Cellular and Molecular Life Sciences

, Volume 75, Issue 3, pp 547–561 | Cite as

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

  • Shan Wang
  • Miaohua Mo
  • Jinmei Wang
  • Sobia Sadia
  • Bihua Shi
  • Xiaobing Fu
  • Lin Yu
  • Edward E. Tredget
  • Yaojiong Wu
Original Article
  • 271 Downloads

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.

Keywords

Mesenchymal stem cells Subpopulation PDGFR-β (CD140b) Angiogenesis Wound healing 

Notes

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).

Author 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.

Compliance with ethical standards

Conflict of interest

The authors report no conflicts of interest.

Supplementary material

18_2017_2641_MOESM1_ESM.docx (15 kb)
Supplementary material 1 (DOCX 15 kb)

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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Shan Wang
    • 1
    • 2
  • Miaohua Mo
    • 1
    • 2
  • Jinmei Wang
    • 2
  • Sobia Sadia
    • 1
    • 2
  • Bihua Shi
    • 3
  • Xiaobing Fu
    • 4
    • 5
  • Lin Yu
    • 6
  • Edward E. Tredget
    • 7
  • Yaojiong Wu
    • 2
    • 3
  1. 1.School of Life SciencesTsinghua UniversityBeijingChina
  2. 2.The Shenzhen Key Laboratory of Health Sciences and Technology, Graduate School at ShenzhenTsinghua UniversityShenzhenChina
  3. 3.Tsinghua-Berkeley Shenzhen Institute (TBSI)Tsinghua UniversityShenzhenChina
  4. 4.Wound Healing and Cell Biology LaboratoryInstitute of Basic Medical Science, Chinese PLA General HospitalBeijingChina
  5. 5.Stem Cell and Tissue Regeneration LaboratoryThe First Affiliated Hospital, General Hospital of PLABeijingChina
  6. 6.Peking University Shenzhen Hospital, Shenzhen Key Laboratory of Gynecological Diagnostic Technology ResearchShenzhenChina
  7. 7.Wound Healing Research Group, Department of SurgeryUniversity of AlbertaEdmontonCanada

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