Skip to main content

Advertisement

Log in

Activation of cell adhesion and migration is an early event of platelet-rich plasma (PRP)-dependent stimulation of human adipose-derived stem/stromal cells

  • Research Article
  • Published:
Human Cell Aims and scope Submit manuscript

Abstract

Stem cell therapy is a promising treatment in regenerative medicine. Human adipose-derived stem/stromal cells (hASCs), a type of mesenchymal stem cell, are easy to harvest. In plastic and aesthetic surgery, hASC may be applied in the treatment of fat grafting, wound healing, and scar remodeling. Platelet-rich plasma (PRP) contains various growth factors, including platelet-derived growth factor (PDGF), which accelerates wound healing. We previously reported that PRP promotes the proliferation of hASC via multiple signaling pathways, and we evaluated the effect of PRP on the stimulation of hASC adhesion and migration, leading to the proliferation of these cells. When hASCs were treated with PRP, AKT, ERK1/2, paxillin and RhoA were rapidly activated. PRP treatment led to the formation of F-actin stress fibers. Strong signals for integrin β1, paxillin and RhoA at the cell periphery of RPR-treated cells indicated focal adhesion. PRP promoted cell adhesion and movement of hASC, compared with the control group. Imatinib, an inhibitor of the PDGF receptor tyrosine kinase, inhibited the promotion of PRP-dependent cell migration. PDGF treatment of hASCs also stimulated cell adhesion and migration but to a lesser extent than PRP treatment. PRP promoted the adhesion and the migration of hASC, mediated by the activation of AKT in the integrin signaling pathway. PRP treatment was more effective than PDGF treatment in enhancing cell migration. Thus, the ability of PRPs to promote migration of hASC to enhance cell growth is evident.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Marquez-Curtis LA, Janowska-Wieczorek A, McGann LE, Elliott JA. Mesenchymal stromal cells derived from various tissues: Biological, clinical and cryopreservation aspects. Cryobiology. 2015;71:181–97.

    PubMed  CAS  Google Scholar 

  2. Koźlik M, Wójcicki P. The use of stem cells in plastic and reconstructive surgery. Adv Clin Exp Med. 2014;23:1011–7.

    PubMed  Google Scholar 

  3. Kim YJ, Jeong JH. Clinical application of adipose stem cells in plastic surgery. J Korean Med Sci. 2014;29:462–7.

    PubMed  PubMed Central  CAS  Google Scholar 

  4. Torres FC, Rodrigues CJ, Stocchero IN, Ferreira MC. Stem cells from the fat tissue of rabbits: an easy-to-find experimental source. Aesthetic Plast Surg. 2007;31:574–8.

    PubMed  Google Scholar 

  5. Zhang M, Zhang P, Liu Y, Zhou Y. GSK3 inhibitor AR-A014418 promotes osteogenic differentiation of human adipose-derived stem cells via ERK and mTORC2/Akt signaling pathway. Biochem Biophys Res Commun. 2017;490:182–8.

    PubMed  CAS  Google Scholar 

  6. Galeano-Garces C, Camilleri ET, Riester SM, et al. Molecular validation of chondrogenic differentiation and hypoxia responsiveness of platelet-lysate expanded adipose tissue-derived human mesenchymal stromal cells. Cartilage. 2017;8:283–99.

    PubMed  CAS  Google Scholar 

  7. Paul NE, Denecke B, Kim BS, Dreser A, Bernhagen J, Pallua N. The effect of mechanical stress on the proliferation, adipogenic differentiation and gene expression of human adipose-derived stem cells. J Tissue Eng Regen Med. 2018;12:276–84.

    PubMed  CAS  Google Scholar 

  8. Jahromi M, Razavi S, Amirpour N, Khosravizadeh Z. Paroxetine can enhance neurogenesis during neurogenic differentiation of human adipose-derived stem cells. Avicenna J Med Biotechnol. 2016;8:152–8.

    PubMed  PubMed Central  Google Scholar 

  9. Gaur M, Dobke M, Lunyak VV. Mesenchymal stem cells from adipose tissue in clinical applications for dermatological indications and skin aging. Int J Mol Sci. 2017;18:201.

    Google Scholar 

  10. Takahashi H, Ishikawa H, Tanaka A. Regenerative medicine for Parkinson’s disease using differentiated nerve cells derived from human buccal fat pad stem cells. Hum Cell. 2017;30:60–71.

    PubMed  CAS  Google Scholar 

  11. Gentile P, Sterodimas A, Pizzicannella J, et al. Systematic review: allogenic use of stromal vascular fraction (SVF) and decellularized extracellular matrices (ECM) as advanced therapy medicinal products (ATMP) in tissue regeneration. Int J Mol Sci. 2020;21:4982.

