Abstract:
Cell-based therapies hold great promise for brain repair after stroke. While accumulating evidence confirms the preclinical and clinical benefits of cell therapies, the underlying mechanisms by which they promote brain repair remain unclear. Here, we briefly review endogenous mechanisms of brain repair after ischemic stroke and then focus on how different stem and progenitor cell sources can promote brain repair. Specifically, we examine how transplanted cell grafts contribute to improved functional recovery either through direct cell replacement or by stimulating endogenous repair pathways. Additionally, we discuss recently implemented preclinical refinement methods, such as preconditioning, microcarriers, genetic safety switches, and universal (immune evasive) cell transplants, as well as the therapeutic potential of these pharmacologic and genetic manipulations to further enhance the efficacy and safety of cell therapies. By gaining a deeper understanding of post-ischemic repair mechanisms, prospective clinical trials may be further refined to advance post-stroke cell therapy to the clinic.
摘要:
基于细胞的疗法对中风后的大脑修复大有希望。虽然越来越多的证据证实了细胞疗法的临床前和临床益处,它们促进大脑修复的潜在机制仍不清楚。这里,我们简要回顾了缺血性卒中后脑修复的内源性机制,然后重点介绍了不同干细胞和祖细胞来源如何促进脑修复。具体来说,我们研究了移植的细胞移植物如何通过直接细胞置换或刺激内源性修复途径促进功能恢复.此外,我们讨论了最近实施的临床前改进方法,如预处理,微载体,遗传安全开关,和普遍(免疫规避)细胞移植,以及这些药物和基因操作的治疗潜力,以进一步提高细胞疗法的疗效和安全性。通过对缺血后修复机制的深入了解,前瞻性临床试验可能会进一步完善,以将卒中后细胞治疗推向临床.