干细胞衍生物：突破活细胞治疗局限的多靶点脑细胞保护生物制品

doi:10.3969/j.issn.1673-5765.2026.05.006

中国卒中杂志 ›› 2026, Vol. 21 ›› Issue (5): 561-569.DOI: 10.3969/j.issn.1673-5765.2026.05.006

干细胞衍生物：突破活细胞治疗局限的多靶点脑细胞保护生物制品

陈玮琪^1，2，江凌玲^1，2，何菂^1，2，陈彦博^2，3，张枘南¹，刘欣如¹，刘文竹¹，郭蕾¹，王玲¹，王伊龙^{1，2，4，5，6，7}

1北京 100070 首都医科大学附属北京天坛医院神经病学中心
2北京 100160 天坛-达尔文渐冻症及神经修复技术转化联合实验室
3武汉 430074 达尔文生物科技（湖北）有限公司
4北京 100070 国家神经疾病医学中心
5北京 100070 神经系统疾病国家临床医学研究中心
6北京 100069 首都医科大学人脑保护高精尖创新中心
7北京 102206 北京脑科学与类脑研究所

收稿日期:2026-01-11 修回日期:2026-04-16 接受日期:2026-05-10 出版日期:2026-05-20 发布日期:2026-05-20
通讯作者: 王伊龙 yilong528@aliyun.com

Stem Cell Derivatives: Multi-Target Brain Cytoprotective Biological Products Beyond the Limitations of Live Cell Therapy

CHEN Weiqi^1,2, JIANG Lingling^1,2, HE Di^1,2, CHEN Yanbo^2,3, ZHANG Ruinan¹, LIU Xinru¹, LIU Wenzhu¹, GUO Lei¹, WANG Ling¹, WANG Yilong^1,2,4,5,6,7

1Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
2ALS & Neuralregeneration Technologies Translation Joint Lab
3Beijing Darwin Cell Biotechnology Co., Ltd, Wuhan 430074, China
4National Center for Neurological Disorders, Beijing 100070, China
5China National Clinical Research Center for Neurological Diseases, Beijing 100070, China
6Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 100069, China
7Chinese Institute for Brain Research, Beijing 102206, China

Received:2026-01-11 Revised:2026-04-16 Accepted:2026-05-10 Online:2026-05-20 Published:2026-05-20
Contact: WANG Yilong, E-mail: yilong528@aliyun.com

摘要/Abstract

摘要： 对于神经系统疾病所致的神经功能缺损，传统单靶点脑细胞保护剂的临床疗效有限。干细胞治疗虽具备多靶点脑细胞保护潜力，但受限于其在体内存活率低、可导致脑内炎症反应及有致瘤风险等局限性，临床转化遭遇瓶颈。干细胞衍生物是去细胞化的生物制品，通过富集干细胞旁分泌活性成分（如干细胞分泌组和细胞外囊泡），在保留干细胞多效性脑细胞保护功能的同时，规避了活细胞治疗的安全性与异质性风险。本文系统综述了干细胞衍生物的作用机制及相关基础实验和临床研究现状。在作用机制层面，干细胞衍生物可通过调控炎症反应和免疫微环境、促进血管与神经再生及介导细胞间物质转运等机制，形成系统性神经修复、再生的脑细胞保护新范式。目前，干细胞衍生物已在肌萎缩侧索硬化、多系统萎缩及缺血性卒中等疾病的相关研究中初步展现了脑细胞保护作用潜力与良好的安全性。值得关注的是，在目前更严格的生物医学研究和转化管理规范背景下，作为更具标准化与产业化前景的“现货型”策略，干细胞衍生物有望突破当前脑细胞保护治疗的成药性困境，引领脑细胞保护领域进入非细胞生物制品治疗时代。

文章导读： 干细胞衍生物作为去细胞化的生物制品，保留了干细胞在神经系统疾病脑损伤中的多靶点脑细胞保护作用，且避免了干细胞体内存活率低、可导致脑内炎症反应及有致瘤风险等局限性，已经成为了具有临床转化价值的脑细胞保护剂。

关键词: 脑细胞保护; 干细胞衍生物; 非细胞生物制品; 旁分泌效应; 临床转化

Abstract: For neurological deficits caused by nervous system diseases, the clinical efficacy of conventional single-target brain cytoprotective agents is limited. Although stem cell therapy holds the potential for multi-target brain cytoprotection, its clinical translation is hindered by challenges such as a low in vivo survival rate, potential to induce intracerebral inflammation, and risks of tumorigenicity. Stem cell derivatives are acellular biological products that, by enriching the paracrine active components (including stem cell secretome and extracellular vesicles), retain the pleiotropic brain cytoprotective functions of stem cells while significantly circumventing the safety and heterogeneity risks associated with live cell therapy. This article systematically reviews the mechanisms of action of stem cell derivatives and the current status of related basic and clinical research. Regarding the mechanisms of action, these derivatives can modulate the inflammatory and immune microenvironment, promote angiogenesis and neuroregeneration, and mediate intercellular substance transport, thereby establishing a new paradigm for systemic neural repair and regeneration in brain cytoprotection. Currently, stem cell derivatives have shown preliminary brain cytoprotective potential and favorable safety in research on diseases such as amyotrophic lateral sclerosis, multiple system atrophy, and ischemic stroke. Notably, in the context of increasingly stringent biomedical research and translational regulatory frameworks, as an “off-the-shelf” strategy with greater potential for standardization and industrialization, stem cell derivatives are expected to overcome the current druggability limitations in brain cytoprotection therapy and usher the field into an era of noncellular biological products.

Key words: Brain cytoprotection; Stem cell derivative; Noncellular biological product; Paracrine effect; Clinical translation

中图分类号:

陈玮琪, 江凌玲, 何菂, 陈彦博, 张枘南, 刘欣如, 刘文竹, 郭蕾, 王玲, 王伊龙. 干细胞衍生物：突破活细胞治疗局限的多靶点脑细胞保护生物制品[J]. 中国卒中杂志, 2026, 21(5): 561-569.

CHEN Weiqi, JIANG Lingling, HE Di, CHEN Yanbo, ZHANG Ruinan, LIU Xinru, LIU Wenzhu, GUO Lei, WANG Ling, WANG Yilong. Stem Cell Derivatives: Multi-Target Brain Cytoprotective Biological Products Beyond the Limitations of Live Cell Therapy[J]. Chinese Journal of Stroke, 2026, 21(5): 561-569.

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链接本文: https://www.chinastroke.org.cn/CN/10.3969/j.issn.1673-5765.2026.05.006

https://www.chinastroke.org.cn/CN/Y2026/V21/I5/561

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干细胞衍生物：突破活细胞治疗局限的多靶点脑细胞保护生物制品

Stem Cell Derivatives: Multi-Target Brain Cytoprotective Biological Products Beyond the Limitations of Live Cell Therapy

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