Department of Physiology and Neuroscience, University of Southern California, Los Angeles, CA 90033, USA.
Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Brain. 2024 Oct 3;147(10):3286-3305. doi: 10.1093/brain/awae204.
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 ischaemic 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-ischaemic repair mechanisms, prospective clinical trials may be further refined to advance post-stroke cell therapy to the clinic.
细胞疗法为中风后的大脑修复带来了巨大的希望。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，但它们促进大脑修复的潜在机制仍不清楚。在这里，我们简要回顾了缺血性中风后大脑修复的内源性机制，然后重点讨论了不同的干细胞和祖细胞来源如何促进大脑修复。具体来说，我们研究了移植细胞移植物如何通过直接细胞替代或通过刺激内源性修复途径来促进功能恢复。此外，我们还讨论了最近实施的临床前改进方法，如预处理、微载体、遗传安全开关和通用（免疫逃避）细胞移植，以及这些药理和遗传操作的治疗潜力，以进一步提高细胞疗法的疗效和安全性。通过更深入地了解缺血后修复机制，前瞻性临床试验可能会进一步改进，将中风后的细胞疗法推进到临床实践中。
