Human Periosteum-Derived Stem Cells for Tissue Engineering Applications: The Role of VEGF

Mesenchymal stem cells (MSCs) are promising tools for studying the mechanisms of development and for the regeneration of injured tissues. Correct selection of the MSCs source is crucial in order to obtain a more efficient treatment and, in this respect Periosteum-Derived Cells (PDPCs) may represent an interesting alternative to bone marrow MSCs for osteochondral tissue regeneration. In the present study we have isolated and characterized a MSCs population from the periosteum of human adult donors. PDPCs were expanded under specific culture conditions that prevent fibroblast contamination and support the maintenance of their undifferentiated phenotype. We show, for the first time, that PDPCs expresses VEGF receptor (Flt1 and KDR/Flk1) proteins and that they were similar to bone marrow Multipotent Adult Progenitor Cells (MAPCs). Since the latter are able to differentiate into endothelial cells, we tested the possible PDPCs commitment toward an endothelial phenotype in view of bone tissue engineering approaches that takes into account not only bone formation but also vascularization. PDPCs were treated with two different VEGF concentrations for 7 and 15 days and, alternatively, with the supernatant of human primary osteoblasts. Differently from MAPCs our PDPCs were unable to differentiate into endothelial cells after their in vitro VEGF treatment. On the contrary, growth factor stimulation induces PDPCs differentiation toward osteoblasts. We concluded that in PDPCs the presence of VEGF receptors is related to different cross-talk between osteogenesis and angiogenesis that could involve in situ PDPCs recruitment.