Mesenchymal stem/stromal cells enhance engraftment, vasculogenic and pro-angiogenic activities of endothelial colony forming cells in immunocompetent hosts

The clinical use of endothelial colony forming cells (ECFC) is hampered by their restricted engraftment. We aimed to assess engraftment, vasculogenic and pro-angiogenic activities of ECFC in immunocompetent (C57BL/6: WT) or immunodeficient (rag1 (−/−)C57BL/6: Rag1) mice. In addition, the impact of host immune system was investigated where ECFC were co-implanted with mesenchymal stem/stromal cells (MSC) from adult bone marrow (AdBM-MSC), fetal bone marrow (fBM-MSC), fetal placental (fPL-MSC), or maternal placental (MPL-MSC). Transplantation of ECFCs in Matrigel plugs resulted in less cell engraftment in WT mice compared to Rag1 mice. Co-implantation with different MSCs resulted in a significant increase in cell engraftment up to 9 fold in WT mice reaching levels of engraftment observed when using ECFCs alone in Rag1 mice but well below levels of engraftment with MSC-ECFC combination in Rag1 recipients. Furthermore, MSCs did not reduce murine splenic T cell proliferation in response to ECFCs in vitro. ECFCs enhanced the murine neo-vascularization through paracrine effect, but with no difference between Rag1 and WT mice. In conclusions, the host adaptive immune system affects the engraftment of ECFCs. MSC co-implantation improves ECFC engraftment and function even in immunocompetent hosts mostly through non-immune mechanisms.