Exosomes derived from human umbilical vein endothelial cells promote neural stem cell expansion while maintain their sternness in culture
Exosomes derived from human umbilical vein endothelial cells promote neural stem cell expansion while maintain their sternness in culture
复制标题
源自人脐静脉内皮细胞的外泌体促进神经干细胞扩增，同时保持其在培养物中的稳定性
DOI：
10.1016/j.bbrc.2017.11.092
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发表时间：
2018-01-01
影响因子：
3.1
通讯作者：
Han, Hua
中科院分区：
文献类型：
--
作者：
Zhang, Yi-Zhe;Liu, Fan;Han, Hua
成年哺乳动物脑室下区(SVZ)的神经干细胞(NSC)巢内含有致密的血管丛，内皮细胞(ECs)通过释放大量的血管分泌因子对NSC进行调节。然而，作为一种新型的细胞间通讯媒介，内皮细胞衍生的外切体在神经干细胞调控中的作用尚不清楚。在目前的研究中，从胚胎小鼠脑中分离的原代神经干细胞在人脐静脉内皮细胞(HUVECs)存在下培养时形成更多的神经球。当加入外切体形成阻断剂GW4869时，内皮细胞在共培养中的支持作用明显减弱，这表明HUVECs来源的外切体在支持神经干细胞方面发挥了重要作用。为了研究内皮细胞来源的外切体在神经干细胞中的作用，我们收集了人脐静脉内皮细胞的外切体。我们发现，人脐静脉内皮细胞来源的外切体能够显著促进原代培养的小鼠神经干细胞形成神经球。EDU掺入和TUNEL检测表明，在HUVECs来源的外切体存在的情况下，NSCs的增殖增加，而凋亡减少。神经干细胞与人脐静脉内皮细胞来源的外切体孵育后，保持了其多向分化潜能。严厉相关基因表达上调。提示内皮细胞来源的外切体可能在NSC生态位中发挥重要作用，可作为NSC体外扩增的试剂用于医学应用。(C)爱思唯尔公司出版的2017年。
The neural stem cell (NSC) niche in subventricular zone (SVZ) of adult mammalian brain contains dense vascular plexus, where endothelial cells (ECs) regulate NSCs by releasing plenty of angiocrine factors. However, the role of ECs-derived exosomes, a novel type of mediators of intercellular communications, in the regulation of NSCs remains unclear. In the current study, primary NSCs isolated from embryonic mouse brains form more neurospheres when cultured in the presence of human umbilical vein endothelial cells (HUVECs). The supportive role of ECs in the coculture was significantly attenuated when GW4869, a blocker of exosome formation, was included, suggesting that HUVECs-derived exosomes played a significant role in supporting NSCs. In order to investigate the role of ECs-derived exosomes on NSCs, we collected exosomes from HUVECs. We found that HUVECs-derived exosomes could significantly promote the formation of neurospheres by primary murine NSCs. EdU incorporation and TUNEL assays indicated that the proliferation of NSCs increased while apoptosis decreased when cultured in the presence of HUVECs-derived exosomes. NSCs incubated with the HUVECs-derived exosomes maintained their potential of multi-lineage differentiation potentials. The expression of sternness-related genes was up-regulated. These data suggested that ECs-derived exosomes could play an importantly role in NSC niche, and they might be used as a reagent for ex vivo NSC amplification for medical application. (C) 2017 Published by Elsevier Inc.