before they form a tumour?  Will the cells that can turn into the 200 odd different types of adult cells turn only into the ones we want?  And if they did, will they find their way to the injury or tissue to be repaired and be accepted and incorporate themselves anatomically and functionally into it?

------Discovery begins with the statement that we don’t know.  The statement that we do know prevents advance.  Let us accept that we do not know how to cure spinal cord injury.  We have a few clues, minor.

What is needed?

First, I believe that the science base can give clues, directions among the many alternative possibilities.  Those who oppose animal experimentation on ethical grounds, or those who think money spent on science is wasted, should realise that the alternative is to experiment on people.  It’s a choice.

Second, from the few patients who are being treated world wide, we should collect clinical evidence.  Each trial is a mine of information, but that information has to be extracted from the mine.  A full, longitudinal neurological evaluation, before and after by independent observers would be immensely valuable.  Intensive pre-interventive physiotherapy should exclude that any further benefits can be obtained before our planned intervention.

And Thirdly, maybe it is time to evaluate the almost universal practice of vertebral carpentry.  The remaining nerve fibres are microscopically small, but the messages they carry decide the patient’s future life.  Their location is invisible to the surgeon.  They are finer and more delicate than the finest threads of silk.  The manipulations needed to re-align and screw and cage vertebrae are physically forceful.  Screwing vertebrae saves money and beds.  It gets the patient up and mobile quickly.  Spinal injured patients are subject to postural hypotension.  Does an early the upright posture imperil the tenuous blood supply of the few remaining spinal cord fibres?  Those few remaining fibres are vital to any benefit the patient has.  Can these interventions do as much to harm them as to protect them?

------The present is the threshold of the future.

We have overcome the idea that nothing can be done.

 But we still do not know what is to be done.

Don’t let’s lose credibility by responding to patient, press, government, or career pressures.  Or the lure of wealth.

 We alone are responsible for what we do.

Let’s do it wisely.

And for the good of our fellow human beings.

We have set our sails, and we travel into an unknown ocean.  We carry with us a cargo which is as fragile as it is precious -

That cargo is Hope.

 

 

 

Central Nervous System Injury and Repair. Role of Nanomedicine, Stem Cells, Antibodies and other Therapeutic agents

Hari S Sharma, Aruna Sharma

Laboratory of Cerebrovascular Research, Dept. of Surgical Science, Anesthesiology & Intensive Care Medicine, University Hospital, Uppsala University

Pathophysiology of the Central nervous system (CNS) injury is complex and involves damage to neuronal, glial and endothelial cells leading to brain dysfunction [1-3]. Studies carried out in our laboratory since 1977 shows that disruption of the blood-brain barrier (BBB) to proteins play crucial roles in precipitating brain edema formation and cell damage [3-6]. Thus, restoration of the BBB with drugs, antibodies, stem cells or other therapeutic agents are needed to induce neuroprotection or neurorepair in the CNS following noxious insults. Recently, it appears that nano delivery of stem cells, antibodies or therapeutic agents leads to enhancement of neuroprotection and cell repair [1-4]. Using animal models of CNS injury including traumatic, ischemic, hyperthermic, or following psychostimulants abuse we have demonstrated breakdown of the BBB and brain edema formation that is instrumental for brain damage [4-6]. Using antibodies to serotonin, tumor necrosis factor-alpha (TNF-a) and dynorphin A (Dyn-A) either alone or in combination leads to remarkable neuroprotection in spinal cord injury (SCI). Furthermore, nanowired delivery of these antibodies leads to long-term neuroprotection in SCI. Our experiments also showed that hyperthermia or brain injuries when inflicted in animals with hypertension or diabetes, the pathophysiology of brain damage is exacerbated. In such situations, nanowired delivery of mesenchymal stem cells is able to induce profound neuroprotection whereas other drugs or therapeutic agents did not induce remarkable brain protection. In hyperthermia, cerebrolysin, a mixture of various neurotrophic factors and peptide fragments showed enhanced neuroprotection when administered using nanodrug delivery. On the other hand, normal compound alonewas limited in inducing neuroprotection in hyperthermia. These observations suggests that nanodelivery of stem cells, antibodies and other therapeutic agents could results in superior neuroprotectionfollowing CNS injury leading to neurorestoration in a more effective way. The functional significance of these findings in relation to neurorestoratology will be discussed.

