Human Fetal Cardiac Mesenchymal Stromal Cells Differentiate In Vivo into Endothelial Cells and Contribute to Vasculogenesis in Immunocompetent Mice

Mesenchymal stromal cells (MSCs) have shown great potential as a treatment for systemic inflammatory diseases, but their local regenerative properties are highly tissue- and site specific. Previous studies have demonstrated that adult human MSCs respond to inflammatory cytokines through the release of paracrine factors that stimulate angiogenesis, but they do not themselves differentiate into vascular structures in vivo. In this study, we used human fetal cardiac MSCs (hfcMSCs) harvested during the first trimester of heart development and injected them into the subcutaneous tissue of normal immunocompetent mice treated with short-term costimulation blockade for tolerance induction. When hfcMSCs were transplanted subcutaneously together with Matrigel matrix, they contributed to vasculogenesis through differentiation into endothelial cells and generation of the basal membrane protein Laminin α4. These characteristics of hfcMSCs are similar to the mesodermal progenitors giving rise to the developing heart and they may be useful for treatment of ischemic injuries.