Long-distance growth and connectivity of neural stem cells after severe spinal cord injury.
Long-distance growth and connectivity of neural stem cells after severe spinal cord injury.
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DOI：
10.1016/j.cell.2012.08.020
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发表时间：
2012-09-14
期刊：
影响因子：
64.5
通讯作者：
Tuszynski MH
中科院分区：
文献类型：
--
作者：
Lu P;Wang Y;Graham L;McHale K;Gao M;Wu D;Brock J;Blesch A;Rosenzweig ES;Havton LA;Zheng B;Conner JM;Marsala M;Tuszynski MH
将表达GFP的神经干细胞（NSC）嵌入含有生长因子混合物的纤维蛋白基质中，并移植到严重脊髓损伤的部位。移植的细胞分化成多种细胞表型，包括神经元，其将大量轴突延伸到显著的距离。延伸的轴突与宿主细胞形成丰富的突触。轴突生长部分依赖于哺乳动物雷帕霉素靶蛋白（mTOR），但不依赖于Nogo信号。移植的神经元支持形成电生理继电器的网站完全脊髓横断，导致功能恢复。两个人干细胞系（566RSC和HUES7）包埋在含生长因子的纤维蛋白表现出相似的生长，和566RSC细胞支持功能恢复。因此，早期阶段神经元固有的特性可以克服损伤的成年脊髓的抑制环境，以引起显著的轴突生长，从而形成显著改善功能的新型中继电路。这些治疗特性跨越干细胞来源和物种。
Neural stem cells (NSCs) expressing GFP were embedded into fibrin matrices containing growth factor cocktails and grafted to sites of severe spinal cord injury. Grafted cells differentiated into multiple cellular phenotypes, including neurons, which extended large numbers of axons over remarkable distances. Extending axons formed abundant synapses with host cells. Axonal growth was partially dependent on mammalian target of rapamycin (mTOR) but not Nogo signaling. Grafted neurons supported formation of electrophysiological relays across sites of complete spinal transection, resulting in functional recovery. Two human stem cell lines (566RSC and HUES7) embedded in growth factor-containing fibrin exhibited similar growth, and 566RSC cells supported functional recovery. Thus, properties intrinsic to early stage neurons can overcome the inhibitory milieu of the injured adult spinal cord to mount remarkable axonal growth resulting in formation of novel relay circuits that significantly improve function. These therapeutic properties extend across stem cell sources and species.
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