細(xì)胞移植神經(jīng)修復(fù)臨床應(yīng)用原則(征求意見稿)

1、細(xì)胞移植神經(jīng)修復(fù)臨床應(yīng)用原則（征求意見稿）國(guó)際神經(jīng)修復(fù)學(xué)會(huì)細(xì)胞移植作為神經(jīng)修復(fù)學(xué)研究的重要內(nèi)容，部分國(guó)家己經(jīng)成功應(yīng)用于臨床。 為使細(xì)胞移植在神經(jīng)修復(fù)領(lǐng)域研究應(yīng)用更加規(guī)范，符合國(guó)際公認(rèn)準(zhǔn)則，遵守相關(guān) 規(guī)定，結(jié)合轉(zhuǎn)化i矢學(xué)理念，促進(jìn)該方面研究健康、快速發(fā)展，進(jìn)一步確保臨床安 全性和提高有效程度，木學(xué)會(huì)提出如下應(yīng)用原則：第一條來源于人胚胎的各類細(xì)胞須嚴(yán)格按照所在國(guó)的法律、法規(guī)開展臨床 科研和治療工作，并且需要孕婦簽署捐獻(xiàn)知情同意書。第二條來源于人體的各類體細(xì)胞須嚴(yán)格按照所在國(guó)的法律、法規(guī)開展臨床 科研和治療工作。第三條細(xì)胞移植臨床應(yīng)用前，靈長(zhǎng)類動(dòng)物模型實(shí)驗(yàn)并非必備條件。對(duì)急性 和亞急性致命性疾病，應(yīng)

2、爭(zhēng)取時(shí)間積極探索各種臨床干預(yù)手段，盡量延長(zhǎng)患者牛 命。第四條 在治療病人期間，當(dāng)證明不存在預(yù)防和治療方法，或者這些方法不 起任何作用，醫(yī)牛如果根據(jù)自己的判斷，認(rèn)為有挽救病人生命的希望，和恢復(fù)他 們的健康或減輕他們的痛苦，在征得病人知情同意后，完全可以運(yùn)用未被完全論 證的新的預(yù)防和治療措施。第五條i期臨床試驗(yàn)病例數(shù)建議為510例，ii期試驗(yàn)病例數(shù)為2040例，iii 期試驗(yàn)病例數(shù)為120200例。試驗(yàn)設(shè)計(jì)應(yīng)經(jīng)所在單位倫理委員會(huì)嚴(yán)格審查并獲得 同意。如發(fā)現(xiàn)風(fēng)險(xiǎn)超過潛在利益，應(yīng)該中止其研究；如有確切證據(jù)表明只有正面 利益，即可中止其研究，直接用于臨床常規(guī)治療。第六條目前臨床研究證實(shí)有效或具有應(yīng)用前景

3、的細(xì)胞種類包括胚胎腦細(xì) 胞（如中腦黑質(zhì)細(xì)胞）、嗅鞘細(xì)胞、神經(jīng)干細(xì)胞、神經(jīng)祖/前體細(xì)胞、骨髓基質(zhì)細(xì) 胞、施萬細(xì)胞、臍血單核細(xì)胞、胚胎干細(xì)胞、視網(wǎng)膜色素上皮細(xì)胞、胚胎脊髓細(xì) 胞、羊膜細(xì)胞等。對(duì)細(xì)胞的安全性、有效性和作用機(jī)理，應(yīng)加大基礎(chǔ)和臨床研究 力度。第七條 目前臨床治療和研究疾病種類主要包括帕金森病、脊髓損傷、肌萎 縮側(cè)索硬化、腦卒中、腦性癱瘓、顱腦損傷、共濟(jì)失調(diào)、多發(fā)性硬化、癡呆、持 續(xù)性植物生存狀態(tài)、脊髓炎后遺癥、脊肌萎縮癥等。部分疾病近期療效肯定，研 究重點(diǎn)應(yīng)探討中長(zhǎng)期治療效果。第八條 目前使用途徑包扌舌腦內(nèi)（腦實(shí)質(zhì)或腦室）和脊髓內(nèi)移植、鞘內(nèi)植入 以及靜脈或動(dòng)脈輸注等。不同疾病和不同移植細(xì)

