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Platelet-Derived Growth Factor-BB Priming Enhances Vasculogenic Capacity of Bone Marrow-Derived Endothelial Precursor Like Cells

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Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Background:

Human endothelial progenitor cells (EPCs) were first identified in the peripheral blood and later in the cord blood and bone marrow (BM) with different vascularization capacity and different surface marker profiles. However, their identity and functional roles in neovascularization have not been clearly demonstrated in vivo and in vitro.

Methods:

Characterization of BM-EPC like cells were performed by fluorescence-activated cell sorting, immunofluorescence staining, enzyme-linked immunosorbent assay, Matrigel tube formation assay, and western blot analysis.

Results:

BM-EPC like cells were identified by selective adhesion to fibronectin and collagen from BM mononuclear cells, which generate fast-growing colonies with spindle morphology, express surface markers of CD105, vWF, UEA-I lectin binding, secrete HGF, VEGF, TGF-beta1 but can be distinguished from circulating EPC and endothelial cells by no expression of surface markers such as CD31, CD309, CD45, and CD34. These BM-EPC like cells shared many cell surface markers of BM-mesenchymal stem cells (MSC) but also can be distinguished by their vasculogenic property and other unique surface markers. Furthermore, the vasculogenic capacity of BM-EPC like cells were enhanced by co-culture of BM-MSC or PDGF-BB priming. PDGF-BB stimulated cell migration, proliferation, and secretion of laminin β-1, which was proposed as one of the mechanisms involved in the better vascularization of BM-EPC like cells.

Conclusion

PDGF-BB priming may be applied to improve the potency and function of BM-EPC like cells as vasculogenic cell therapy for the ischemic vascular repair.

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References

  1. Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997;275:964–6.

    Article  CAS  PubMed  Google Scholar 

  2. Keighron C, Lyons CJ, Creane M, O’Brien T, Liew A. Recent advances in endothelial progenitor cells toward their use in clinical translation. Front Med. 2018;5:354.

    Article  Google Scholar 

  3. Haider KH, Salim A, Al-Reshidi MA. Endothelial progenitor cells for cellular angiogenesis and repair: lessons learned from experimental animal models. Regen Med. 2017;12:969–82.

    Article  CAS  PubMed  Google Scholar 

  4. Patry C, Stamm D, Betzen C, Tönshoff B, Yard BA, Beck GC, et al. CXCR-4 expression by circulating endothelial progenitor cells and SDF-1 serum levels are elevated in septic patients. J Inflamm (Lond). 2018;15:10.

    Article  Google Scholar 

  5. Li L, Liu H, Xu C, Deng M, Song M, Yu X, et al. VEGF promotes endothelial progenitor cell differentiation and vascular repair through connexin 43. Stem Cell Res Ther. 2017;8:237.

    Article  Google Scholar 

  6. Maeng YS, Choi HJ, Kwon JY, Park YW, Choi KS, Min JK, et al. Endothelial progenitor cell homing: prominent role of the IGF2-IGF2R-PLCβ2 axis. Blood. 2009;113:233–43.

    CAS  Google Scholar 

  7. Di Santo S, Yang Z, Wyler von Ballmoos M, Voelzmann J, Diehm N, Baumgartner I, et al. Novel cell-free strategy for therapeutic angiogenesis: in vitro generated conditioned medium can replace progenitor cell transplantation. PloS One 2019;4:e5643.

  8. Wang T, Fang X, Yin ZS. Endothelial progenitor cell-conditioned medium promotes angiogenesis and is neuroprotective after spinal cord injury. Neural Regen Res. 2018;13:887.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Kaushik K, Das A. Endothelial progenitor cell therapy for chronic wound tissue regeneration. Cytotherapy. 2019;21:1137–50.