    PubMed  PubMed Central  CAS  Google Scholar 

  12. Liu TM. Application of mesenchymal stem cells derived from human pluripotent stem cells in regenerative medicine. World J Stem Cells. 2021;13:1826–44.

    PubMed  PubMed Central  Google Scholar 

  13. Geissler PJ, Davis K, Roostaeian J, Unger J, Huang J, Rohrich RJ. Improving fat transfer viability: the role of aging, body mass index, and harvest site. Plast Reconstr Surg. 2014;134:227–32.

    PubMed  CAS  Google Scholar 

  14. van Harmelen V, Skurk T, Röhrig K, et al. Effect of BMI and age on adipose tissue cellularity and differentiation capacity in women. Int J Obes Relat Metab Disord. 2003;27:889–95.

    PubMed  Google Scholar 

  15. Tobita M, Tajima S, Mizuno H. Adipose tissue-derived mesenchymal stem cells and platelet-rich plasma: stem cell transplantation methods that enhance stemness. Stem Cell Res Ther. 2015;6:215.

    PubMed  PubMed Central  Google Scholar 

  16. van Tienen FH, van der Kallen CJ, Lindsey PJ, Wanders RJ, van Greevenbroek MM, Smeets HJ. Preadipocytes of type 2 diabetes subjects display an intrinsic gene expression profile of decreased differentiation capacity. Int J Obes. 2011;35:1154–64.

    Google Scholar 

  17. Poglio S, Galvani S, Bour S, et al. Adipose tissue sensitivity to radiation exposure. Am J Pathol. 2009;174:44–53.

    PubMed  PubMed Central  CAS  Google Scholar 

  18. Eppley BL, Woodell JE, Higgins J. Platelet quantification and growth factor analysis from platelet-rich plasma: implications for wound healing. Plast Reconstr Surg. 2004;114:1502–8.

    PubMed  Google Scholar 

  19. Eppley BL, Pietrzak WS, Blanton M. Platelet-rich plasma: a review of biology and applications in plastic surgery. Plast Reconstr Surg. 2006;118:147e-e159.

    PubMed  CAS  Google Scholar 

  20. Dohan Ehrenfest DM, Andia I, Zumstein MA, Zhang CQ, Pinto NR, Bielecki T. Classification of platelet concentrates (Platelet-Rich Plasma-PRP, Platelet-Rich Fibrin-PRF) for topical and infiltrative use in orthopedic and sports medicine: current consensus, clinical implications and perspectives. Muscles Ligaments Tendons J. 2014;4:3–9.

    PubMed  PubMed Central  Google Scholar 

  21. Lubkowska A, Dolegowska B, Banfi G. Growth factor content in PRP and their applicability in medicine. J Biol Regul Homeost Agents. 2012;26:3s–22s.

    PubMed  CAS  Google Scholar 

  22. Heldin CH, Lennartsson J. Structural and functional properties of platelet-derived growth factor and stem cell factor receptors. Cold Spring Harb Perspect Biol. 2013;5: a009100.

    PubMed  PubMed Central  Google Scholar 

  23. Kang YJ, Jeon ES, Song HY, et al. Role of c-Jun N-terminal kinase in the PDGF-induced proliferation and migration of human adipose tissue-derived mesenchymal stem cells. J Cell Biochem. 2005;95:1135–45.

    PubMed  CAS  Google Scholar 

  24. Kim JH, Park SG, Song SY, Kim JK, Sung JH. Reactive oxygen species-responsive miR-210 regulates proliferation and migration of adipose-derived stem cells via PTPN2. Cell Death Dis. 2013;4: e588.

    PubMed  PubMed Central  CAS  Google Scholar 

  25. Kakudo N, Minakata T, Mitsui T, Kushida S, Notodihardjo FZ, Kusumoto K. Proliferation-promoting effect of platelet-rich plasma on human adipose-derived stem cells and human dermal fibroblasts. Plast Reconstr Surg. 2008;122:1352–60.

    PubMed  CAS  Google Scholar 

  26. Hara T, Kakudo N, Morimoto N, Ogawa T, Lai F, Kusumoto K. Platelet-rich plasma stimulates human dermal fibroblast proliferation via a Ras-dependent extracellular signal-regulated kinase 1/2 pathway. J Artif Organs. 2016;19:372–7.

    PubMed  CAS  Google Scholar 

  27. Lai F, Kakudo N, Morimoto N, et al. Platelet-rich plasma enhances the proliferation of human adipose stem cells through multiple signaling pathways. Stem Cell Res Ther. 2018;9:107.

