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The effect of combination therapy on critical-size bone defects using non-activated platelet-rich plasma and adipose-derived stem cells

  • Woonhyeok Jeong
  • Young Seok Kim
  • Tai Suk Roh
  • Eun Hye Kang
  • Bok Ki Jung
  • In Sik YunEmail author
Original Article

Abstract

Purpose

Non-activated platelet-rich plasma (nPRP) slowly releases growth factors that induce bone regeneration. Adipose tissue-derived stem cells (ASCs) are also known to induce osteoblast differentiation. In this study, we investigated the combined effect of nPRP and ASC treatment compared with single therapy on bone regeneration.

Methods

Thirty New Zealand white rabbits with 15 × 15 mm2 calvarial defects were randomly divided into four treatment groups: control, nPRP, ASC, or nPRP + ASC groups. For treatment, rabbits received a collagen sponge (Gelfoam®) saturated with 1 ml normal saline (controls), 1 ml non-activated PRP (nPRP group), 2 × 106 ASCs (ASCs group), or 2 × 106 ASCs plus l ml nPRP (nPRP + ASCs group). After 16 weeks, bone volume and new bone surface area were measured, using three-dimensional computed tomography and digital photography. Bone regeneration was also histologically analyzed.

Results

Bone surface area in the nPRP group was significantly higher than both the control and ASC groups (p < 0.001 and p < 0.01, respectively). The percentage of regenerated bone surface area in the nPRP + ASC group was also significantly higher than the corresponding ratios in the control group (p < 0.001). The volume of new bone in the nPRP group was increased compared to the controls (p < 0.05).

Conclusion

Our results demonstrate that slow-releasing growth factors from nPRP did not influence ASC activation in this model of bone healing. PRP activation is important for the success of combination therapy using nPRP and ASCs.

Keywords

Mesenchymal stem cells Platelet-rich plasma Osteogenesis Skull 

Notes

Funding

This study was funded by the National Research Foundation of Korea (NRF) funded by the Korean government (No. NRF-2018R1D1A1B07042537).

Compliance with ethical standards

All procedures performed in studies involving animals were in accordance with the ethical standards of the Yonsei University Animal Care and Experiment Committee (2013–0408).