 

 

 

Andrey BryukhovetskiyRussia

Description: IMG_7943kHe retired from the position of Chief Neurologist of the Russian Navy as colonel of the Medical Naval Service and continued his clinical and research work in private hospital “NeuroVita”. He pursues treatment of neurological disorders through stem cells for 25 years. In 2005-2009 he headed the Department of Cell Reparative Medicine of the Russian State Medical University.

Post-Genome Technologies in Neurorestoratology: from Mapping and Profiling of Stem Cell Proteome to the Development of Personalized Cell Preparations for Regenerative Therapy of Neural Disorders

Andrey Bryukhoveskiy

National Institute of Regenerative Medicine,

NeuroVita Clinic of Restorative Interventional Neurology and Therapy ,Moscow, Russia.

The idea that decoding the structure of genetic defect of pathological neural cells (NCs) in major neural disorders (NDs) will lead to their efficient treatment has long prevailed in classical neurology. Successfully accomplished The Human Genome Project demonstrated that decoding genome of a somatic cell (SomC) did not approximate understanding of pathogenesis and treatment of incurable human diseases (cancer, diabetes, SCI). Consequently, the sciences involved into restoration of neural tissue (NT) place their hopes on the development of post-genomic technologies, such as proteomics, metabolomics, secretomics of NCs etc. In 2010 a new global project, the Human Proteome Project was initiated, to map the protein based molecular architecture of human body and answer fundamental questions of developmental biology and molecular medicine.

Presumably, it is methodologically incorrect to view cell proteome as cataloguing proteins in specific chromosomes, even though associated with specific NDs. First, such “accounting” approach to protein evaluation is hardly justified for lack of knowledge, as by now science has only gathered evidence on about 2000 high copy number and medium copy number proteins and almost nothing about low copy number and very low copy proteins. Second, all proteins of cell proteome present on the one hand a high-speed information protein network, while on the other a global information database the elements of which have complicated information relationship. This information database forms karyotype and phenotype of a SomC and its proteome presents a fundamental characteristic of the information flow issued by protein pathways that interconnect extracellular environment with cell gene transcription control. This information can be either the cause or the effect of ND processes. The relations of genome and proteome are still unclear. Only 1.5% of genome in the somatic cell nucleus is responsible for the formation of a whole cellular protein network, the rest parts of genome present a regulatory software to provide protein synthesis and a so-called junk DNA the role of which is not determined yet. Thus, cell proteome is to be studied as information relationship between information structure of a cell and its microenvironment.  

From the point of view of information approach the genome is the most stable structure to support a karyotype and species of a healthy cell (HC) of nervous tissue (NT). Transcriptome is a more flexible cell structure, and the most flexible is proteome which still depends on microenvironment, active methylation processes, histone modification and iRNA transformation. Proteome of a HC of NT is quite stable and strictly correlates with the phase of a cell cycle (CC), differentiation stage, cell effector functions (EF). In different tumors of central nervous system (CNS) aneuploidy and chromosome mutations of tumor cells (TCs) make genome the most unstable structural element leading to transitory disorders of transcriptome that change cell karyotype used to diagnose TC phenotype. Yet proteome of a TC is a rather stable information structure that characterizes tumor karyotype, phenotype and EF (proliferation, angiogenesis, migration etc). In degenerative diseases point chromosome mutations of NCs lead to CC disorder and trigger specific EFs (autophagy, apoptosis, atrophy) conditioned by accumulation of various pathogenic proteins in cell cytoplasm (b-amyloid in Alzheimer’s disease, Levi bodies in Parkinson’s disease and various dementias, etc) and excitotoxic effect on neurons.

