期刊
BIOMATERIALS
卷 269, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2020.120479
关键词
Complete spinal cord injury; Small molecules; Collagen hydrogel; Neural stem cells; Neurogenesis; In vivo; Migration
资金
- National Natural Science Foundation of China [81891000]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA16020100, XDA16040000]
- National Key R&D Program of China [2017YFA0104701, 2017YFA0104704, 2016YFC1101501, 2016YFC1101502]
- National High Technology Research and Development Program of China (863 project) [2015AA020312]
The combination treatment of small molecules and collagen hydrogel can induce in situ endogenous NSCs to form neurons and restore damaged functions, providing a potential therapeutic strategy for SCI.
Complete spinal cord injury (SCI) leads to cell death, interruption of axonal connections and permanent functional impairments. In the development of SCI treatments, cell transplantation combined with biomaterial-growth factor-based therapies have been widely studied. Another avenue worth exploring is the generation of neurons from endogenous neural stem cells (NSCs) or reactive astrocytes activated by SCI. Here, we screened a combination of four small molecules, LDN193189, SB431542, CHIR99021 and P7C3-A20, that can increase neuronal differentiation of mouse and rat spinal cord NSCs. Moreover, the small molecules loaded in an injectable collagen hydrogel induced neurogenesis and inhibited astrogliogenesis of endogenous NSCs in the injury site, which usually differentiate into astrocytes under pathological conditions. Meanwhile, induced neurons migrated into the non-neural lesion core, and genetic fate mapping showed that neurons mainly originated from NSCs in the parenchyma, but not from the central canal of the spinal cord. The neuronal regeneration in the lesion sites resulted in some recovery of locomotion. Our findings indicate that the combined treatment of small molecules and collagen hydrogel is a potential therapeutic strategy for SCI by inducing in situ endogenous NSCs to form neurons and restore damaged functions.
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