Neuroprotection of the hypoxic-ischemic mouse brain by human CD117(+)CD90(+)CD105(+) amniotic fluid stem cells.

Neuroprotection of the hypoxic-ischemic mouse brain by human CD117(+)CD90(+)CD105(+) amniotic fluid stem cells.
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DOI:
10.1038/s41598-018-20710-9
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发表时间:
2018-02-05
期刊:
影响因子:
4.6
通讯作者:
Guillot PV
Guillot PV
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Corcelli M;Hawkins K;Vlahova F;Hunjan A;Dowding K;De Coppi P;David AL;Peebles D;Gressens P;Hagberg H;Hristova M;Guillot PV

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人羊水含有两种形态上不同的具有再生潜能的干细胞亚群,纺锤形(SS-hAFSC)和圆形人羊水干细胞(RS-hAFSC)。然而,目前还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翻译应用。在这里,我们发现SS-hAFSC和RS-hAFSC在神经保护能力上不同,证明在缺氧缺血性P7小鼠中单次对侧注射SS-hAFSC,在损伤后48小时,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%,降低小胶质细胞活化和TGFβ1水平,并防止脱髓鞘。另一方面,RS-hAFSC未能显示出这种神经保护作用。SS-hAFSC可能通过内皮素依赖性抑制靶细胞中的TGFβ1信号传导来发挥其神经保护作用。这些发现确定了CD 117 + CD 90 + CD 105+干细胞亚群作为发育中大脑神经保护的有希望的来源。
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 CD117+CD90+CD105+ stem cells as a promising source for the neuro-protection of the developing brain.
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