Microarray analysis (MAA) of transcriptome and mass-spectrometry (MS) of proteome of various cells demonstrated that correlation of protein profiles of the components of cellular protein network is observed only in HCs and is hardly present in pathological cells. Normalized signal intensity (NSI) of cell transcriptome and proteome proteins revealed several patterns: 1. NSI structure and parameters of transcriptome and proteome proteins of differentiated NCs, SCs and cells of specific (even pathological) line differ only quantitatively and matrix of distinction includes from 30 to 40 of the same proteins with varying NSI. 2. From 70 to 95% out of 907 studied proteins of proteomic profile (PP) in CNS cancer stem cells differ from the proteins of healthy SCs, and similarity matrix makes only 48 proteins (5.4%). Depending on malignancy this indication of distinction matrix varies from 45 to 96.3%. In other words, proteome network of cancer SCs displays information protein incompatibility with proteome network of healthy SCs. Attempting to preserve its species identity and relieve itself from foreign proteins, cancer SCs get rid of them in a primitive way by mitosis. However, critical percentage (over 50%) of non-species proteins does not allow for preservation of the species through cell division thus conditioning uncontrolled mitoses in cancer SCs. In degenerative disease (Parkinson’s disease) matrix of distinction does not exceed 30%, while the MAA results have no correlations at all.          

Based on PP of NT cells, we offered a novel approach to develop personalized cell preparations (PCP) for neurorestoratology. To obtain PCP for NT restoration of a specific patient healthy hematopoietic, mesenchymal or neural SCs labeled with specific antibodies (SAB) with magnetic beads are isolated from bone marrow sample, or leukoconcentrate of peripheral blood or resuspended olfactory sheath of the patient’s nose, respectively. Similarly, cancer SCs or atrophic NCs, also labeled with magnetic beads SAB are isolated from the tumor sample or specialized pathological NCs. MAA of miRNA is done and the result is processed with standard software Affimetrix Gene Chip. Tryptic peptides of healthy and cancer SCs are analyzed on a flow cytometer combined with MS. Obtained MS results are standardized with software Proteome Discoverer 1/0 (Thermo).

The MAA and MS data are brought to NSI. To exclude the noise of dynamic changes in cell protein network on healthy SC NSI PP, the values of NSI of proteins received in MAA and values of NSI or proteins of cell cytoskeleton are subtracted from the database of MS healthy SC proteins. Then the NSI PP of examined cell systems is compared and the difference between the NSI of specific healthy SCs proteins and the NSI of specific cancer SCs (matrix of distinction) is detected. The results of maximal difference between NSI of healthy and cancer SCs detected one or several (but no more than 4) key proteins of healthy SC PP. According to the detected key proteins one or several regulatory proteins or a chemical compound is chosen from the database, that have a potential for inductive effect on key protein changing NSI PP of the latter in a personalized fashion consistent with cancer SCs PP. Provisionally selected healthy autologous and/or allogeneic HLA-haploidentic multipotent SCs and/or progenitors are cultured with one or several regulatory proteins or chemical agents to obtain required PCP.

One of the principles of modification (reprogramming) of NSI PP of healthy SC proteins is the principle of approximation or identity of key proteins, when the selected regulatory protein(s) or chemical agent(s) modify the profile of healthy SCs approaching its values to those of cancer SCs key proteins, that is upregulating or downregulating it to the values of key proteins NSI in cancer SCs or slightly higher than in cancer CSs. Other principle of reprogramming NSI protein proteome profile of healthy SCs is the principle of inversion or suppression of key proteins, when regulatory protein(s) or chemical agent(s) modify the healthy SC PP by maximal downregulation (or blocking) of key proteins in a healthy SC which are maximally upregulated in cancer SCs, that is, reduce it to the value (or slightly lower) of key proteins NSI in cancer SCs. To enhance anticancerous action combinations are also possible. Healthy SCs are induced by addition of appropriate regulatory protein(s) or chemical agent(s) during culturing and further washing. The PCP is administered intravenously, intracerebrally or intramedullarly.

The development of PCP on the basis of transcriptome and proteome profiling of healthy SCs and pathological cells of the patient can become a universal method for personalized therapy of nervous disorders in the near future.

 

 

 

Dafin F. Muresanu (Romania)

Professor of Romanian CFR Medical UniversityHead of Department of Neurology of afflicated hospitalAssociate Dean of "Iuliu Hatieganu" Universitymembers of the Romanian Academy of Medical Sciences

The crosstalk between vascular and degenerative mechanism in neurocognitive disorders. Is there a place for endogenous neurogenesis?

Dafin F. Muresanu

Chairman Department of Neurosciences

University of Medicine and Pharmacy “Iuliu Hatieganu”, Cluj -Napoca, Romania

There is increasing evidence that cerebrovascular dysfunction plays a role in vascular causes of cognitive impairment (VCI) and also in Alzheimer’s disease (AD). Coexistence of ischemic and neurodegenerative pathology was found to have a profound impact on the expression of the dementia, suggesting reciprocal interactions.

