中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (1): 212-223.doi: 10.4103/NRR.NRR-D-24-00879

• 综述:脑损伤修复保护与再生 • 上一篇    下一篇

缺血性脑卒中后神经发生的增强：探索内源性和外源性干细胞之间的相互作用

  

  • 出版日期:2026-01-15 发布日期:2025-04-21
  • 基金资助:
    本研究得到了国家重点研发计划（编号：2018YFA0108602）、CAMS创新医学行动（编号：2021-1-I2M-019）、国家高水平医院临床研究基金（编号：2022-PUMCH-C-042）的资助。

Enhanced neurogenesis after ischemic stroke: The interplay between endogenous and exogenous stem cells

Ruxu Geng1 , Yuhe Wang1 , Renzhi Wang1 , Jun Wu2, *, Xinjie Bao1, 3, *   

  1. 1 Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China;  2 Stanford Cancer Institute, Stanford University, Stanford, CA, USA;  3 State Key Laboratory of Common Mechanism Research for Major Diseases, Beijing, China
  • Online:2026-01-15 Published:2025-04-21
  • Contact: Xinjie Bao, MD, baoxinjie1@pumch.cn; Jun Wu, PhD, jwu21@stanford.edu.
  • Supported by:
    This work was supported by the National Key Research and Development Program of China, No. 2018YFA0108602; the CAMS Initiative for Innovative Medicine, No. 2021-1-I2M-019; National High-Level Hospital Clinical Research Funding, No. 2022-PUMCH-C-042 (all to XB).

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摘要：

缺血性脑卒中是一个突出的全球健康危机，经常导致残疾或死亡，但可用的治疗干预措施却很少。尽管缺血性脑内启动了固有的修复过程，但这些过程常是不充分的，这促使人们研究植入外源干细胞作为一种潜在的治疗方式。这篇综述描述了缺血事件后成人大脑中内源性神经干细胞的本体和激活机制，特别强调了干细胞疗法对这些神经干细胞的影响。外源性干细胞已被证明可通过分泌生长因子、外泌体和细胞间接触直接增强内源性神经干细胞的增殖，并通过建立生物桥将干细胞从龛位招募到梗死区域。此外，这些细胞还能通过免疫调节和血管生成作用改变微环境，从而保障内源性神经再生。鉴于外源性干细胞和内源性干细胞之间的调控途径趋于一致，且需要一个有利的微环境，文章讨论了同时增强内源性和外源性干细胞疗效的3种策略：第一：在干细胞移植的同时，联合使用各种生长因子和药剂，以减轻干细胞凋亡；第二：协同注射外泌体和干细胞，以增强旁分泌效应；第三：将干细胞与水凝胶结合，为外源细胞提供保护性支架，同时促进内源性神经组织的再生和神经回路的重建。总之，关注内源性神经干细胞与外源性植入干细胞之间的相互作用和共同调控机制，可为提高干细胞疗法治疗缺血性脑卒中的疗效提供新的见解。

https://orcid.org/0000-0003-2117-7692 (Xinjie Bao); https://orcid.org/0000-0002-6701-2474 (Jun Wu)

关键词: BDNF, 内源性脑再生, 外泌体, 水凝胶, 缺血性脑卒中, 间充质干细胞, 神经干细胞, 神经发生, 再生, 干细胞移植

Abstract: Ischemic stroke is a significant global health crisis, frequently resulting in disability or death, with limited therapeutic interventions available. Although various intrinsic reparative processes are initiated within the ischemic brain, these mechanisms are often insufficient to restore neuronal functionality. This has led to intensive investigation into the use of exogenous stem cells as a potential therapeutic option. This comprehensive review outlines the ontogeny and mechanisms of activation of endogenous neural stem cells within the adult brain following ischemic events, with focus on the impact of stem cell-based therapies on neural stem cells. Exogenous stem cells have been shown to enhance the proliferation of endogenous neural stem cells via direct cell-tocell contact and through the secretion of growth factors and exosomes. Additionally, implanted stem cells may recruit host stem cells from their niches to the infarct area by establishing so-called “biobridges.” Furthermore, xenogeneic and allogeneic stem cells can modify the microenvironment of the infarcted brain tissue through immunomodulatory and angiogenic effects, thereby supporting endogenous neuroregeneration. Given the convergence of regulatory pathways between exogenous and endogenous stem cells and the necessity for a supportive microenvironment, we discuss three strategies to simultaneously enhance the therapeutic efficacy of both cell types. These approaches include: (1) co-administration of various growth factors and pharmacological agents alongside stem cell transplantation to reduce stem cell apoptosis; (2) synergistic administration of stem cells and their exosomes to amplify paracrine effects; and (3) integration of stem cells within hydrogels, which provide a protective scaffold for the implanted cells while facilitating the regeneration of neural tissue and the reconstitution of neural circuits. This comprehensive review highlights the interactions and shared regulatory mechanisms between endogenous neural stem cells and exogenously implanted stem cells and may offer new insights for improving the efficacy of stem cell-based therapies in the treatment of ischemic stroke.

Key words: brain-derived , neurotrophic , factor, endogenous neuroregeneration, exosomes, hydrogels, ischemic stroke, mesenchymal stem cells, neural stem cells, neurogenesis, stem cell transplantation