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人 CD117CD90CD105 羊水干细胞对缺氧缺血性脑损伤的神经保护作用。

Neuroprotection of the hypoxic-ischemic mouse brain by human CD117CD90CD105 amniotic fluid stem cells.

机构信息

University College London, Institute for Women's Health, Maternal and Fetal Medicine Department, London, UK.

University College London, Great Ormond Street Institute for Child Health, London, UK.

出版信息

Sci Rep. 2018 Feb 5;8(1):2425. doi: 10.1038/s41598-018-20710-9.

DOI:10.1038/s41598-018-20710-9
PMID:29402914
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5799160/
Abstract

Human amniotic fluid contains two morphologically-distinct sub-populations of stem cells with regenerative potential, spindle-shaped (SS-hAFSCs) and round-shaped human amniotic fluid stem cells (RS-hAFSCs). However, it is unclear whether morphological differences correlate with functionality, and this lack of knowledge limits their translational applications. Here, we show that SS-hAFSCs and RS-hAFSCs differ in their neuro-protective ability, demonstrating that a single contralateral injection of SS-hAFSCs into hypoxic-ischemic P7 mice conferred a 47% reduction in hippocampal tissue loss and 43-45% reduction in TUNEL-positive cells in the hippocampus and striatum 48 hours after the insult, decreased microglial activation and TGFβ1 levels, and prevented demyelination. On the other hand, RS-hAFSCs failed to show such neuro-protective effects. It is possible that SS-hAFSCs exert their neuroprotection via endoglin-dependent inhibition of TGFβ1 signaling in target cells. These findings identify a sub-population of CD117CD90CD105 stem cells as a promising source for the neuro-protection of the developing brain.

摘要

人羊水含有两种具有再生潜力的形态上不同的干细胞亚群,即纺锤形(SS-hAFSCs)和圆形人羊水干细胞(RS-hAFSCs)。然而,目前尚不清楚形态差异是否与功能相关,这种知识的缺乏限制了它们的转化应用。在这里,我们表明 SS-hAFSCs 和 RS-hAFSCs 在神经保护能力上存在差异,表明 P7 缺氧缺血小鼠对侧单次注射 SS-hAFSCs 可使海马组织损失减少 47%,海马和纹状体中 TUNEL 阳性细胞减少 43-45%,48 小时后损伤,减少小胶质细胞活化和 TGFβ1 水平,并防止脱髓鞘。另一方面,RS-hAFSCs 未能显示出这种神经保护作用。SS-hAFSCs 可能通过靶细胞中内格兰蛋白依赖性 TGFβ1 信号抑制发挥其神经保护作用。这些发现确定了 CD117CD90CD105 干细胞的一个亚群作为发育中大脑神经保护的有希望的来源。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ad9/5799160/660fd4dde7a0/41598_2018_20710_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ad9/5799160/660fd4dde7a0/41598_2018_20710_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ad9/5799160/5b4269f2a9d7/41598_2018_20710_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ad9/5799160/660fd4dde7a0/41598_2018_20710_Fig7_HTML.jpg

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