细胞移植神经修复临床应用原则(征求意见稿)

1、细胞移植神经修复临床应用原则（征求意见稿）国际神经修复学会细胞移植作为神经修复学研究的重要内容，部分国家已经成功应用于临床。为使细胞移植在神经修复领域研究应用更加规范，符合国际公认准则，遵守相关规定，结合转化医学理念，促进该方面研究健康、快速发展，进一步确保临床安全性和提高有效程度，本学会提出如下应用原则：第一条 来源于人胚胎的各类细胞须严格按照所在国的法律、法规开展临床科研和治疗工作，并且需要孕妇签署捐献知情同意书。第二条 来源于人体的各类体细胞须严格按照所在国的法律、法规开展临床科研和治疗工作。第三条 细胞移植临床应用前，灵长类动物模型实验并非必备条件。对急性和亚急性致命性疾病，应争取时间

2、积极探索各种临床干预手段，尽量延长患者生命。第四条 在治疗病人期间，当证明不存在预防和治疗方法，或者这些方法不起任何作用，医生如果根据自己的判断，认为有挽救病人生命的希望，和恢复他们的健康或减轻他们的痛苦，在征得病人知情同意后，完全可以运用未被完全论证的新的预防和治疗措施。第五条 I期临床试验病例数建议为510例，II期试验病例数为2040例，III期试验病例数为120200例。试验设计应经所在单位伦理委员会严格审查并获得同意。如发现风险超过潜在利益，应该中止其研究；如有确切证据表明只有正面利益，即可中止其研究，直接用于临床常规治疗。第六条 目前临床研究证实有效或具有应用前景的细胞种类包括胚胎

3、脑细胞（如中脑黑质细胞）、嗅鞘细胞、神经干细胞、神经祖/前体细胞、骨髓基质细胞、施万细胞、脐血单核细胞、胚胎干细胞、视网膜色素上皮细胞、胚胎脊髓细胞、羊膜细胞等。对细胞的安全性、有效性和作用机理，应加大基础和临床研究力度。第七条 目前临床治疗和研究疾病种类主要包括帕金森病、脊髓损伤、肌萎缩侧索硬化、脑卒中、脑性瘫痪、颅脑损伤、共济失调、多发性硬化、痴呆、持续性植物生存状态、脊髓炎后遗症、脊肌萎缩症等。部分疾病近期疗效肯定，研究重点应探讨中长期治疗效果。第八条 目前使用途径包括脑内（脑实质或脑室）和脊髓内移植、鞘内植入以及静脉或动脉输注等。不同疾病和不同移植细胞种类，理论上存在最适宜应用方式，应

4、在动物试验基础上，逐步建立规范细胞植入途径和最佳细胞用量。第九条 虽然动物实验结果似乎支持使用免疫抑制剂，但临床上，中枢神经系统细胞移植后是否需用免疫抑制剂，目前尚存在争论，建议作为今后一项重要研究课题。第十条 所有医案和新的信息应该被记录下来，适当时候可以发表。对于细胞移植神经修复的各类对照研究结果，应该及时分析总结，分阶段公开发表，以供其他研究者参考、对比和进一步验证。第十一条 不断加强转化医学意识，当证明两种细胞均有一定临床疗效时，鼓励尽早适时进行联合移植研究，以不断探索新策略，提高治疗有效程度；鼓励适时地联合使用药物、物理、化学、生物、生物工程等多种手段，提高治疗效果。第十二条 积极推

5、动神经修复领域前瞻性多中心国际合作细胞移植研究。参考文献1. 赫尔辛基宣言（2000）The neural restorative cell transplantation clinical practice principle (Seeking suggestions)International Association of Neural RestorationAs cell transplantation is a valuable theme of neural restoration research, several countries have already succeeded

6、using it for clinical practices. In order to bring the therapeutic strategy of cell transplant to a higher neural repair research application standard while conform to the internationally recognized criterion, follow the relevant policies, combine translational medicine idea, and also promote the he

7、althy and fast development of neural restoration research, thus further safeguard the clinical safety and make it more effective, the association proposes the following application principles: 1. Any researches involve human fetal cells must follow host country's laws and regulations while condu

8、cting clinical scientific research and providing treatment. The pregnant woman need to know the exact circumstances and written permission must be obtained.2. Any researches involve cells from human body must follow host country's laws and regulations while conducting clinical scientific researc

9、h and providing treatment.3. Prior to cell transplant clinical practice, primate animal models experiment is not an absolute requirement. For acute and subacute life threatening disease, the physician should act quickly to explore clinical intervention methods, in order to prolong patients' surv

10、ival duration as far as possible.4. In the treatment of a patient, where proven prophylactic, diagnostic and therapeutic methods do not exist or have been ineffective, the physician, with informed consent from the patient or his/her family, must be free to use unproven or new prophylactic, diagnosti

11、c and therapeutic measures, if in the physician's judgments it offers hope of saving life, re-establishing health or alleviating suffering. 5. Phase I clinical trials should include 5-10 patients, Phase II clinical trials should include 20-40 patients, Phase III clinical trials should include 12

12、0-200 patients. The experimental design should pass through rigorous examination and obtain permission from ethics committee. The physician should cease any investigation if the risks are found to outweigh the potential benefits. If there is conclusive proof of positive and beneficial results, the c

13、linical trial can be stopped and it can be used as a conventional clinical treatment method.6. Currently, the clinical research has confirmed the following cells are effective or have clinical application prospect. The cell types include the embryo brain cell (for example mesencephalic nigral cells)

14、, olfactory ensheathing cell, the neural stem cell, the neural progenitor/precursor cell, the bone marrow stromal cells, Schwann cells, umbilical cord blood mononuclear cell, the embryo stem cell, the retinal pigment epithelial cells, the embryo spinal cord cell, the amnion cell and so on. The physi

15、cian should conduct thorougher research regarding cells' safety, validity, and the mechanism while enlarge the foundation and clinical research dynamics.7. Presently, the neurological diseases intervened by using cells therapy in clinic mainly involves Parkinson diseases, spinal cord injury, amy

16、otrophic lateral sclerosis, cerebral palsy, stroke, brain injury, dystaxia, multiple sclerosis, Huntington disease, dementia, persistent vegetative state, sequela of myelitis, spinal muscular atrophy and so on. For some of those diseases, the definite short term benefits have been found, the future

17、research should be emphasized on discussing the middle and long term treatment results.8. Currently, the cell injection methods include: intracerebral (cerebral parenchyma and ventricle), intra spinal cord, intrathecal as well as in the vein or in the artery and so on. As diseases are different and

18、types of transplanted cells are different, theoretically there is a most suitable way for each type of disease. However, the physician should base their research on animal experiments; while gradually establish the standard regarding the location of cell implant and the best amount of cells used.9.

19、Although the animal experiments result supports the use of immunosuppressant, but on the clinical application, the physicians are still debating whether it is necessary to use immunosuppressant after the central nervous system cell transplantation. It should be considered an important research topic

20、 in the future.10. All medical files and the recent information should be record, at a suitable time it could be published. Regarding the comparison findings of cell transplants' neural regeneration, the physicians should act promptly to analyze and summarize the results. The physicians should publish results by clinical phases for other researchers to refer, to compare, and further to confirm.11. Contin