This presentation will highlight some important molecular mechanisms involved in the complexity of vascular changes underlying pathological developments in Alzheimer’s disease and vascular dementia. New data regarding the role of endogenous neurogenesis in this disorders will be presented.

Both A-beta and vascular risk factors target the structure and function of cerebrovascular cells, glia, and neurons (neurovascular unit), resulting in neurovascular dysfunction. As a general feature, coexisting cerebrovascular disease or incident ischemic lesions may shorten the preclinical stage of AD and accelerate disease progression.

Vascular dementia is a heterogeneous cluster of different syndromes and disorders with cognitive deficit, arising from a cerebrovascular disease as a common feature. Entities do not share aetiologies, mechanisms, clinical features, evolution or treatment. However, there is a tendency to define this entity as a distinct type of dementia with clinical and pathophysiological specificities.

Most common members of this group are: multi-infarct dementia, lacunar state, single strategically-placed infarct, post-stroke cognitive deterioration, Binswanger’s disease, genetic forms (e.g. CADASIL), hypoxic-ischemic-encephalopathy, Alzheimer’s disease with cerebrovascular disease, intracerebral and subarachnoid haemorrhage with cognitive impairment.

Treatment of broad dementia spectrum disorders is a challenging issue. A potential chance, beyond identification and treatment of risk factors, might be the use of pleiotropic and multimodal endogenous like molecules.

 

 

Description: Wang Dajue1

Dajue Wang(UK)

Honorary Visiting Consultant, Midlands Centre  for Spinal Injuries, Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, UK Advisor, China RehabilitationResearch Centre, Beijing, Project Advisor, Spinal Cord Repair, Institute of Neurosciences, Beijing

 

Cognitive Neural Rehabilitation

Dajue Wang

Background Cognitive neural impairment occurs in all ages from childhood to the seniles. Their causes vary considerably from cerebral palsy to Alzheimer’s Disease. In stroke and brain injury, the maximum damages have already been done during the accident and become more or less stable after the subacute stage. The management of cognitive impairment in these accidents is by and large rehabilitative. However, in age-related lesions, the impairment is slowly progressive. Hence, its management is not only rehabilitative but also has preventative (both primary and secondary) and therapeutic implications. In these lesions, if cognitive impairments can be detected and dealt with early, further progress may be prevented, slowed down and some of the existing problems reversed. All these effects are based on neural plasticity which declines with age. Whatever the cause of cognitive impairment, they share some common features that are the focus of discussion of this section. 

Cognition is occupying more and more centre stage in neuro-science and neuro-rehabilitation for following reasons.

1. Increasingly long life expectancy associated with a high incidence of cognitive impairments has made the study of the problem a matter of some urgency.

2. The role of physical medicine has been well established whilst cognition is yet to be fully recognised and understood. Weight is shifting to cognitive rehabilitation, particulary in researches, without which neural rehabilitation process in not complete.

3.  Advanced molecular biology since discovery of DNA structure offers deep insight into almost every molecule, its structure, composition and behaviour.

4.  New functional imaging technologies like functional magnetic resonance imaging (fMRI), positron emission tomography (PET), event-related potentials (ERP) and magneto-encephalography (MEG) allow scientists to visualise this difficult aspect of neuroscience and psychology in vivo and in dynamics.

SummaryCognition impairment has posed as a huge challenge to the society as the population is ageing, particularly in the developed world. Although difficult cases should be left for the specialists like psychologists and neurologists, the general medical profession or even the society in general need to be familiar with basic knowledge and skills in dealing with its mild form. Obviously, this short note is not for acquiring in-depth knowledge but for drawing attention to the problem. For this purpose, reading the recommended books below is advisable. From there, readers can expand their own references. Fishing out relevant references from an ocean of journal articles is very difficult and extremely time-consuming.

Recommended further reading

1. Raskin SA. Neuroplasticity and rehabilitation. The Guilford Press, New York, London 2011; pp351.

2. Stuss DT, Wincour G, Robertson IH. Cognitive neurorehabilitation. Cambridge University Press 2008; 606.

3. Cabeza R, Kingstone A. Handbook of functional neuroimaging of cognition. The MIT Press, Massachusetts, London 2001; 410.

