Angiogenesis in differentiated placental multipotent mesenchymal stromal cells is dependent on integrin alpha5beta1.

Abstract

Human placental multipotent mesenchymal stromal cells (hPMSCs) can be isolated from term placenta, but their angiogenic ability and the regulatory pathways involved are not known. hPMSCs were shown to express integrins alpha(v), alpha(4), alpha(5), beta(1), beta(3), and beta(5) and could be induced to differentiate into cells expressing endothelial markers. Increases in cell surface integrins alpha(5) and beta(1), but not alpha(4), alpha(v)beta(3), or alpha(v)beta(5), accompanied endothelial differentiation. Vascular endothelial growth factor-A augmented the effect of fibronectin in enhancing adhesion and migration of differentiated hPMSC through integrin alpha(5)beta(1), but not alpha(v)beta(3) or alpha(v)beta(5). Formation of capillary-like structures in vitro from differentiated cells was inhibited by pre-treatment with function-blocking antibodies to integrins alpha(5) and beta(1). When hPMSCs were seeded onto chick chorioallantoic membranes (CAM), human von Willebrand factor-positive cells were observed to engraft in the chick endothelium. CAMs transplanted with differentiated hPMSCs had a greater number of vessels containing human cells and more incorporated cells per vessel compared to CAMs transplanted with undifferentiated hPMSCs, and overall angiogenesis was enhanced more by the differentiated cells. Function-blocking antibodies to integrins alpha(5) and beta(1) inhibited angiogenesis in the CAM assay. These results suggest that differentiated hPMSCs may contribute to blood vessel formation, and this activity depends on integrin alpha(5)beta(1).