Platelet-derived growth factor receptor beta identifies mesenchymal stem cells with enhanced engraftment to tissue injury and pro-angiogenic property
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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 106 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 × 105 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 × 105) 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.
KeywordsMesenchymal stem cells Subpopulation PDGFR-β (CD140b) Angiogenesis Wound healing
We gratefully thank Bing Yu for assistance in confocal analysis. This work was supported by grants from Natural Science Foundation of China (Nos. 31371404, 31571429), Natural Science Foundation of Guangdong (2015A030311041), and Shenzhen Science and Technology Innovation Committee (JCY20160301150838144).
SW: performed experiments and data analysis; SS, MM, JW, BS: performed experiments; LY: provided materials and designed experiments; XF, ET: designed experiments; YW: designed experiments and wrote the manuscript.
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Conflict of interest
The authors report no conflicts of interest.
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