Training Neural Stem Cells on Functional Collagen Scaffolds for Severe Spinal Cord Injury Repair
Training Neural Stem Cells on Functional Collagen Scaffolds for Severe Spinal Cord Injury Repair
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DOI：
10.1002/adfm.201601521
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发表时间：
2016-08-23
影响因子：
19
通讯作者：
Dai, Jianwu
中科院分区：
文献类型：
--
作者：
Li, Xing;Liu, Sumei;Dai, Jianwu
神经干细胞移植被认为是治疗严重脊髓损伤（SCI）的一种有前途的治疗策略。然而，移植的神经干细胞及其后代在宿主脊髓内的长期存活、定向神经元分化和功能整合等重大挑战仍有待解决。在这项研究中，神经干细胞在不同改性的胶原支架上训练，以增加在模拟SCI微环境下培养时的神经元分化率。然后筛选出一种功能性支架，在此支架上培养的神经干细胞表现出高的神经元分化率，并产生感觉和运动成熟神经元。随后，将NSC接种的功能支架移植到大鼠严重SCI模型中。结果表明，移植的神经干细胞具有较高的内源性神经发生效率、体内存活率和神经元分化率。此外，感觉和运动神经元被发现分化从移植的神经干细胞在病变部位和那些新产生的神经元可以在功能上相互作用，并与宿主神经元。总之，用于调节神经干细胞分化谱的体外训练系统具有指导意义，并显示出用于SCI治疗的强大潜力。
Neural stem cells (NSCs) transplantation is regarded as a promising therapeutic strategy to treat severe spinal cord injury (SCI) by compensating the neuronal loss. However, signifi cant challenges including long-term survival, directed neuronal differentiation, and functional integration of the transplanted NSCs and their progenies within the host spinal cord are yet to be solved. In this study, NSCs are trained on differently modified collagen scaffolds to increase their neuronal differentiation rate when cultured under the simulated SCI microenvironment. Then, a functional scaffold is screened out, on which the cultured NSCs show high neuronal differentiation rate and generate both sensory and motor mature neurons. Subsequently, that NSC seeded functional scaffold is transplanted into a rat severe SCI model. The results show that higher endogenous neurogenesis efficiency as well as in vivo survival and neuronal differentiation rate of the grafted NSCs are observed. Moreover, both sensory and motor neurons are found to be differentiated from the grafted NSCs in the lesion site and those newly generated neurons can functionally interact with each other and the host neurons. Taken together, the in vitro training systems for modulating the differentiation profiles of NSCs are instructive and exhibit strong potentials for SCI treatments.