EMSCs Build an All-in-One Niche via Cell-Cell Lipid Raft Assembly for Promoted Neuronal but Suppressed Astroglial Differentiation of Neural Stem Cells
EMSCs Build an All-in-One Niche via Cell-Cell Lipid Raft Assembly for Promoted Neuronal but Suppressed Astroglial Differentiation of Neural Stem Cells
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EMSCs通过细胞-细胞脂筏组装构建一体化生态位,促进神经元分化但抑制神经干细胞的星形胶质细胞分化
DOI:
10.1002/adma.201806861
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发表时间:
2019-03-08
影响因子:
29.4
通讯作者:
Zhang, Zhijian
中科院分区:
文献类型:
--
作者:
Deng, Wenwen;Shao, Fengxia;Zhang, Zhijian
The therapeutic efficiency of allogenic/intrinsic neural stem cells (NSCs) after spinal cord injury is severely compromised because the hostile niche at the lesion site incurs massive astroglial but not neuronal differentiation of NSCs. Although many attempts are made to reconstruct a permissive niche for nerve regeneration, solely using a living cell material to build an all-in-one, multifunctional, permissive niche for promoting neuronal while inhibiting astroglial differentiation of NSCs is not reported. Here, ectomesenchymal stem cells (EMSCs) are reported to serve as a living, smart material that creates a permissive, all-in-one niche which provides neurotrophic factors, extracellular matrix molecules, cell-cell contact, and favorable substrate stiffness for directing NSC differentiation. Interestingly, in this all-in-one niche, a corresponding all-in-one signal-sensing platform is assembled through recruiting various niche signaling molecules into lipid rafts for promoting neuronal differentiation of NSCs, and meanwhile, inhibiting astrocyte overproliferation through the connexin43/YAP/14-3-3 theta pathway. In vivo studies confirm that EMSCs can promote intrinsic NSC neuronal differentiation and domesticating astrocyte behaviors for nerve regeneration. Collectively, this study represents an all-in-one niche created by a single-cell material-EMSCs for directing NSC differentiation.