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水凝胶包裹的神经干细胞移植可改善马尾损伤模型的功能恢复。

Transplantation of neural stem cells encapsulated in hydrogels improve functional recovery in a cauda equina lesion model.

机构信息

Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Biosci Trends. 2020 Nov 4;14(5):360-367. doi: 10.5582/bst.2020.03321. Epub 2020 Oct 25.

Abstract

This study explored the therapeutic effects of transplantation of neural stem cells (NSCs) encapsulated in hydrogels in a cauda equina lesion model. NSCs were isolated from neonatal dorsal root ganglion (nDRG) and cultured in three-dimensional porous hydrogel scaffolds. Immunohistochemistry, transmission electron microscopy and TUNEL assay were performed to detect the differentiation capability, ultrastructural and pathological changes, and apoptosis of NSCs. Furthermore, the functional recovery of sensorimotor reflexes was determined using the tail-flick test. NSCs derived from DRG were able to proliferate to form neurospheres and mainly differentiate into oligodendrocytes in the three-dimensional hydrogel culture system. After transplantation of NSCs encapsulated in hydrogels, NSCs differentiated into oligodendrocytes, neurons or astrocytes in vivo. Moreover, NSCs engrafted on the hydrogels decreased apoptosis and alleviated the ultrastructural and pathological changes of injured cauda equina. Behavioral analysis showed that transplanted hydrogel-encapsulated NSCs decreased the tail-flick latency and showed a neuroprotective role on injured cauda equina. Our results indicate transplantation of hydrogel-encapsulated NSCs promotes stem cell differentiation into oligodendrocytes, neurons or astrocytes and contributes to the functional recovery of injured cauda equina, suggesting that NSCs encapsulated in hydrogels may be applied for the treatment of cauda equina injury.

摘要

本研究探讨了水凝胶包封神经干细胞(NSCs)在马尾损伤模型中的治疗效果。NSCs 从新生背根神经节(nDRG)中分离出来,并在三维多孔水凝胶支架中培养。通过免疫组织化学、透射电子显微镜和 TUNEL 检测,检测 NSCs 的分化能力、超微结构和病理变化以及细胞凋亡。此外,采用尾巴闪烁试验测定感觉运动反射的功能恢复情况。DRG 来源的 NSCs 能够增殖形成神经球,并在三维水凝胶培养系统中主要分化为少突胶质细胞。水凝胶包封的 NSCs 移植后,NSCs 在体内分化为少突胶质细胞、神经元或星形胶质细胞。此外,移植到水凝胶上的 NSCs 减少了细胞凋亡,并减轻了损伤马尾的超微结构和病理变化。行为分析表明,移植的水凝胶包封的 NSCs 降低了尾巴闪烁潜伏期,并对损伤的马尾具有神经保护作用。我们的结果表明,水凝胶包封的 NSCs 移植促进了干细胞向少突胶质细胞、神经元或星形胶质细胞的分化,并有助于损伤马尾的功能恢复,提示水凝胶包封的 NSCs 可能适用于治疗马尾损伤。

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