Endothelial precursor cells stimulate pericyte-like coverage of bone marrow-derived mesenchymal stem cells through platelet-derived growth factor-BB induction, which is enhanced by substance P

OBJECTIVE: The aim of this study was to evaluate the angiogenicity of a combination of BM-EPCs and BM-MSCs in vitro in the presence of SP and its working mechanism. METHODS: BM-MSCs and BM-EPCs were cocultured with or without SP. ELISA and RT-PCR were performed to detect angiogenic factors such as VEGF and PDGF-BB. N-cadherin was detected by Western blot analysis. The tubular network-forming ability was evaluated by a Matrigel tube-forming assay. RESULTS: BM-EPCs coculture with BM-MSCs strongly stimulated the recruitment of BM-MSCs onto the BM-EPC-generated endothelial tubular network. Upon SP treatment, endothelial branching point, tubule length, and tubular recruitment of BM-MSCs were further increased and stabilized. The coculture of BM-EPCs and BM-MSCs synergistically stimulated expression of VEGF, VEGF receptor, N-cadherin, and PDGF-BB, all of which were further enhanced by SP treatment. Blockade of PDGF-BB by its functional blocking antibodies markedly reduced the BM-MSC incorporation into the endothelial tubules. SP-pretreated BM-MSCs were preferentially incorporated into the preformed BM-EPC tubular network. CONCLUSIONS: BM-EPCs along with SP promote the pericyte-like coverage of BM-MSCs on endothelial tubules possibly through the induction of PDGF-BB.