Transplantation of neural scaffolds consisting of dermal fibroblast-reprogrammed neurons and 3D silk fibrous materials promotes the repair of spinal cord injury
Transplantation of neural scaffolds consisting of dermal fibroblast-reprogrammed neurons and 3D silk fibrous materials promotes the repair of spinal cord injury
复制标题
移植由真皮成纤维细胞重编程神经元和3D丝纤维材料组成的神经支架促进脊髓损伤的修复
DOI：
10.1039/c9tb01929d
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发表时间：
2019-12-21
影响因子：
7
通讯作者：
Zhang, Huanxiang
中科院分区：
文献类型：
--
作者：
Hu, Ya'nan;Zhang, Feng;Zhang, Huanxiang
组织工程神经支架移植在脊髓损伤后神经回路重建中具有巨大的潜力。本研究制备了一种三维多孔丝纤维支架（3D-SF），该支架具有仿生互连的微-纳米纤维结构和良好的生物相容性。然后，筛选了有效地将大鼠真皮成纤维细胞重编程为神经元的小分子组合CFLSSVY（CHIR 99021、Forskolin、LDN 193189、SB 431542、SP 600125、VPA和Y27632），并且这些化学诱导的神经元（CiN）显示出容易在3D-SF上通信并形成神经支架。将这些基于丝的神经支架移植到大鼠脊髓横断残端后，损伤组织得到显著修复，如损伤部位的空腔面积减少、GFAP表达降低以及轴突再生和髓鞘形成改善所示。BBB评分升高，45 °斜格试验中双后肢交替运动，cMEP检测潜伏期缩短，波幅增强，表明后肢运动和运动神经传导性明显改善。总之，这些结果表明，由3D-SF和真皮成纤维细胞重编程神经元组成的神经支架移植导致显著的神经再生和功能恢复，为SCI提供了一种有前途的治疗策略。
Transplantation of tissue-engineered neural scaffolds bears great potential for reconstructing neural circuits after spinal cord injury (SCI). In this study, a 3D porous silk fibrous scaffold (3D-SF) with biomimetic interconnected micro- to nanofibrous structure and good biocompatibility is fabricated. Then, a small-molecule combination CFLSSVY (CHIR99021, Forskolin, LDN193189, SB431542, SP600125, VPA, and Y27632) that efficiently reprograms rat dermal fibroblasts into neurons is screened, and these chemically induced neurons (CiNs) are shown to readily communicate on the 3D-SF and form neural scaffolds. After transplantation of these silk-based neural scaffolds into the stumps of transected spinal cords in rats, the damaged tissue is repaired significantly, as indicated by the reduced cavity areas, decreased GFAP expression, and improved axonal regeneration and myelination in the injury site. Moreover, the hindlimb movement and motor-nerve conductivity are greatly improved as indicated by the elevated BBB score, the alternate movement of two hindlimbs during the 45 degrees inclined grid test, and the shortened latency and enhanced amplitude in cMEP detection. Together, these results demonstrate that transplantation of neural scaffolds consisting of 3D-SF and dermal fibroblast-reprogrammed neurons leads to significant nerve regeneration and functional recovery, providing a promising therapeutic strategy for SCI.