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人牙髓间充质干细胞通过分泌抗炎和神经营养因子保护大鼠视神经切断后的视网膜神经节细胞。

Human Wharton's jelly mesenchymal stem cells protect axotomized rat retinal ganglion cells via secretion of anti-inflammatory and neurotrophic factors.

机构信息

Unidad de Terapia Celular y Trasplante Hematopoyético. Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain.

Dpto Medicina Interna, Universidad de Murcia, Murcia, Spain.

出版信息

Sci Rep. 2018 Nov 2;8(1):16299. doi: 10.1038/s41598-018-34527-z.

Abstract

Mesenchymal stem cell (MSC) transplantation is emerging as an ideal tool to restore the wounded central nervous system (CNS). MSCs isolated from extra-embryonic tissues have some advantages compared to MSCs derived from adult ones, such as an improved proliferative capacity, life span, differentiation potential and immunomodulatory properties. In addition, they are more immunoprivileged, reducing the probability of being rejected by the recipient. Umbilical cords (UCs) are a good source of MSCs because they are abundant, safe, non-invasively harvested after birth and, importantly, they are not encumbered with ethical problems. Here we show that the intravitreal transplant of Wharton´s jelly mesenchymal stem cells isolated from three different human UCs (hWJMSCs) delays axotomy-induced retinal ganglion cell (RGC) loss. In vivo, hWJMSCs secrete anti-inflammatory molecules and trophic factors, the latter alone may account for the elicited neuroprotection. Interestingly, this expression profile differs between naive and injured retinas, suggesting that the environment in which the hWJMSCs are modulates their secretome. Finally, even though the transplant itself is not toxic for RGCs, it is not innocuous as it triggers a transient but massive infiltration of Iba1cells from the choroid to the retina that alters the retinal structure.

摘要

间充质干细胞(MSC)移植作为一种修复中枢神经系统(CNS)损伤的理想工具正在兴起。与来源于成体的 MSC 相比,来源于胚胎外组织的 MSC 具有一些优势,例如增殖能力、寿命、分化潜能和免疫调节特性的提高。此外,它们具有更高的免疫特权,降低了被受体排斥的可能性。脐带(UCs)是 MSC 的良好来源,因为它们丰富、安全、可以在出生后非侵入性地采集,而且重要的是,它们没有伦理问题。在这里,我们证明了从三个不同的人脐带(hWJMSCs)中分离的玻璃体腔内注射 Wharton 胶间充质干细胞移植可延迟轴突切断诱导的视网膜神经节细胞(RGC)丢失。在体内,hWJMSCs 分泌抗炎分子和营养因子,后者可能单独解释了诱导的神经保护作用。有趣的是,这种表达谱在未损伤和损伤的视网膜之间存在差异,这表明 hWJMSCs 所处的环境会调节它们的分泌组。最后,尽管移植本身对 RGC 没有毒性,但它并不是无害的,因为它会引发脉络膜到视网膜的 Iba1 细胞的短暂但大量浸润,从而改变视网膜结构。

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