    PubMed  PubMed Central  CAS  Google Scholar 

  28. Lana JFSD, Purita J, Paulus C, et al. Contributions for classification of platelet rich plasma-proposal of a new classification: MARSPILL. Regen Med. 2017;12:565–74.

    PubMed  CAS  Google Scholar 

  29. Zuk PA, Zhu M, Ashjian P, et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell. 2002;13:4279–95.

    PubMed  PubMed Central  CAS  Google Scholar 

  30. Marques LF, Stessuk T, Camargo IC, Sabeh Junior N, dos Santos L, Ribeiro-Paes JT. Platelet-rich plasma (PRP): methodological aspects and clinical applications. Platelets. 2015;26:101–13.

    PubMed  CAS  Google Scholar 

  31. Aydin O, Karaca G, Pehlivanli F, et al. Platelet-rich plasma may offer a new hope in suppressed wound healing when compared to mesenchymal stem cells. J Clin Med. 2018;7:143.

    PubMed  PubMed Central  Google Scholar 

  32. Singer AJ, Clark RA. Cutaneous wound healing. N Engl J Med. 1999;341:738–46.

    PubMed  CAS  Google Scholar 

  33. Hye Kim J, Gyu Park S, Kim WK, Song SU, Sung JH. Functional regulation of adipose-derived stem cells by PDGF-D. Stem Cells. 2015;33:542–56.

    PubMed  Google Scholar 

  34. Baer PC, Schubert R, Bereiter-Hahn J, Plösser M, Geiger H. Expression of a functional epidermal growth factor receptor on human adipose-derived mesenchymal stem cells and its signaling mechanism. Eur J Cell Biol. 2009;88:273–83.

    PubMed  CAS  Google Scholar 

  35. Kakudo N, Shimotsuma A, Kusumoto K. Fibroblast growth factor-2 stimulates adipogenic differentiation of human adipose-derived stem cells. Biochem Biophys Res Commun. 2007;359:239–44.

    PubMed  CAS  Google Scholar 

  36. Ma Y, Kakudo N, Morimoto N, Lai F, Taketani S, Kusumoto K. Fibroblast growth factor-2 stimulates proliferation of human adipose-derived stem cells via Src activation. Stem Cell Res Ther. 2019;10:350.

    PubMed  PubMed Central  CAS  Google Scholar 

  37. Kakudo N, Kushida S, Suzuki K, et al. Effects of transforming growth factor-beta1 on cell motility, collagen gel contraction, myofibroblastic differentiation, and extracellular matrix expression of human adipose-derived stem cell. Hum Cell. 2012;25:87–95.

    PubMed  CAS  Google Scholar 

  38. Xu FT, Li HM, Yin QS, et al. Effect of activated autologous platelet-rich plasma on proliferation and osteogenic differentiation of human adipose-derived stem cells in vitro. Am J Transl Res. 2015;7:257–70.

    PubMed  PubMed Central  Google Scholar 

  39. Samberg M, Stone R 2nd, Natesan S, et al. Platelet rich plasma hydrogels promote in vitro and in vivo angiogenic potential of adipose-derived stem cells. Acta Biomater. 2019;87:76–87.

    PubMed  CAS  Google Scholar 

  40. Brown MC, Turner CE. Paxillin: adapting to change. Physiol Rev. 2004;84:1315–39.

    PubMed  CAS  Google Scholar 

  41. Huveneers S, Danen EH. Adhesion signaling - crosstalk between integrins. Src and Rho J Cell Sci. 2009;122:1059–69.

    PubMed  CAS  Google Scholar 

  42. Costa P, Scales TM, Ivaska J, Parsons M. Integrin-specific control of focal adhesion kinase and RhoA regulates membrane protrusion and invasion. PLoS ONE. 2013;8: e74659.

    PubMed  PubMed Central  CAS  Google Scholar 

  43. Ridley AJ, Paterson HF, Johnston CL, Diekmann D, Hall A. The small GTP-binding protein rac regulates growth factor-induced membrane ruffling. Cell. 1992;70:401–10.

    PubMed  CAS  Google Scholar 

  44. Ridley AJ, Hall A. The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors. Cell. 1992;70:389–99.

    PubMed  CAS  Google Scholar 

  45. McBeath R, Pirone DM, Nelson CM, Bhadriraju K, Chen CS. Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev Cell. 2004;6:483–95.

    PubMed  CAS  Google Scholar 

  46. Rolli-Derkinderen M, Toumaniantz G, Pacaud P, Loirand G. RhoA phosphorylation induces Rac1 release from guanine dissociation inhibitor alpha and stimulation of vascular smooth muscle cell migration. Mol Cell Biol. 2010;30:4786–96.