4、胞種類，理論上存在最適宜應(yīng)用 方式，應(yīng)在動(dòng)物試驗(yàn)基礎(chǔ)上，逐步建立規(guī)范細(xì)胞植入途徑和最佳細(xì)胞用量。第九條 雖然動(dòng)物實(shí)驗(yàn)結(jié)果似乎支持使用免疫抑制劑，但臨床上，中樞神經(jīng) 系統(tǒng)細(xì)胞移植后是否需用免疫抑制劑，目前尚存在爭(zhēng)論，建議作為今后一項(xiàng)重耍 研究課題。第十條所有醫(yī)案和新的信息應(yīng)該被記錄下來，適當(dāng)時(shí)候可以發(fā)表。對(duì)于細(xì) 胞移植神經(jīng)修復(fù)的各類對(duì)照研究結(jié)果，應(yīng)該及時(shí)分析總結(jié)，分階段公開發(fā)表，以 供其他研究者參考、對(duì)比和進(jìn)一步驗(yàn)證。第十一條不斷加強(qiáng)轉(zhuǎn)化醫(yī)學(xué)意識(shí)，當(dāng)證明兩種細(xì)胞均有一定臨床療效時(shí)， 鼓勵(lì)盡早適時(shí)進(jìn)行聯(lián)合移植研究，以不斷探索新策略，提高治療有效程度；鼓勵(lì) 適時(shí)地聯(lián)合使用藥物、物理、化學(xué)、生物、生物

5、工程等多種手段，提高治療效果。第十二條積極推動(dòng)神經(jīng)修復(fù)領(lǐng)域前瞻性多中心國(guó)際合作細(xì)胞移植研究。參考文獻(xiàn)1.赫爾辛基宣言(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 hav

6、e already succeeded using it for clinical practices in order to bring the therapeutic strategy of cell transplant to a higher neural repair research application stan dard while conform to the in ternatio nally recognized criterion, follow the releva nt policies, combine translational medicine idea,

7、and also promote the healthy 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 r

8、egulations while conducting 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 clini

9、cal scientific research 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 prolo

10、ng patients1 survival 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 prophy

11、lactic, diag no stic and therapeutic measures, if i n the physicia nfs judgme nts it offers hope of saving life, re-establishing health or alleviating suffering.5. phase i clinical trials should in elude 5-10 patients, phase ii clin ical trials should include 20-40 patients, phase iii clinical trial

12、s should include 120-200 patients. the experimental design should pass through rigorous exami nation and obtain permissi on from ethics committee the physician should cease any investigation if the risks are found to outweigh the potential benefits. if there is con elusive proof of positive and bene

13、ficial results, the clinical trial can be stopped and it can be used as a conventional clinical treatment method6. currently, the clinical research has confirmed the following cells are effective or have clinical application prospect. the cell types in elude the embryo brain cell (for example mesenc

14、ephalic nigral cells), olfactory ensheathing cell, the neural stem cell, the neural proge nitor/precursor cell, the bone marrow stromal cells, schwa rm cells, umbilical cord blood mononuclear cell, the embryo stem cell, the retinal pigment epithelial cells, the embryo spinal cord cell, the amnion ce

15、ll and so on. the physician should conduct thorougher research regarding cells1 safety, validity, and the mechanism while enlarge the foundation and clinical research dynamics7. presently, the neurological diseases intervened by using cells therapy in clinic mainly involves parkinson diseases, spina

16、l cord injury, amyotrophic 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

17、found5 the future research should be emphasized on discussing the middle and long term treatment results8. 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 a

18、re different and 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 o

19、f cells used9. 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 transplantatiori. itshould be considered an important

20、 research topic in the future10. 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 confirm11. continuou