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人脐带间充质干细胞表达优先分泌与神经保护、神经发生和血管生成相关的因子。

Mesenchymal stem cells from human umbilical cord express preferentially secreted factors related to neuroprotection, neurogenesis, and angiogenesis.

机构信息

Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.

出版信息

PLoS One. 2013 Aug 22;8(8):e72604. doi: 10.1371/journal.pone.0072604. eCollection 2013.

Abstract

Mesenchymal stem cells (MSCs) are promising tools for the treatment of diseases such as infarcted myocardia and strokes because of their ability to promote endogenous angiogenesis and neurogenesis via a variety of secreted factors. MSCs found in the Wharton's jelly of the human umbilical cord are easily obtained and are capable of transplantation without rejection. We isolated MSCs from Wharton's jelly and bone marrow (WJ-MSCs and BM-MSCs, respectively) and compared their secretomes. It was found that WJ-MSCs expressed more genes, especially secreted factors, involved in angiogenesis and neurogenesis. Functional validation showed that WJ-MSCs induced better neural differentiation and neural cell migration via a paracrine mechanism. Moreover, WJ-MSCs afforded better neuroprotection efficacy because they preferentially enhanced neuronal growth and reduced cell apoptotic death of primary cortical cells in an oxygen-glucose deprivation (OGD) culture model that mimics the acute ischemic stroke situation in humans. In terms of angiogenesis, WJ-MSCs induced better microvasculature formation and cell migration on co-cultured endothelial cells. Our results suggest that WJ-MSC, because of a unique secretome, is a better MSC source to promote in vivo neurorestoration and endothelium repair. This study provides a basis for the development of cell-based therapy and carrying out of follow-up mechanistic studies related to MSC biology.

摘要

间充质干细胞(MSCs)因其能够通过多种分泌因子促进内源性血管生成和神经发生,因此成为治疗心肌梗死和中风等疾病的有前途的工具。从人脐带华通氏胶中分离出的 MSC 易于获得,并且可以进行移植而不会发生排斥反应。我们分别从华通氏胶和骨髓中分离出 MSC(分别称为 WJ-MSC 和 BM-MSC),并比较了它们的分泌组。结果发现,WJ-MSC 表达了更多参与血管生成和神经发生的基因,尤其是分泌因子。功能验证表明,WJ-MSC 通过旁分泌机制诱导更好的神经分化和神经细胞迁移。此外,WJ-MSC 还能提供更好的神经保护作用,因为它们在模拟人类急性缺血性中风情况的氧葡萄糖剥夺(OGD)培养模型中,优先增强原代皮质细胞的神经元生长并减少细胞凋亡死亡。在血管生成方面,WJ-MSC 诱导共培养的内皮细胞形成更好的微血管和细胞迁移。我们的研究结果表明,由于独特的分泌组,WJ-MSC 是一种更好的 MSC 来源,可促进体内神经修复和内皮修复。本研究为基于细胞的治疗方法的发展以及与 MSC 生物学相关的后续机制研究提供了依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80d0/3749979/d2756b0cb57a/pone.0072604.g001.jpg

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