 

 

 

Description: Giovanni TosiGiovanni Tosi (Italy)

Pharmaceutical Technology  researcher,the University of Modena and Reggio Emilia;Coordinator of "Applied Technology" curricula for PhD school in Health Products;member of Instruments Commission of Dep.Pharm.Sci.,Representative of the Dep.Pharm.Sci

Nanomedicine and Central Nervous System: the application, the perspectives and the future

G. Tosi*, B. Ruozi*, D. Belletti*, A. Vilella°, M. Zoli°, A.M. Grabruker§, F. Forni*, M.A. Vandelli*

*Department of Pharmaceutical Sciences, University of Modena and Reggio Emilia, Italy

°Department of Biomedical Sciences, University of Modena and Reggio Emilia, Italy

§Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, US

In the last years, the application of "nanotechnology “to the field of “medicine” surely represented the most innovative strategy to cop_20e with diseases and it could be named as nanomedicine applied to difficult-to-treat diseases.

As known, in this field of research, the most important goal to be reached is an increase in selectivity and specificity of drug action. Several results with stimulating findings in preclinical or clinical phases have been reached by using nanocarriers, delivering agents to targeted pathologies, and among them, it is known that neuro-pathologies represent a stimulating issue. In fact, the pharmaceutical treatment of Central Nervous System (CNS) disorders is the second largest area of therapy, following cardiovascular diseases. Nowadays, non-invasive drug delivery systems for CNS are actively studied. In fact, the development of new delivery systems (nanoparticles and liposomes) started with the discovery that properly surface-engineered colloidal vectors, with a diameter around 200 nm, were shown to be able to cross the Blood-Brain Barrier without apparent damage, and to deliver drugs or genetic materials into the brain. During this talk, an overview will be presented considering the most recent literature results of nanomedicine applied to brain diseases, carried out with all the most popular kinds of nanoparticulate systems, focusing in particular on immune-nanoparticles and peptide-decorated nanosystems able to target the CNS, with in vivo and in vitro evidences investigating the pathway for BBB crossing and CNS localization of engineered nanoparticles. The brain localization and the multi-modal pathways for BBB crossing highlighted the endocytosis as preferential pathway; moveover, in vitro test on hippocampal neurons showed the presence of cell-to-cell transport of nanoparticles.

 

 

 

Description: Foto MOVIGLIA

Gustavo Moviglia (Argentina)

Vice Presiden of professional Committee of IANRDirector of the Centre for the Investigation in Tissue Engineering and Cellular Therapy (in Spanish, CIITT) in Buenos Aires, Argentina

 

Four Essential Aspects to Procure the Complente Recovery of cSCI Patients

cSCI patients have not an appropriate vascularization of the damaged area, neither the Spinal Cord distal segment that, as consequence of the lack of brain connections, is also atrophied. The activity of pro repair inflammatory activity has disappeared. Conversely, there is a chronic inflammation that has generated an extracellular matrix which prevents repair. Stem Cells are not attracted to the injured area. The brain cortex disrupted the normal synapses network (engram) that organize appropriated muscle movements and spatial recognition of sensation originated in the affected area and down of that site.

The discontinuity of central nerve pathways and the subsequent new engram generated thereafter are Responsibly for

1. - Perception of analgesic and dysestesic skin areas

2. – Experience of paresis and paralysis, pathologic reflexes and so called spontaneous movements.

3. - Autonomic Nervous Dysfunction in the somatic territories innervated by the lesion site and below (dysautonomy);

Any therapeutic aproach maigth contemplate all thes facts to be structural and functional effective. Different strategies are presented in this lecture.

 

 

 

Development of an International Accreditation System for Stem Cell-Based Therapies

Adeeb AlZoubi1,2 , David Audley3, Mohammed El-Khateeb4,5, Bellur Prabhakar6, Mark Holterman2,

Ziad AlZoubi7, Emad Jafar7, Mohammad Shahin7, Feras Twal1, Rula Al-Azzeh1, Sameh Al-Bakheet1, Gigi Sia1, Farah Khalifeh1, Bahar Barzangy1, Suzana Dwas1, Mahasen Zalloum1, Samah AlZoubi1, Maen Abbasi1

