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Platelet-derived growth factor receptor beta identifies mesenchymal stem cells with enhanced engraftment to tissue injury and pro-angiogenic property

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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 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.

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Acknowledgements

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).

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Author notes

  1. Shan Wang and Miaohua Mo contributed equally to this work.

Authors and Affiliations

  1. School of Life Sciences, Tsinghua University, Beijing, China

    Shan Wang, Miaohua Mo & Sobia Sadia

  2. The Shenzhen Key Laboratory of Health Sciences and Technology, Graduate School at Shenzhen, Tsinghua University, L406A, Tsinghua Campus, The University Town, Shenzhen, 518055, China

    Shan Wang, Miaohua Mo, Jinmei Wang, Sobia Sadia & Yaojiong Wu

  3. Tsinghua-Berkeley Shenzhen Institute (TBSI), Tsinghua University, Shenzhen, China

    Bihua Shi & Yaojiong Wu

  4. Wound Healing and Cell Biology Laboratory, Institute of Basic Medical Science, Chinese PLA General Hospital, Beijing, China

    Xiaobing Fu

  5. Stem Cell and Tissue Regeneration Laboratory, The First Affiliated Hospital, General Hospital of PLA, Beijing, China

    Xiaobing Fu

  6. Peking University Shenzhen Hospital, Shenzhen Key Laboratory of Gynecological Diagnostic Technology Research, Shenzhen, China

    Lin Yu

  7. Wound Healing Research Group, Department of Surgery, University of Alberta, Edmonton, AB, Canada

    Edward E. Tredget

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  1. Shan Wang
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Contributions

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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Correspondence to Yaojiong Wu.

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Wang, S., Mo, M., Wang, J. et al. Platelet-derived growth factor receptor beta identifies mesenchymal stem cells with enhanced engraftment to tissue injury and pro-angiogenic property. Cell. Mol. Life Sci. 75, 547–561 (2018). https://doi.org/10.1007/s00018-017-2641-7

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