    Article  CAS  PubMed  Google Scholar 

  10. Maki T, Morancho A, Martinez-San Segundo P, Hayakawa K, Takase H, Liang AC, et al. Endothelial progenitor cell secretome and oligovascular repair in a mouse model of prolonged cerebral hypoperfusion. Stroke. 2018;49:1003–10.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Zhang R, Yang J, Yuan J, Song B, Wang Y, Xu Y. The therapeutic value of bone marrow-derived endothelial progenitor cell transplantation after intracerebral hemorrhage in rats. Front Neurol. 2017;8:174.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Wils J, Favre J, Bellien J. Modulating putative endothelial progenitor cells for the treatment of endothelial dysfunction and cardiovascular complications in diabetes. Pharmacol Ther. 2017;170:98–115.

    Article  CAS  PubMed  Google Scholar 

  13. Berezin AE. The endothelial progenitor cell dysfunction in hypertension: the diagnostic and predictive values. Vessel Plus. 2018;2:22.

    Article  Google Scholar 

  14. Williamson K, Stringer SE, Alexander MY. Endothelial progenitor cells enter the aging arena. Front Physiol. 2012;3:30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Bauersachs J, Widder JD. Endothelial dysfunction in heart failure. Pharmacol Rep. 2008;60:119.

    CAS  PubMed  Google Scholar 

  16. Li CS, Neu MB, Shaw LC, Grant MB. Endothelial progenitor dysfunction in the pathogenesis of diabetic retinopathy: treatment concept to correct diabetes-associated deficits. EPMA Journal. 2010;1:88–100.

    Article  Google Scholar 

  17. Teraa M, Sprengers RW, Westerweel PE, Gremmels H, Goumans MJT, Teerlink T, et al. Bone marrow alterations and lower endothelial progenitor cell numbers in critical limb ischemia patients. PLoS One. 2013;8:e55592.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Domingues A, Bujko K, Kucia M, Ratajczak J, Ratajczak MZ. Efficient ex vivo expansion of highly purified human umbilical cord blood-derived very small CD34+ lin-CD45-stem cells into functional endothelial cells in vitro in chemically identified, feeder layer-free medium supplemented with nicotinamide. Blood. 2019;134:4882.

    Article  Google Scholar 

  19. Shen WC, Chou YH, Huang HP, Sheen JF, Hung SC, Chen HF. Induced pluripotent stem cell-derived endothelial progenitor cells attenuate ischemic acute kidney injury and cardiac dysfunction. Stem Cell Res Ther. 2018;9:344.

    Article  Google Scholar 

  20. Lu H, Mei H, Wang F, Zhao Q, Wang S, Liu L, et al. Decreased phosphorylation of PDGFR-β impairs the angiogenic potential of expanded endothelial progenitor cells via the inhibition of PI3K/Akt signaling. Int J Mol Med. 2017;39:1492–504.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Bhatwadekar AD, Shaw LC, Grant MB. Promise of endothelial progenitor cell for treatment of diabetic retinopathy. Expert Rev Endocrinol Metab. 2010;5:29–37.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Amini AR, Laurencin CT, Nukavarapu SP. Differential analysis of peripheral blood-and bone marrow-derived endothelial progenitor cells for enhanced vascularization in bone tissue engineering. J Orthop Res. 2012;30:1507–15.

    Article  CAS  PubMed  Google Scholar 

  23. Fang J, Guo Y, Tan S, Li Z, Xie H, Chen P, et al. Autologous endothelial progenitor cells transplantation for acute ischemic stroke: a 4-year follow-up study. Stem Cells Transl Med. 2019;8:14–21.

    Article  CAS  PubMed  Google Scholar 

  24. Andrae J, Gallini R, Betsholtz C. Role of platelet-derived growth factors in physiology and medicine. Genes Dev. 2008;22:1276–312.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Evrova O, Buschmann J. In vitro and in vivo effects of PDGF-BB delivery strategies on tendon healing: a review. Eur Cell Mater. 2017;34:15–39.