1 Stem Cells of Arabia, Amman, Jordan

2 Department of Surgery, University of Illinois College of Medicine in Peoria, Peoria, IL, USA

3 International Cellular Medicine Society, Salem, OR, USA

4 Department of Pathology, Faculty of Medicine, University of Jordan, Amman, Jordan

5 National Center for Diabetes, Endocrinology and Genetics, Amman, Jordan

6 Department of Microbiology and Immunology, College of Medicine, University of Illinois, Chicago, USA

7 Department of Neurorestoratology, Jordan Orthopedic and Spine Center, Amman, Jordan

The fast advancing field of stem cell-based therapy is currently affecting vast majority of medical practices worldwide. With the exception of hematological malignancies, to date, there are no clear rules and guidelines which govern the utilization of stem cells in clinical practice. This is mainly due to the fast evolving nature of this new and exciting field of medicine, which limits the ability of governmental agencies from following up with the latest discoveries and advancements in stem cell research. One of the most challenging phases of biomedical research is to translate the available scientific findings from research bench to applicable clinical practice in order to serve the increasing demands of patients. This is most evident in the field of stem cell research, where there is an apparent lack of coherent and standard rules and guidelines that can be applied to regulate stem cell-based therapies in an acceptable international format. Classical biomedical research approach requires extensive, long, and exhaustive research efforts, which may take up to fifteen years before implementation in clinical practices. Additionally, there must be abundance of long term funding in order to carry out all the required steps from basic research to all three phases of clinical trials. This is rather difficult when it comes to stem cell-based therapies since there is little interest of biopharmaceutical industries due to the limited profitability of this type of practice. However, pressuring demands from patients for availability of treatments in shorter periods of time dictate formulating a more realistic approach in a timely manner. This approach must guarantee the delivery of high quality treatments to patients without compromising patient safety and authenticity of results.

A reliable stem cell-based therapy approach should include defining types and sources of stem cells, methods of stem cell collection and handling in the laboratory, and methods of transplantation of prepared cell populations under acceptable medical practice. In order to fulfill these three requirements, the team responsible for executing stem cell-based therapy protocols should guarantee the preparation and delivery of acceptable cellular products by authorized personnel in a licensed facility by utilizing well known and published procedures.

We, at Stem Cells of Arabia (SCA) in Amman, Jordan, and in collaboration with the International Cellular Medicine Society (ICMS), College of Medicine at the University of Illinois, Faculty of Medicine at the University of Jordan, National Center for Diabetes, Endocrinology and Genetics in Jordan, and Jordan Orthopedic and Spine Center, have formulated a new system for governance of high quality cell-based therapies. This system governs the utilization of autologous adult stem cells as source of cells, preparation of these cells using internationally accredited methods, and transplantation of prepared cells into the patient by acceptable and accredited medical procedures. To accomplish these objectives, our system consists of three accreditation parts: (1) accreditation of standard operating procedures (SOPs) (by the Institutional Review Board (IRB) of ICMS) that define patient enrolment and follow up, source and type of stem cells, methods of collection, manipulation, and transplantation of prepared cells into the patient, (2) accreditation of personnel involved in performing the above SOPs, which includes laboratory personnel (scientists, researchers, stem cell processing specialists, and quality control officers), physicians, nurses and other medical assistants involved in the procedure, and (3) accreditation of the facility where the SOPs are to be carried out, which must be a licensed institution by the appropriate governmental facility in the country where the procedure is to be carried out.

We believe this system can be applied internationally and in accordance with local rules and guidelines in the country where the procedures are to be performed. Although the current accreditation system is limited to the use of un-manipulated autologous stem cells in a safe manner, the system can be modified and extended to include other types of stem cells in different settings or formats.

 

 

 

Coding and traceability of Cell and Tissue products in Iran

Seyed Hassan EmamiRazavi*1; BabakArjmand1,2; HamidrezaAghayan1,2;

HooshangSaberi1; Abbas Norouzi-Javidan1

1Brain and Spinal Injury Repair Research Center / Tehran University of Medical Sciences

2Endocrinology and Metabolism Research Center / Tehran University of Medical Sciences

