Bone marrow-derived mesenchymal stem cells enhance angiogenesis via their α6β1 integrin receptor.
Bone marrow-derived mesenchymal stem cells enhance angiogenesis via their α6β1 integrin receptor.
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DOI：
10.1016/j.yexcr.2013.09.007
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发表时间：
2013-11-15
影响因子：
3.7
通讯作者：
Putnam, Andrew J.
中科院分区：
文献类型：
--
作者：
Carrion, Bita;Kong, Yen P.;Kaigler, Darnell;Putnam, Andrew J.
骨髓间充质干细胞（BMSCs）部分通过旁分泌介质和稳定周细胞促进体内三维（3D）基质内和体外工程组织中内皮细胞（EC）的血管生成反应。然而，在血管生成过程中，BMSCs和新生小管之间的分子相互作用尚未完全了解。在本研究中，我们使用了一个易于处理的三维共培养模型，以探讨α6β1整合素粘附受体对骨髓基质细胞在萌芽血管生成中的功能作用。我们报道了α6整合素亚基在骨髓基质细胞中的敲除显著减少了毛细血管发芽，并导致它们不能与新生血管结合。此外，我们证明，相对于表达非靶向shRNA的对照细胞或野生型BMSC，具有减弱的α6整合素的BMSC以显著较低的速率增殖;然而，尽管添加了更多的细胞来补偿这种增殖缺陷，但缺陷的发芽仍然存在。总的来说，我们的研究结果表明，α6整合素亚基在骨髓基质细胞是重要的，他们的能力，刺激血管形态发生。这一结论可能具有重要的意义，在优化基于细胞的策略，以促进血管生成。
Bone marrow-derived mesenchymal stem cells (BMSCs) facilitate the angiogenic response of endothelial cells (ECs) within three-dimensional (3D) matrices in vivo and in engineered tissues in vitro in part through paracrine mediators and by acting as stabilizing pericytes. However, the molecular interactions between BMSCs and nascent tubules during the process of angiogenesis are not fully understood. In this study, we have used a tractable 3D co-culture model to explore the functional role of the α6β1 integrin adhesion receptor on BMSCs in sprouting angiogenesis. We report that knockdown of the α6 integrin subunit in BMSCs significantly reduces capillary sprouting, and causes their failure to associate with the nascent vessels. Furthermore, we demonstrate that the BMSCs with attenuated α6 integrin proliferate at a significantly lower rate relative to either control cells expressing non-targeting shRNA or wild type BMSCs; however, despite adding more cells to compensate for this deficit in proliferation, deficient sprouting persists. Collectively, our findings demonstrate that the α6 integrin subunit in BMSCs is important for their ability to stimulate vessel morphogenesis. This conclusion may have important implications in the optimization of cell-based strategies to promote angiogenesis.
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