Silva Eduardo A, Eseonu Chikezie, Mooney David J
Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA, USA.
Angiogenesis. 2014 Jul;17(3):617-30. doi: 10.1007/s10456-014-9414-9. Epub 2014 Jan 11.
The sprouting of endothelial cells from pre-existing blood vessels represents a critical event in the angiogenesis cascade. However, only a fraction of cultured or transplanted endothelial cells form new vessels. Moreover, it is unclear whether this results from a stochastic process or instead relates to certain endothelial cells having a greater angiogenic potential. This study investigated whether there exists a sub-population of cultured endothelial cells with enhanced angiogenic potency in vitro and in vivo. First, endothelial cells that participated in sprouting, and non-sprouting cells, were separately isolated from a 3D fibrin gel sprouting assay. Interestingly, the sprouting cells, when placed back into the same assay, displayed a sevenfold increase in the number of sprouts, as compared to control cells. Angiotensin-converting enzyme (CD143) was significantly down regulated on sprouting cells, as compared to regular endothelial cells. A subset of endothelial cells with low CD143 expression was then prospectively isolated from an endothelial cell culture. Finally, these cells were found to have greater potency in alleviating local ischemia, and restoring regional blood perfusion when transplanted into ischemic hindlimbs, as compared to unsorted endothelial cells. In summary, this study indicates that low expression of CD143 can be used as a biomarker to identify an endothelial cell sub-population that is more capable to drive neovascularization.
从已有的血管中内皮细胞的芽生是血管生成级联反应中的一个关键事件。然而，只有一小部分培养的或移植的内皮细胞能形成新血管。此外，尚不清楚这是由随机过程导致的，还是与某些具有更大血管生成潜力的内皮细胞有关。本研究调查了体外和体内培养的内皮细胞中是否存在具有增强血管生成能力的亚群。首先，从三维纤维蛋白凝胶芽生试验中分别分离出参与芽生的内皮细胞和未芽生的细胞。有趣的是，与对照细胞相比，将芽生细胞放回相同试验中时，其芽生数量增加了七倍。与正常内皮细胞相比，芽生细胞上的血管紧张素转换酶（CD143）明显下调。然后从内皮细胞培养物中前瞻性地分离出CD143表达低的内皮细胞亚群。最后，与未分选的内皮细胞相比，发现这些细胞在移植到缺血后肢时，在减轻局部缺血和恢复局部血流灌注方面具有更大的能力。总之，本研究表明CD143的低表达可作为一种生物标志物，用于识别更有能力驱动新血管形成的内皮细胞亚群。
