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干细胞移植改善缺血性卒中后功能障碍的研究进展

  

  1. 210011 江苏省南京市,南京医科大学第二附属医院神经内科

Research progress on stem cell transplantation-based therapies for functional recovery after ischemic stroke

  1. Department of Neurology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China

摘要: 缺血性卒中引发的运动、感觉及高级神经功能障碍是导致患者长期残疾的主因,构建超越急性再灌注时间窗的神经修复策略已成为再生医学的核心议题。干细胞移植凭借其在损伤微环境调节、神经营养支持、血管新生及多谱系细胞替代等方面的巨大潜能,成为卒中后功能重建最具前景的研究方向之一。本文系统综述了单一型细胞移植、脑类器官移植及其分子与神经环路机制和临床转化的最新研究进展。现有证据表明:间充质干细胞主要通过旁分泌、免疫调控与促进血管新生效应优化修复微环境;神经干/祖细胞及多能干细胞衍生[1]神经元则在神经元替代、再髓鞘化及特定功能环路整合中展现出结构性修复优势;脑类器官移植则为大体积皮层缺损的组织级重建提供了创新路径。此外,针对 CXCL12-CXCR4、IGF-1/PI3K/AKT/YAP 及外泌体介导的移植物—宿主交互机制研究,正为精准再生干预提供坚实的理论实证。综上,干细胞疗法为卒中康复提供了关键的再生医学思路,但其细胞特异性应用场景、最优递送范式及远期临床有效性仍亟待标准化、高质量研究予以进一步确证。



作者单位:210011 江苏省南京市,南京医科大学第二附属医院神经内科

通信作者:吴晋, Email:wujin@njmu.edu.cn

关键词: 缺血性卒中, 干细胞移植, 类器官移植, 神经环路重建, 临床转化

Abstract: Persistent motor, sensory and higher neurological deficits after ischemic stroke are important causes of long-term disability in patients. Developing repair strategies beyond acute reperfusion therapy has become an important issue in neurorestoration research. Stem cell transplantation, which has the potential to regulate the post-injury microenvironment, provide neurotrophic support, promote vascular remodeling and to some extent replace cells, has become one of the important directions in the study of functional reconstruction after stroke. This article reviews the relevant research in recent years, focusing on single-cell transplantation, brain organoid transplantation, molecular and circuit mechanisms, and clinical translation progress. Existing evidence shows that mesenchymal stem cells mainly improve the repair environment through paracrine, immunomodulatory and pro-angiogenic effects; neural stem/progenitor cells and pluripotent stem cell-derived neurons may have more direct structural repair advantages in neuronal replacement, remyelination and specific circuit integration; brain organoid transplantation provides new experimental evidence for tissue-level reconstruction of large cortical defects. At the same time, studies on CXCL12-CXCR4, IGF-1-PI3K/AKT-Hippo/YAP, exosome-mediated signaling and graft-host molecular interactions are providing experimental evidence for mechanism-oriented regenerative intervention. Stem cell transplantation provides important regenerative medicine ideas for functional recovery after ischemic stroke, but the applicable scenarios of different cell types, the best delivery strategies, long-term safety and clinical effectiveness still need to be further clarified by high-quality, standardized research.

Key words: ischemic stroke, stem cell transplantation, organoid transplantation, neural circuit reconstruction, clinical translation