ObjectivesIn recent years, like many other countries in the world, modern cell therapy has been started in Iran. Furthermore, Iran has a leadership role in stem cell research and therapy among the middle eastern Muslim countries. Autologous Schwann cell transplantation for spinal cord injury, Mesenchymal stem cell transplantation for multiple sclerosis, cirrhosis, diabetes and myocardial regeneration, and hematopoietic fetal stem cell transplantation for diabetes, cirrhosis and multiple sclerosis are prominent examples of current clinical trials. These trials are generally regulated by scientific and ethical committees of medical universities but two of them have been registered in ministry of health (as national projects). Legal framework for cell and tissue research and therapy is based on the ‘‘Deceased or Brain dead patient organ transplantation’’ act (passed in 2000). There was no specific regulatory oversight for cell and tissue research and therapy by the national health authority till two years ago, that a new legislation was established to supervise the manufacturing of cell and tissue products as a basic and minimal safety standard for cell therapy centers while, cell manufacturing centers have established their own quality policies that have been referred to basic and general quality standards (cGMP, cGTP, and GLP) without any correlation to others.

Coding and traceabilityThe importance of effective coding, documentation, and traceability in safety and quality assurance of tissue and cell products is not negligible. Despite the lack of national authorization of coding, each cell manufacturing center has understood the importance of coding and traceability in tracking adverse events and reactions related to biologic products. According to these concerns some of them have defined a method in their SOPs for tracking all reported events from the donor to the recipient, and vice versa just inside their organization.

ConclusionsIn order to achieve the higher level of safety the authors recommend that a more specialized national standard for cell therapy should be established by the government. We also believe that implementation of some general quality managementsystem based on the ISO 9001 and ISO13485 can improve safety of cell based products. Additionally, we need to make a unique system to harmonize coding and traceability in the country and also in the region.

KeywordsCell therapy . Coding . Traceability

 

 

 

The Long-term outcomes for patients with sequela of stroke through multiple kinds of cell transplantation

XI Haitao1,2 , CHEN Lin1,3 , HUANG Hongyun 1,3 *, ZHANG Feng1,2 , LIU Yancheng 1,3, CHEN Di 1

1Beijing Hongtianji Neuroscience Academy, Beijing 100143

2Neurological Center,,Jingdong Zhongmei Hospital, Hebei Province  101601

3Center of Neurorestoratology, Beijing Rehabilitation Center, Beijing 100144

*Corresponding author: E-mail:hongyunh@gmail.com

ObjectiveTo investigate the long-term effects for patients with the sequeal of stroke  through multiple kinds of cell transplantation.

MethodsTen patients with sequeal of stroke were treated by multiple kinds of cell transplantation from November 2003 to April 2011. Among them, there were 6 males and 4 females and 6 cases with cerebral infarction, 4 cases with brain hemorrhage. Age from 42 to 87 years, average of 55.00±14.38 year old. The course of disease was ranged from 0.5 to 20 years, average of 5.80±5.71 years. According to Second Generation of Neurorestorotherapy, umbilical cord stromal cells, Schwann cells, neural progenitor cells, olfactory ensheathing cells were given through intravenous, intrathecal, parenchyma transplantation. The neurological function was assessed by clinic neurologic impairment scale and and Barthel Index before treatment and 0.5 to 2 year ( 1.45±0.60 years) follow-up. 

ResultTen patients achieved neurological function amelioration to different degrees during follow-up, which including speech, muscle strength,muscular tension, balance, pain and breathing. Barthel Index score increased from preoperative 59.50±28.52 points to postoperative 64.00±29.70 points (p=0.041). Clinic neurologic impairment scale score decreased from preoperative 13.60±8.44 points to postoperative 12.30±8.55 points (P=0.039).

ConclusionMultiple kinds of cell therapy for patients with sequeal of stroke is safe and feasible, which can improve their neurological functions and quality of life in some degree. 

Key wordsSequeal of stroke; Multiple kinds of cells; Transplantation; Second Generation of Neurorestorotherapy

 

 

 

多种细胞移植治疗脑卒中后遗症远期随访结果

郗海涛12 陈琳13 黄红云13 * 张峰12  刘彦铖13  陈娣1

作者单位:1北京市虹天济神经科学研究院(北京,100143

2京东中美医院神经中心(河北三河,101601

3北京康复中心神经修复中心(北京,100144

目的:观察多种细胞移植治疗脑卒中后遗症的远期疗效。

方法:随访102003-11/2011-4多种细胞移植治疗的脑卒中后遗症患者,其中男6例,女4例,年龄42-87岁,平均55.00±14.38岁。病程0.5-20年,平均病程5.80±5.71年。缺血性卒中6例,出血性卒中4例。采用神经修复第二代治疗方案,脐带间充质细胞、雪旺细胞、神经祖细胞、嗅鞘细胞分别经静脉,鞘内注射或脑内移植治疗。治疗前和0.5-2年(平均1.45±0.60)随访采用临床神经功能缺损评分及Barthel 指数评价。

