Abstract
Mesenchymal stem cells (MSCs) are heterogeneous likely consisting of subpopulations with various therapeutic potentials. Here we attempted to acquire a subset of MSCs with enhanced effect in wound healing. We found that human placental MSCs expressing platelet-derived growth factor (PDGF) receptor (PDGFR)-β exhibited greater proliferation rates and generated more colony-forming unit-fibroblast (CFU-F), compared to PDGFR-β(-) MSCs. Notably, PDGFR-β(+) MSCs expressed higher levels of pro-angiogenic factors such as Ang1, Ang2, VEGF, bFGF and PDGF. When 10(6) GFP-expressing MSCs were topically applied into excisional wounds in mice, PDGFR-β(+) MSCs actively incorporated into the wound tissue, resulting in enhanced engraftment (3.92 ± 0.31 × 10(5) remained in wound by 7 days) and accelerated wound closure; meanwhile, PDGFR-β(-) MSCs tended to remain on the top of the wound bed with significantly fewer cells (2.46 ± 0.26 × 10(5)) engrafted into the wound, suggesting enhanced chemotactic migration and engraftment of PDGFR-β(+) MSCs into the wound. Real-Time PCR and immunostain analyses revealed that the expression of PDGF-B was upregulated after wounding; transwell migration assay showed that PDGFR-β(+) MSCs migrated eightfold more than PDGFR-β(-) MSCs toward PDGF-BB. Intriguingly, PDGFR-β(+) MSC-treated wounds showed significantly enhanced angiogenesis compared to PDGFR-β(-) MSC- or vehicle-treated wounds. Thus, our results indicate that PDGFR-β identifies a subset of MSCs with enhanced chemotactic migration to wound injury and effect in promoting angiogenesis and wound healing, implying a greater therapeutic potential for certain diseases.