Bone marrow-derived mesenchymal stem cells enhance angiogenesis via their [alpha]6[beta]1 integrin receptor.
Carrion, Bita a; Kong, Yen P. a; Kaigler, Darnell a,b; Putnam, Andrew J. a,*
[Article] Experimental Cell Research. 319(19):2964-2976, November 2013.

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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 [alpha]6[beta]1 integrin adhesion receptor on BMSCs in sprouting angiogenesis. We report that knockdown of the [alpha]6 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 [alpha]6 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 [alpha]6 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.

* BMSCs stimulate angiogenesis, but the mechanisms remain unclear.

* We silenced the expression of the [alpha]6 integrin subunit in BMSCs.

* Silencing this receptor subunit significantly inhibited angiogenic sprouting.

* Knocking down [alpha]6 integrin affected laminin and [alpha]SMA expression.

* Silencing [alpha]6 integrin expression also reduced BMSC proliferation.

(C) 2013Elsevier, Inc.