    Article  CAS  PubMed  Google Scholar 

  26. Xiang DN, Feng YF, Wang J, Zhang X, Shen JJ, Zou R, et al. Platelet-derived growth factor-BB promotes proliferation and migration of retinal microvascular pericytes by up-regulating the expression of C-X-C chemokine receptor types 4. Exp Ther Med. 2019;18:4022–30.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Liang T, Zhu L, Gao W, Gong M, Ren J, Yao H, et al. Coculture of endothelial progenitor cells and mesenchymal stem cells enhanced their proliferation and angiogenesis through PDGF and Notch signaling. FEBS Open Bio. 2017;7:1722–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Kemp SS, Aguera KN, Cha B, Davis GE. Defining endothelial cell-derived factors that promote pericyte recruitment and capillary network assembly. Arterioscler Thromb Vasc Biol. 2020;40:2632–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Fang J, Huang X, Han X, Zheng Z, Hu C, Chen T, et al. Endothelial progenitor cells promote viability and nerve regenerative ability of mesenchymal stem cells through PDGF-BB/PDGFR-β signaling. Aging. 2020;12:106.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Rolny C, Nilsson I, Magnusson P, Armulik A, Jakobsson L, Wentzel P, et al. Platelet-derived growth factor receptor-β promotes early endothelial cell differentiation. Blood. 2006;108:1877–86.

    Article  CAS  PubMed  Google Scholar 

  31. Wang H, Yin YG, Huang H, Zhao XH, Yu J, Wang Q, et al. Transplantation of EPCs overexpressing PDGFR-β promotes vascular repair in the early phase after vascular injury. BMC Cardiovasc Disord. 2016;16:179.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Spigoni V, Picconi A, Cito M, Ridolfi V, Bonomini S, Casali C, et al. Pioglitazone improves in vitro viability and function of endothelial progenitor cells from individuals with impaired glucose tolerance. PLoS One. 2012;7:e48283.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Piao J, Park JS, Hwang DY, Hong HS, Son Y. Substance P blocks β-aminopropionitrile-induced aortic injury through modulation of M2 monocyte-skewed monocytopoiesis. Transl Res. 2021;228:76–93.

    Article  CAS  PubMed  Google Scholar 

  34. Zhang M, Ahn W, Kim S, Hong HS, Quan C, Son Y. Endothelial precursor cells stimulate pericyte-like coverage of bone marrow-derived mesenchymal stem cells through platelet-derived growth factor-BB induction, which is enhanced by substance P. Microcirculation. 2017;24:e12394.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Kawada K, Upadhyay G, Ferandon S, Janarthanan S, Hall M, Vilardaga JP, et al. Cell migration is regulated by platelet-derived growth factor receptor endocytosis. Mol Cell Biol. 2009;29:4508–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by Korean Health Technology R&D Project grant, Grant/Award Number: (HI18C1492), the Technology Innovation Program (1415179737,20018551) funded By the Ministry of Trade, Industry & Energy (MOTIE, Korea), and the Korean Fund for Regenerative Medicine(KFRM) grant funded by the Korea government (the Ministry of Science and ICT, the Ministry of Health & Welfare), (23C0110L1).

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Author notes

  1. Do Young Kim and Gabee Park have been contributed equally to this work.

Authors and Affiliations

  1. Department of Genetic Engineering, College of Life Science and Graduate School of Biotechnology, Kyung Hee University, Yongin, 17104, South Korea

    Do Young Kim, Gabee Park, Suna Kim & Youngsook Son

  2. Department of Biomedical Science and Technology, Graduated School, Kyung Hee University, Seoul, Korea

    Do Young Kim, Hyun Sook Hong & Youngsook Son

  3. KHU Institute of Regenerative Medicine, KHU Hospital, Seoul, Korea

    Hyun Sook Hong & Youngsook Son

  4. Elphis Cell Therapeutics Inc, Yongin, Korea

    Gabee Park & Youngsook Son

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  1. Do Young Kim
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Correspondence to Youngsook Son.

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Kim, D.Y., Park, G., Hong, H.S. et al. Platelet-Derived Growth Factor-BB Priming Enhances Vasculogenic Capacity of Bone Marrow-Derived Endothelial Precursor Like Cells. Tissue Eng Regen Med 20, 695–704 (2023). https://doi.org/10.1007/s13770-023-00546-9

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