Kidney-derived mesenchymal stem cells contribute to vasculogenesis, angiogenesis and endothelial repair.

Kidney-derived mesenchymal stem cells contribute to vasculogenesis, angiogenesis and endothelial repair.
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DOI:
10.1038/ki.2008.304
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发表时间:
2008-10
影响因子:
19.6
通讯作者:
Goligorsky, Michael S.
Goligorsky, Michael S.
中科院分区:
医学1区
文献类型:
--
作者:
Chen, Jun;Park, Hyeong-Cheon;Addabbo, Francesco;Ni, Jie;Pelger, Edward;Li, Houwei;Plotkin, Matthew;Goligorsky, Michael S.

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我们从小鼠肾脏中分离了一个克隆细胞系(4 E),该细胞系表达由内皮特异性Tie 2启动子控制的绿色荧光蛋白。当在三维基质胶基质中生长时,它们形成荧光毛细管网络。在体内血管生成试验中,使用生长因子耗尽基质胶植入塞促进宿主内皮细胞的适度血管生成。在含有4 E细胞的栓塞中使用血管内皮生长因子(VEGF)-A和成纤维细胞生长因子-2导致了强大的血管生成。将4 E细胞移植到急性肾缺血的小鼠中显示出在缺血肾中的选择性植入,其通过增加上皮增殖和抑制凋亡促进肾小管再生。这导致缺血后3天功能恢复加速。与对照组相比,这些小鼠的组织VEGF表达增加了5倍,但血浆VEGF水平无差异,这与更好地保存肾小管周围毛细血管相对应,这可能是由于全身4 E输注后的局部旁分泌效应。缺血1个月后,移植的4 E细胞中有9%表达绿色荧光蛋白,而有一半表达α-平滑肌肌动蛋白。我们的研究表明,肾脏间充质干细胞能够在体外和体内向内皮细胞和平滑肌细胞谱系分化,在有利的条件下支持新血管形成,并促进缺血肾脏的功能恢复。
We isolated a clonal cell line (4E) from kidneys of mice expressing green fluorescent protein controlled by the endothelial-specific Tie2 promoter. When grown in a three-dimensional matrigel matrix they formed a fluorescent capillary network. In vivo angiogenesis assays using growth factor-depleted matrigel implanted plugs promoted a moderate angiogenesis of host endothelial cells. Using vascular endothelial growth factor (VEGF)-A and fibroblast growth factor-2 in the plugs containing 4E-cells resulted in a robust vasculogenesis. Transplantation of 4E cells into mice with acute renal ischemia showed selective engraftment in the ischemic kidney which promoted tubular regeneration by increasing epithelial proliferation and inhibiting apoptosis. This resulted in an accelerated functional recovery 3 days after ischemia. These mice showed a 5-fold increase in tissue VEGF expression compared to controls, but no difference in plasma VEGF level corresponding with better preservation of peritubular capillaries, perhaps due to a local paracrine effect following systemic 4E infusion. One month after ischemia, 9% of engrafted 4E cells expressed green fluorescent protein in the peritubular region while half of them expressed α-smooth muscle actin. Our study shows that kidney mesenchymal stem cells are capable of differentiation toward endothelial and smooth muscle cell lineages in vitro and in vivo, support new blood vessel formation in favorable conditions and promote functional recovery of an ischemic kidney.
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