Florey Institute for Neuroscience and Mental Health, University of Melbourne, Royal Parade, Parkville, Victoria 3010, Australia.
Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, S-22184 Lund, Sweden.
Neurobiol Dis. 2015 Jul;79:28-40. doi: 10.1016/j.nbd.2015.04.003. Epub 2015 Apr 22.
Pluripotent stem cells (embryonic stem cells, ESCs, and induced pluripotent stem cells, iPSCs) have the capacity to generate neural progenitors that are intrinsically patterned to undergo differentiation into specific neuronal subtypes and express in vivo properties that match the ones formed during normal embryonic development. Remarkable progress has been made in this field during recent years thanks to the development of more refined protocols for the generation of transplantable neuronal progenitors from pluripotent stem cells, and the access to new tools for tracing of neuronal connectivity and assessment of integration and function of grafted neurons. Recent studies in brains of neonatal mice or rats, as well as in rodent models of brain or spinal cord damage, have shown that ESC- or iPSC-derived neural progenitors can be made to survive and differentiate after transplantation, and that they possess a remarkable capacity to extend axons over long distances and become functionally integrated into host neural circuitry. Here, we summarize these recent developments in the perspective of earlier studies using intracerebral and intraspinal transplants of primary neurons derived from fetal brain, with special focus on the ability of human ESC- and iPSC-derived progenitors to reconstruct damaged neural circuitry in cortex, hippocampus, the nigrostriatal system and the spinal cord, and we discuss the intrinsic and extrinsic factors that determine the growth properties of the grafted neurons and their capacity to establish target-specific long-distance axonal connections in the damaged host brain.
多能干细胞（胚胎干细胞、ESCs 和诱导多能干细胞、iPSCs）具有生成内在模式化的神经祖细胞的能力，使其能够分化为特定的神经元亚型，并表达体内特性，与正常胚胎发育过程中形成的特性相匹配。近年来，由于开发了更精细的方案来从多能干细胞生成可移植的神经祖细胞，以及获得了用于追踪神经元连接以及评估移植神经元的整合和功能的新工具，在该领域取得了显著进展。最近在新生小鼠或大鼠大脑中的研究，以及在大脑或脊髓损伤的啮齿动物模型中，已经表明 ESC 或 iPSC 衍生的神经祖细胞可以在移植后存活和分化，并且它们具有显著的能力可以在长距离上延伸轴突，并在功能上整合到宿主神经回路中。在这里，我们从使用源自胎儿大脑的原代神经元的脑内和脊髓内移植的早期研究的角度总结这些最新进展，特别关注人 ESC 和 iPSC 衍生祖细胞重建皮质、海马体、黑质纹状体系统和脊髓中受损神经回路的能力，我们讨论决定移植神经元生长特性及其在受损宿主大脑中建立特定靶标的长距离轴突连接的能力的内在和外在因素。
