Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, M5S 3E1, Canada.
Institute of Medical Science, University of Toronto, Toronto, Ontario, M5S 3E1, Canada.
Transl Stroke Res. 2020 Feb;11(1):93-107. doi: 10.1007/s12975-019-0691-x.
Stroke is one of the leading causes of long-term disability. Cell transplantation is a promising strategy to treat stroke. We explored the efficacy of directly reprogrammed human neural precursor cell (drNPC) transplants to promote functional recovery in a model of focal ischemic stroke in the mouse sensorimotor cortex. We show that drNPCs express neural precursor cell markers and are neurally committed at the time of transplantation. Mice that received drNPC transplants recovered motor function, irrespective of transplant vehicle or recipient sex, and with no correlation to lesion volume or glial scarring. The majority of drNPCs found in vivo, at the time of functional recovery, remained undifferentiated. Notably, no correlation between functional recovery and long-term xenograft survival was observed, indicating that drNPCs provide therapeutic benefits beyond their survival. Furthermore, increased synaptophysin expression in transplanted brains suggests that drNPCs promote neuroplasticity through enhanced synaptogenesis. Our findings provide insight into the mechanistic underpinnings of drNPC-mediated recovery for stroke and support the notion that drNPCs may have clinical applications for stroke therapy.
中风是长期残疾的主要原因之一。细胞移植是治疗中风的一种很有前途的策略。我们研究了直接重编程的人类神经前体细胞（drNPC）移植在小鼠感觉运动皮层局灶性缺血性中风模型中促进功能恢复的效果。我们发现 drNPC 表达神经前体细胞标志物，并在移植时具有神经定向性。接受 drNPC 移植的小鼠恢复了运动功能，与移植载体或受体性别无关，与病变体积或神经胶质瘢痕无关。在功能恢复时，体内发现的大多数 drNPC 仍然未分化。值得注意的是，功能恢复与长期异种移植物存活之间没有相关性，这表明 drNPC 提供了超越其存活的治疗益处。此外，移植脑内突触素表达增加表明 drNPC 通过增强突触发生促进神经可塑性。我们的发现为 drNPC 介导的中风恢复的机制基础提供了深入了解，并支持 drNPC 可能具有中风治疗的临床应用的观点。
