Laboratory of Neural Stem Cell Biology and Therapy, University Hospital, Lund, Sweden.
Stem Cells. 2012 Jun;30(6):1120-33. doi: 10.1002/stem.1104.
Reprogramming of adult human somatic cells to induced pluripotent stem cells (iPSCs) is a novel approach to produce patient-specific cells for autologous transplantation. Whether such cells survive long-term, differentiate to functional neurons, and induce recovery in the stroke-injured brain are unclear. We have transplanted long-term self-renewing neuroepithelial-like stem cells, generated from adult human fibroblast-derived iPSCs, into the stroke-damaged mouse and rat striatum or cortex. Recovery of forepaw movements was observed already at 1 week after transplantation. Improvement was most likely not due to neuronal replacement but was associated with increased vascular endothelial growth factor levels, probably enhancing endogenous plasticity. Transplanted cells stopped proliferating, could survive without forming tumors for at least 4 months, and differentiated to morphologically mature neurons of different subtypes. Neurons in intrastriatal grafts sent axonal projections to the globus pallidus. Grafted cells exhibited electrophysiological properties of mature neurons and received synaptic input from host neurons. Our study provides the first evidence that transplantation of human iPSC-derived cells is a safe and efficient approach to promote recovery after stroke and can be used to supply the injured brain with new neurons for replacement.
重编程成体人类体细胞为诱导多能干细胞（iPSCs）是一种产生用于自体移植的患者特异性细胞的新方法。这些细胞是否能长期存活、分化为功能性神经元，并在中风损伤的大脑中诱导恢复尚不清楚。我们已经将从成体人纤维母细胞衍生的 iPSC 生成的长期自我更新的神经上皮样干细胞移植到中风损伤的小鼠和大鼠纹状体或皮质中。移植后 1 周即可观察到手部运动的恢复。改善可能不是由于神经元替代引起的，而是与血管内皮生长因子水平的增加有关，可能增强了内源性可塑性。移植细胞停止增殖，在不形成肿瘤的情况下至少可以存活 4 个月，分化为不同亚型的形态成熟神经元。纹状体内移植物的神经元发出轴突投射到苍白球。移植的细胞表现出成熟神经元的电生理特性，并从宿主神经元接收突触输入。我们的研究首次提供了证据，证明人 iPSC 衍生细胞的移植是一种安全有效的促进中风后恢复的方法，可用于向损伤的大脑提供新的神经元以替代。
