The role of single cell derived vascular resident endothelial progenitor cells in the enhancement of vascularization in scaffold-based skin regeneration

Artículo de publicación ISIIncreasing evidence suggests that vascular resident endothelial progenitor cells (VR-EPCs) are present in several organs, playing an important role in postnatal neovascularization. Here, we isolated and characterized VR-EPCs from cardiac tissue in vitro, evaluating their regenerative potential in vivo. VR-EPCs showed to be highly clonogenic and expressed several stem and differentiation markers. Under endothelial differentiation conditions, cells form capillary-like structures, in contrast to osteogenic or adipogenic differentiation conditionswhere no functional changes were observed. After seeding in scaffolds, cells were distributed homogeneously and directly attached to the scaffold. Then, cell seeded scaffolds were used to induce dermal regeneration in a nude mice full skin defect model. The presence of VR-EPCs enhanced dermal vascularization. Histological assays showed increased vessel number (p < 0.05) and cellularization (p < 0.05) in VR-EPCs group. In order to explore possible mechanisms of vascular regeneration, in vitro experiments were performed. Results showed that pro-angiogenic environments increased the migration capacity (p < 0.001) and ability to formcapillary-like structures (p < 0.05) of VR-EPC. In addition, VR-EPCs secreted several pro-angiogenic molecules including VEGF and PDGF. These results indicate that a highly clonogenic population of VR-EPCs might be established in vitro, representing a new source for therapeutic vascularization in tissue engineering and regeneration.This work was supported by grants from University Hospital rechts der Isar, Technische Universität München To HGM; a clinic research grant from Technische Universität München to ZZ (KKF. No. 8744556); German Research Council (DFG) IT-13/1, IT- 13/2 and IT-13/3 to WDI; European Regional Development Fund (ERDF) to CK and FONDAP (Nr. 15090007) to JTE. Z.Z was supported by a scholarship from the China Scholarship Council. The authors gratefully acknowledge the support of the TUM’s Thematic Graduate Center / Faculty Graduate Center Medical Life Science and Technology at Technische Universität München