Chinese Journal of Tissue Engineering Research
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Ren Chao1 , Geng De-qin2 , Ge Wei2 , Li Jin-mei2
Online:
2013-06-04
Published:
2013-06-04
Contact:
Geng De-qin, M.D., Professor, Chief physician, Department of Neurology, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China
About author:
Ren Chao★, Studying for master’s degree, Teaching and Research Section of Neurology, Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China
CLC Number:
Ren Chao, Geng De-qin, Ge Wei, Li Jin-mei. Alternative treatment with stem cells for treatment of nervous system diseases: Hope or hype?[J]. Chinese Journal of Tissue Engineering Research, doi: 10.3969/j.issn.2095-4344.2013.23.018.
国内外干细胞治疗神经系统疾病的现状:探讨依据:从人民日报的2篇报道(见《 人民日报 》2012-05-07的09版及2012-05-27的08版),不难看出人们的问题集中在:干细胞治疗真有这么灵吗?有没有风险?干细胞治疗行业的乱象应如何规范?对于以上疑问,作者希望广大读者能在检索汇总的国内外一些相关研究文献中得到答案。 作者者通过万方数据库和PubMed全文数据库以“干细胞”、“动物模型”、“神经”等检索词变换组合检索相关资料,获得文献阅读后进一步剔除,最终结果显示:国内外已经完成阿尔茨海默病(Alzheimer's disease,AD)、脊髓损伤(spinal cord injury,SCI)、脑出血(cerebral hemorrhage,CH)、脑梗死(cerebral infarction,CI)、多发性硬化症(multiple sclerosis,MS)、肌萎缩侧索硬化症(amyotrophic lateral sclerosis,ALS)、帕金森病(Parkinsen' s disease,PD)、重症肌无力(myasthenia gravis,MG)、脑瘫(cerebral palsy,CP)、缺氧缺血性脑损伤(hypoxic-草药ischemic brain damage,HIBD)、血管性痴呆(vascular dementia,VD)、脑胶质瘤(glioma)、小脑萎缩(cerebellar atrophy,CA)、急性播散性脑脊髓炎(acute disseminated encephalomyelitis,ADEM)、颞叶癫痫(temporal lobe epilepsy,TLP)、创伤性脑损伤(traumatic brain injury,TBI)、假肥大型肌营养不良症(duchenne muscular dystrophy,DMD)、一氧化碳中毒致迟发性神经精神后遗症(delayed neuropsychiatric sequelae,DNPS)、脊髓性肌萎缩症(spinal muscular atrophy,SMA)、蛛网膜下腔出血(subarachnoid hemorrhage,SAH)、肝豆状核变性(hepatolenticular degeneration,HLD)、Tourette综合征即抽动秽语综合征(tourette syndrome,TS)、视网膜退行性病变(retinal degenerative diseases,RDD)、溶酶体贮积病(lysosomal storage diseases,LSDs)等疾病的动物模型的神经干细胞治疗研究[10-33] ,初步结果显示:在动物实验方面,神经干细胞对于神经系统损伤及退行性变有一定治疗作用。这其中值得关注的是日本京都大学高桥淳副教授领导的研究小组近期在《干细胞》上发表的用人胚胎干细胞成功使患帕金森症的猴子症状改善[34] ,这种新方法在3年后将有望用于临床治疗。 同时,通过万方数据库和PubMed全文数据库以“干细胞”、“临床研究”、“临床应用”、“神经”等检索词变换组合检索相关资料,获得文献阅读后进一步剔除,最终结果显示:在干细胞临床应用研究方面,受到很多限制[35] ,如在美国国立卫生研究院正式登记注册的干细胞临床试验已达3 985项(见表1:近几年较大的几项[36]),治疗涉及的疾病达100多种。其中,只有2种干细胞新药获批准。这期间美国前总统乔治•W•布什2001年颁布禁令,禁止联邦政府资助人类胚胎干细胞研究,但奥巴马上任后解除这一禁令,奥巴马政策的受益者较为著名的是总部设于美国马萨诸塞州的先进细胞技术公司,该公司于2010年11月在美国获得批准,可利用人类胚胎干细胞展开治疗斯格特病变(即青少年遗传性黄斑退化病变)的临床试验,2011年9月又获得英国药品与保健品管理局和基因治疗顾问委员会批准,可利用人类胚胎干细胞就青少年失明展开临床试验,成为欧洲范围内首次批准人类胚胎干细胞临床试验(http://www.ucl. ac.uk/ioo/research/patients White/news.htm)。面对阻力,临床应用方面的研究却依旧是惊喜不断,国内外大小规模的研究报道源源更新,一些国家已经从国家层面展开具有一定规模的临床试验,大多已进入临床Ⅱ[37-38] 、Ⅲ期[39] ,其中进展较快是美国Osiris医药公司的代表产品Prochymal[40] ,且于2012-05-17加拿大卫生监管机构已批准使用该公司的Prochymal药物治疗儿童急性移植抗宿主疾病,Prochymal成为全球首个获准用于治疗全身性疾病的干细胞药物。同时,各项干细胞相关专利传亦是捷报频传(见表2,仅举20世纪90年代部分为例[41] )。 中国干细胞研究虽然起步较晚,但在政府大力投入和科研人员不断突破创新之下,已处于继欧美发达国家之后第二梯队中的领先地位,特别是试验性干细胞临床应用研究更是处于世界先进水平。2006年,国务院将干细胞生物技术列入《国家中长期科学和技术发展规划纲要(2006/2020)》,作为纲要中需重点发展的8个技术领域的27项前沿技术之一。同时干细胞技术研究也被列入国家863和973计划,众多研究院所和医疗机构积极参与干细胞的基础研究和临床应用。陈国军等[42]应用计算机检索2004至2010年中国期刊全文数据库(维普医药信息资源系统),检索“干细胞与脑”相关中文文献共检索到352篇,对其中有价值的20篇进行了分析,结果:①365例年龄为2-86岁,治疗的脑疾病有脑瘫、脑出血、脑梗死、脑萎缩等,其中脑瘫最多(356%),见图2。②移植细胞以自体骨髓间充质干细胞和异体胚转化神经干细胞比例高(732%)。③移植途径以腰椎管移植途径最高(499%)。④治疗效果良好,不良反应少,6个月随访显示效果持续存在,并得出“干细胞疗法可以治疗多种脑疾病,适用年龄范围大,自体骨髓间充质干细胞腰椎管移植途径可行性高,治疗有效,但干细胞疗法的效果需要更多的临床病例和随访资料证实。”的结论。目前,国内没有制定统一的和(或)优先的干细胞培养、鉴定方法及干细胞移植途径、移植条件及移植时间窗的规范和(或)指南[43] ,导致出现一些负面报道,但国家已经开始从2009年起开始着手逐步规整(http://www.stemcellsportal.com)。"
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