结果:随访结果显示10例病人均有不同程度语言、肌力、肌张力、平衡、疼痛、呼吸等神经功能改善。Barthe 评分由59.50±28.52 增加到64.00±29.70p=0.041),临床神经功能评分由13.60±8.44降至12.30±8.55p=0.039)。术后和随访未发现长期发热、头痛、头晕、恶心及呕吐等并发症。

结论:多细胞移植治疗脑卒中安全可行,能在一定程度上改善患者神经功能和生存质量。

关键词:脑卒中后遗症 多种细胞 移植 神经修复第二代治疗

 

 

 

Description: 林欣荣

Shinn-Zong(John) Lin (Taiwan,China)

President of Beigang Hospital of China Medical UniversityProfessor of Neurosurgery of China Medical University

 

Intracerebral implantation of Stem Cells Promotes the Regeneration of Corticospinal Tracts in Stroke Patients

Shinn-Zong Lin1,2, 3, Demeral Liu1, Woei-Cherng Shyu1, 3

1Neuropsychiatry Center, China Medical University Hospital, Taichung, Taiwan

2Department of Neurosurgery, China Medical University Beigan Hospital, Yunlin, Taiwan

3 Graduate Institute of Immunology, China Medical University, Taichung, Taiwan

IntroductionOur animal study in chronic stroke rats showed that intracranial implantation of peripheral blood stem cells (PBSC) mobilized by granulocyte colony stimulating factor (GCSF) improved the anatomical regeneration of corticospinal tracts and motor function. Previous phase I trial in 6 old stroke patients by using antologous PBSC also revealed an improvement in functional outcome.

MethodsThis randomized, controlled phase II trials was conducted in 30 chronic stroke patients who suffered from stroke for 6 months up to 5 years with a stable neurological deficit. CD34+ PBSC about 3-8×106 were implanted stereotactically into the damaged corticosipnal tract under local anesthesia in the treatment group. The primary end points were improvement in NIHSS, European Stroke Scare (ESS), ESS motor subscale (EMS) and Modified Rankin Scale (mRS). The secondary end points were fiber numbers asymmetry (FNA) in corticospinal tract (CST) and motor evoked potential (MEP).

ResultsThere were no serious adverse events found in all 30 patients in the 12 months follow-up period. Significant improvements (p<0.05) were noted in NISS, ESS, EMS and mRS in treatment group as compared to control. FNAs were increased in every treated patient, but not in the control ones. MEP response reappeared in 9 of the 15 treated patients, but none in the control group.

ConclusionAutologous PBSC intracranial implantation in chronic stroke patients is safe and feasible.

 

 

 

Description: Barry Hoffer缩小

Barry J. Hoffer (USA)

Adjunct Professor, Case Western Reserve University, Neurosurgery and Genetics

 

 

 

Neuroprotective and Neuroregenerative Trophic Molecules in Parkinson ’s disease

Barry J. Hoffer

Although initially thought to be important primarily in neural development, a number of trophic proteins have been found to possess neuroprotective and neuroregenerative activity in the adult central system, particularly for midbrain dopamine neurons (MDN).  There is a considerable recent literature on trophic properties of TGF-ß superfamily proteins for MDN’s, including glial cell-derived neurotrophic factor (GDNF), neurturin, and bone morphogenetic proteins (BMPs).  This talk will review studies with the factors listed above, as well as describe more recent studies with two newly described trophic proteins, MANF and CDNF.  Data will be presented from various animal models of PD, both toxin and genetic, suggesting that these trophic proteins may eventually lead to novel PD therapeutics in man.  In addition, some data on small molecules with neuroprotective properties (AP4A, retinoic acid and vitamin D3) will also be presented.  The following table summarizes similarities and differences between neurotrophic factors GDNF, NRTN, CDNF and MANF from a potential clinical perspective.