I-Stem, INSERM UMR861, UEVE, Evry Cedex, France.
Cell Transplant. 2012;21(12):2587-602. doi: 10.3727/096368912X653228. Epub 2012 Aug 10.
Human induced pluripotent stem cells (hiPSCs) are a most appealing source for cell replacement therapy in acute brain lesions. We evaluated the potential of hiPSC therapy in stroke by transplanting hiPSC-derived neural progenitor cells (NPCs) into the postischemic striatum. Grafts received host tyrosine hydroxylase-positive afferents and contained developing interneurons and homotopic GABAergic medium spiny neurons that, with time, sent axons to the host substantia nigra. Grafting reversed stroke-induced somatosensory and motor deficits. Grafting also protected the host substantia nigra from the atrophy that follows disruption of reciprocal striatonigral connections. Graft innervation by tyrosine hydoxylase fibers, substantia nigra protection, and somatosensory functional recovery were early events, temporally dissociated from the slow maturation of GABAergic neurons in the grafts and innervation of substantia nigra. This suggests that grafted hiPSC-NPCs initially exert trophic effects on host brain structures, which precede integration and potential pathway reconstruction. We believe that transplantation of NPCs derived from hiPSCs can provide useful interventions to limit the functional consequences of stroke through both neuroprotective effects and reconstruction of impaired pathways.
人类诱导多能干细胞（hiPSCs）是急性脑损伤细胞替代治疗最有吸引力的来源。我们通过将 hiPSC 衍生的神经祖细胞（NPCs）移植到缺血后纹状体中来评估 hiPSC 治疗中风的潜力。移植物接收宿主酪氨酸羟化酶阳性传入纤维，并包含发育中的中间神经元和同源 GABA 能中等棘突神经元，随着时间的推移，这些神经元的轴突投射到宿主黑质。移植逆转了中风引起的感觉和运动缺陷。移植还保护宿主黑质免受纹状体-黑质回路中断后引起的萎缩。酪氨酸羟化酶纤维的移植神经支配、黑质保护和感觉功能恢复是早期事件，与移植物中 GABA 能神经元的缓慢成熟和黑质的神经支配在时间上分离。这表明，移植的 hiPSC-NPCs 最初对宿主脑结构发挥营养作用，这先于整合和潜在的通路重建。我们认为，源自 hiPSCs 的 NPC 移植可以通过神经保护作用和受损通路的重建，为限制中风的功能后果提供有用的干预措施。
