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使用复合3D支架结合丙戊酸诱导将间充质干细胞分化为神经元样细胞。

Differentiation of mesenchymal stem cells into neuron-like cells using composite 3D scaffold combined with valproic acid induction.

作者信息

Ghorbani Sadegh, Tiraihi Taki, Soleimani Masoud

机构信息

1 Department of Anatomical Sciences, 48503 School of Medical Sciences, Tarbiat Modares University , Tehran, Islamic Republic of Iran.

2 Department of Hematology, 48503 School of Medical Sciences, Tarbiat Modares University , Tehran, Islamic Republic of Iran.

出版信息

J Biomater Appl. 2018 Jan;32(6):702-715. doi: 10.1177/0885328217741903. Epub 2017 Nov 23.

Abstract

The nervous system has little capacity for self-repair after injury because neurons cannot proliferate owing to lack of suitable microenvironment. Therefore, neural tissue engineering that combines neural stem, scaffolds, and growth factors may improve the chance of restoration of damaged neural tissues. A favorable niche for neural regeneration would be both fibrous and electrically conductive scaffolds. Human Wharton jelly-derived mesenchymal stem cells were seeded on wet-electrospun 3D scaffolds composed of poly lactic acid coated with natural polymers including alginate and gelatin, followed by a multi-wall carbon nanotube coating. The results show that a wet-electrospun poly lactic acid scaffold at a concentration of 15% w/v had higher porosity (above 80%) than other concentrations. Moreover, the coated scaffold supported the growth of human Wharton jelly-derived mesenchymal stem cells in 3D culture, and were incubated for 21 days with 1 mM valproic acid as the inducer resulted in improvement in human Wharton jelly-derived mesenchymal stem cells differentiation into neuron-like cells immunoreactivity to nestin, Map2, and neuron specific enolase (NSE), which were also consistent with reverse transcription polymerase chain reaction (RT-PCR) and quantitive Reverse transcription polymerase chain reaction (qRT-PCR) results. The conclusion is that the 3D composite nanofiber poly lactic acid scaffold improved the transdifferentiation of human Wharton jelly-derived mesenchymal stem cells into neuron-like cells.

摘要

由于缺乏合适的微环境,神经元无法增殖,因此神经系统在损伤后自我修复的能力有限。因此,结合神经干细胞、支架和生长因子的神经组织工程可能会提高受损神经组织恢复的机会。有利于神经再生的微环境将是纤维状且导电的支架。将人脐带华通氏胶间充质干细胞接种在由聚乳酸涂覆有包括藻酸盐和明胶在内的天然聚合物组成的湿电纺3D支架上,随后进行多壁碳纳米管涂层。结果表明,浓度为15% w/v的湿电纺聚乳酸支架比其他浓度具有更高的孔隙率(高于80%)。此外,涂覆后的支架支持人脐带华通氏胶间充质干细胞在3D培养中的生长,并且以1 mM丙戊酸作为诱导剂孵育21天导致人脐带华通氏胶间充质干细胞向神经元样细胞分化,对巢蛋白、微管相关蛋白2(Map2)和神经元特异性烯醇化酶(NSE)具有免疫反应性,这也与逆转录聚合酶链反应(RT-PCR)和定量逆转录聚合酶链反应(qRT-PCR)结果一致。结论是,3D复合纳米纤维聚乳酸支架改善了人脐带华通氏胶间充质干细胞向神经元样细胞的转分化。

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