Angiogenic profile of hASCs and hDPSCs and theirs role on vascular stabilization

Regenerative medicine using mesenchymal stem cells (MSCs) for the purposes of tissue repair has garnered considerable public attention due to the potential of returning tissues and organs to a normal, healthy state after injury or damage has occurred. The scientific community is extensively investigating thereparative abilities of MSCs derived from various adult sources such as adipose tissue and dental pulp, nevertheless their phenotypic characteristics and biological potential remain largely unexplored. In fact,molecular profile of MSCs has not been yet well characterized because of the lack of exclusive cell markers, and potential cellular alterations caused by in vitro manipulation.A recent hypothesis suggests that MSCs and pericytes share common molecular characteristics as demonstrated also by the expression of specificmolecular markers, including CD146, CD105 and STRO-1. Because in physiological condition, perivascular cells, referred to as perycites, vascular smooth muscle cells or mural cells, envelop the surface of the vascular tube contributing to stabilization of the vessel, they could play a central role in regenerative medicine.The aim of this work has been to investigate in vitro the possible pericyte- like role of MSCsin blood vessel formation and maintenance.We used MSCs from two different origins: human adipose-derived mesenchymal stem cells (hASCs) and dental pulp stem cells (hDPSCs). Firstly, we evaluated the phenotypic profile of both, hASCs and hDPSC by flow citometry.Then we compared the morphology and angiogenic potential in both types of MSCs, alsowhen cultured in EGM-2, a specific endothelial medium used to enrich a population with endothelial-like cell phenotype. Moreover,we analysed the role of hASCs and hDPSC to support tubule formation of HUVEC in an in vitro 3D co-culture model between HUVECs and MSCs. Our preliminary results support the hypothesis that MSCs demonstrate in vitro endothelial-like and perivascular features. The conditioning of MSCs by pro-endothelial factors, produces in particular inhASCs, an enrichement of cells with endothelial-like cell phenotype as demonstrated by their sprouting ability respect to not conditioned MSCs. Moreover, both types of MSCs, when seeded on matrigel together with HUVEC in a 3D coculture model, supportedlong-term tubule stabilization. Conversely, in the absence of MSCs, after 24h HUVECs underwent apoptotic cell death. In conclusion, our findings provide new evidence about the therapeutic potential of MSCs in regenerative medicine. hASCs and hDPSCs can be directed versus a pro-angiogenic profile by mimicking the role of perycites in vascular stabilization.