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.
Keywords: 3D; Angiogenesis; BMSC; EC; Fibrin; HUVEC; MSC; Mesenchymal stem cell; Microenvironment; NG2; NSC; alpha-smooth muscle actin; bone marrow-derived mesenchymal stem cell; endothelial cell; human umbilical vein endothelial cell; mesenchymal stem cell; neural stem cell; neuron-glial antigen 2; shRNA; small hairpin RNA; three-dimensional; α6β1 Integrin; αSMA.
© 2013 Published by Elsevier Inc.