Lin Cho-Hao, Lilly Brenda
Department of Pediatrics, The Heart Center, Nationwide Children's Hospital, The Ohio State University , Columbus, Ohio.
Stem Cells Dev. 2014 Nov 1;23(21):2581-90. doi: 10.1089/scd.2014.0163. Epub 2014 Jul 14.
Under defined conditions, mesenchymal stem cells can differentiate into unique cell types, making them attractive candidates for cell-based disease therapies. Ischemic diseases would greatly benefit from treatments that include the formation of new blood vessels from mesenchymal stem cells. However, blood vessels are complex structures composed of endothelial cells and smooth muscle cells, and their assembly and function in a diseased environment is reliant upon joining with the pre-existing vasculature. Although endothelial cell/smooth muscle cell interactions are well known, how endothelial cells may influence mesenchymal stem cells and facilitate their differentiation has not been defined. Therefore, we sought to explore how endothelial cells might drive mesenchymal stem cells toward a smooth muscle fate. Our data show that cocultured endothelial cells induce smooth muscle cell differentiation in mesenchymal stem cells. Endothelial cells can promote a contractile phenotype, reduce proliferation, and enhance collagen synthesis and secretion. Our data show that Notch signaling is essential for endothelial cell-dependent differentiation, and this differentiation pathway is largely independent of growth factor signaling mechanisms.
在特定条件下，间充质干细胞可分化为独特的细胞类型，使其成为基于细胞的疾病治疗的有吸引力的候选者。缺血性疾病将极大地受益于包括由间充质干细胞形成新血管的治疗方法。然而，血管是由内皮细胞和平滑肌细胞组成的复杂结构，它们在患病环境中的组装和功能依赖于与预先存在的脉管系统相连。尽管内皮细胞/平滑肌细胞相互作用是众所周知的，但内皮细胞如何影响间充质干细胞并促进其分化尚未明确。因此，我们试图探索内皮细胞如何驱动间充质干细胞走向平滑肌命运。我们的数据表明，共培养的内皮细胞可诱导间充质干细胞向平滑肌细胞分化。内皮细胞可促进收缩表型，减少增殖，并增强胶原蛋白的合成和分泌。我们的数据表明，Notch信号对于内皮细胞依赖性分化至关重要，并且这种分化途径在很大程度上独立于生长因子信号机制。