    PubMed  PubMed Central  CAS  Google Scholar 

  47. Goessler UR, Bugert P, Bieback K, et al. Integrin expression in stem cells from bone marrow and adipose tissue during chondrogenic differentiation. Int J Mol Med. 2008;21:271–9.

    PubMed  CAS  Google Scholar 

  48. Desgrosellier JS, Cheresh DA. Integrins in cancer: biological implications and therapeutic opportunities. Nat Rev Cancer. 2010;10:9–22.

    PubMed  PubMed Central  CAS  Google Scholar 

  49. Grose R, Hutter C, Bloch W, et al. A crucial role of beta 1 integrins for keratinocyte migration in vitro and during cutaneous wound repair. Development. 2002;129:2303–15.

    PubMed  CAS  Google Scholar 

  50. Wang Q, Zhang N, Hu L, Xi Y, Mi W, Ma Y. Integrin β1 in adipose-derived stem cells accelerates wound healing via activating PI3K/Akt pathway. Tissue Eng Regen Med. 2020;17:183–92.

    PubMed  PubMed Central  CAS  Google Scholar 

  51. Guneta V, Zhou Z, Tan NS, Sugii S, Wong MTC, Choong C. Recellularization of decellularized adipose tissue-derived stem cells: role of the cell-secreted extracellular matrix in cellular differentiation. Biomater Sci. 2017;6:168–78.

    PubMed  CAS  Google Scholar 

  52. Morandi EM, Verstappen R, Zwierzina ME, Geley S, Pierer G, Ploner C. ITGAV and ITGA5 diversely regulate proliferation and adipogenic differentiation of human adipose derived stem cells. Sci Rep. 2016;6:28889.

    PubMed  PubMed Central  CAS  Google Scholar 

  53. Yuan Z, Yan K, Wang J. Overexpression of integrin β(2) improves migration and engraftment of adipose-derived stem cells and augments angiogenesis in myocardial infarction. Ann Transl Med. 2022;10:863.

    PubMed  PubMed Central  CAS  Google Scholar 

  54. Mazini L, Rochette L, Admou B, Amal S, Malka G. Hopes and limits of adipose-derived stem cells (ADSCs) and mesenchymal stem cells (MSCs) in wound healing. Int J Mol Sci. 2020;21:1306.

    PubMed  PubMed Central  CAS  Google Scholar 

  55. Mahmoudian-Sani MR, Rafeei F, Amini R, Saidijam M. The effect of mesenchymal stem cells combined with platelet-rich plasma on skin wound healing. J Cosmet Dermatol. 2018;17:650–9.

    PubMed  Google Scholar 

  56. Ebrahim N, Dessouky AA, Mostafa O, et al. Adipose mesenchymal stem cells combined with platelet-rich plasma accelerate diabetic wound healing by modulating the Notch pathway. Stem Cell Res Ther. 2021;12:392.

    PubMed  PubMed Central  CAS  Google Scholar 

  57. Van Pham P, Bui KH, Ngo DQ, et al. Activated platelet-rich plasma improves adipose-derived stem cell transplantation efficiency in injured articular cartilage. Stem Cell Res Ther. 2013;4:91.

    PubMed  PubMed Central  Google Scholar 

  58. Gentile P, Garcovich S. Systematic review: adipose-derived mesenchymal stem cells, platelet-rich plasma and biomaterials as new regenerative strategies in chronic skin wounds and soft tissue defects. Int J Mol Sci. 2021;22:1538.

    PubMed  PubMed Central  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank Ms. Mie Aoki and members of the Central Research of Laboratory of Kansai Medical University for their technical assistances.

Funding

This study was supported by Grant-in-Aid for Scientific Research (C) No. 22K09898 from the Ministry of Education, Science, Sports, of Japan.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michika Fukui.

Ethics declarations

Competing interests

The authors declare that they have no competing interests.

Ethics approval and informed consent

The study was approved by the Ethics Review Board of Kansai Medical University in accordance under the ethical guidelines of the Helsinki Declaration of 1975. All specimens were collected and used with informed consent from the donors. Informed consent was written. The date range of recruitment was from April 2015 to March 2019.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file 1 (PDF 241 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fukui, M., Lai, F., Hihara, M. et al. Activation of cell adhesion and migration is an early event of platelet-rich plasma (PRP)-dependent stimulation of human adipose-derived stem/stromal cells. Human Cell 37, 181–192 (2024). https://doi.org/10.1007/s13577-023-00989-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13577-023-00989-1

Keywords

Navigation