Conflicts of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Rawashdeh MA, Telfah H (2008) Secondary alveolar bone grafting: the dilemma of donor site selection and morbidity. Br J Oral Maxillofac Surg 46:665–670CrossRefGoogle Scholar
  2. 2.
    Friedenstein AJ, Petrakova KV, Kurolesova AI, Frolova GP (1968) Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation 6:230–247CrossRefGoogle Scholar
  3. 3.
    Mendez-Ferrer S, Michurina TV, Ferraro F et al (2010) Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature 466:829–834CrossRefGoogle Scholar
  4. 4.
    Chu W, Gan Y, Zhuang Y, Wang X, Zhao J, Tang T, Dai K (2018) Mesenchymal stem cells and porous beta-tricalcium phosphate composites prepared through stem cell screen-enrich-combine(-biomaterials) circulating system for the repair of critical size bone defects in goat tibia. Stem Cell Res Ther 9:157CrossRefGoogle Scholar
  5. 5.
    Zuk PA, Zhu M, Ashjian P, de Ugarte DA, Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P, Hedrick MH (2002) Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 13:4279–4295CrossRefGoogle Scholar
  6. 6.
    De Francesco F, Ricci G, D'Andrea F et al (2015) Human adipose stem cells: from bench to bedside. Tissue Eng Part B Rev 21:572–584CrossRefGoogle Scholar
  7. 7.
    Mesimaki K, Lindroos B, Tornwall J et al (2009) Novel maxillary reconstruction with ectopic bone formation by GMP adipose stem cells. Int J Oral Maxillofac Surg 38:201–209CrossRefGoogle Scholar
  8. 8.
    Ruetze M, Richter W (2014) Adipose-derived stromal cells for osteoarticular repair: trophic function versus stem cell activity. Expert Rev Mol Med 16:e9CrossRefGoogle Scholar
  9. 9.
    Brocher J, Janicki P, Voltz P, Seebach E, Neumann E, Mueller-Ladner U, Richter W (2013) Inferior ectopic bone formation of mesenchymal stromal cells from adipose tissue compared to bone marrow: rescue by chondrogenic pre-induction. Stem Cell Res 11:1393–1406CrossRefGoogle Scholar
  10. 10.
    Smith SE, Roukis TS (2009) Bone and wound healing augmentation with platelet-rich plasma. Clin Podiatr Med Surg 26:559–588CrossRefGoogle Scholar
  11. 11.
    Scherer SS, Tobalem M, Vigato E et al (2012) Nonactivated versus thrombin-activated platelets on wound healing and fibroblast-to-myofibroblast differentiation in vivo and in vitro. Plast Reconstr Surg 129:46e–54eCrossRefGoogle Scholar
  12. 12.
    Dodde R 2nd, Yavuzer R, Bier UC et al (2000) Spontaneous bone healing in the rabbit. J Craniofac Surg 11:346–349CrossRefGoogle Scholar
  13. 13.
    Im GI, Shin YW, Lee KB (2005) Do adipose tissue-derived mesenchymal stem cells have the same osteogenic and chondrogenic potential as bone marrow-derived cells? Osteoarthr Cartil 13:845–853CrossRefGoogle Scholar
  14. 14.
    Grayson WL, Bunnell BA, Martin E, Frazier T, Hung BP, Gimble JM (2015) Stromal cells and stem cells in clinical bone regeneration. Nat Rev Endocrinol 11:140–150CrossRefGoogle Scholar
  15. 15.
    De Ugarte DA, Morizono K, Elbarbary A et al (2003) Comparison of multi-lineage cells from human adipose tissue and bone marrow. Cells Tissues Organs 174:101–109CrossRefGoogle Scholar
  16. 16.
    Hattori H, Masuoka K, Sato M et al (2006) Bone formation using human adipose tissue-derived stromal cells and a biodegradable scaffold. J Biomed Mater Res B Appl Biomater 76:230–239CrossRefGoogle Scholar
  17. 17.
    Yang M, Ma QJ, Dang GT, Ma KT, Chen P, Zhou CY (2005) In vitro and in vivo induction of bone formation based on ex vivo gene therapy using rat adipose-derived adult stem cells expressing BMP-7. Cytotherapy 7:273–281CrossRefGoogle Scholar
  18. 18.
    Hao W, Hu YY, Wei YY, Pang L, Lv R, Bai JP, Xiong Z, Jiang M (2008) Collagen I gel can facilitate homogenous bone formation of adipose-derived stem cells in PLGA-beta-TCP scaffold. Cells Tissues Organs 187:89–102CrossRefGoogle Scholar
  19. 19.
    Pacifici L, Casella F, Maggiore C (2002) Platelet rich plasma (PRP): potentialities and techniques of extraction. Minerva Stomatol 51:341–350Google Scholar
  20. 20.
    Wen YH, Lin WY, Lin CJ, Sun YC, Chang PY, Wang HY, Lu JJ, Yeh WL, Chiueh TS (2018) Sustained or higher levels of growth factors in platelet-rich plasma during 7-day storage. Clin Chim Acta 483:89–93CrossRefGoogle Scholar
  21. 21.
    Casati L, Celotti F, Negri-Cesi P, Sacchi MC, Castano P, Colciago A (2014) Platelet derived growth factor (PDGF) contained in platelet rich plasma (PRP) stimulates migration of osteoblasts by reorganizing actin cytoskeleton. Cell Adhes Migr 8:595–602CrossRefGoogle Scholar
  22. 22.
    Tajima S, Tobita M, Orbay H, Hyakusoku H, Mizuno H (2015) Direct and indirect effects of a combination of adipose-derived stem cells and platelet-rich plasma on bone regeneration. Tissue Eng A 21:895–905CrossRefGoogle Scholar
  23. 23.
    Senarath-Yapa K, McArdle A, Renda A, Longaker M, Quarto N (2014) Adipose-derived stem cells: a review of signaling networks governing cell fate and regenerative potential in the context of craniofacial and long bone skeletal repair. Int J Mol Sci 15:9314–9330CrossRefGoogle Scholar
  24. 24.
    Cvetkovic VJ, Najdanovic JG, Vukelic-Nikolic MD et al (2015) Osteogenic potential of in vitro osteo-induced adipose-derived mesenchymal stem cells combined with platelet-rich plasma in an ectopic model. Int Orthop 39:2173–2180CrossRefGoogle Scholar
  25. 25.
    Man Y, Wang P, Guo Y, Xiang L, Yang Y, Qu Y, Gong P, Deng L (2012) Angiogenic and osteogenic potential of platelet-rich plasma and adipose-derived stem cell laden alginate microspheres. Biomaterials 33:8802–8811CrossRefGoogle Scholar
  26. 26.
    Marx RE (2001) Platelet-rich plasma (PRP): what is PRP and what is not PRP? Implant Dent 10:225–228CrossRefGoogle Scholar
  27. 27.
    Bruder SP, Jaiswal N, Haynesworth SE (1997) Growth kinetics, self-renewal, and the osteogenic potential of purified human mesenchymal stem cells during extensive subcultivation and following cryopreservation. J Cell Biochem 64:278–294CrossRefGoogle Scholar
  28. 28.
    Kim MH, Woo SK, Lee KC, An GI, Pandya D, Park NW, Nahm SS, Eom KD, Kim KI, Lee TS, Kim CW, Kang JH, Yoo J, Lee YJ (2015) Longitudinal monitoring adipose-derived stem cell survival by PET imaging hexadecyl-4-(1)(2)(4)I-iodobenzoate in rat myocardial infarction model. Biochem Biophys Res Commun 456:13–19CrossRefGoogle Scholar
  29. 29.
    Quach CH, Jung KH, Paik JY et al (2012) Quantification of early adipose-derived stem cell survival: comparison between sodium iodide symporter and enhanced green fluorescence protein imaging. Nucl Med Biol 39:1251–1260CrossRefGoogle Scholar
  30. 30.
    Jeon YR, Jung BK, Roh TS, Kang EH, Lee WJ, Rah DK, Lew DH, Yun IS (2016) Comparing the effect of nonactivated platelet-rich plasma, activated platelet-rich plasma, and bone morphogenetic protein-2 on calvarial bone regeneration. J Craniofac Surg 27:317–321CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Woonhyeok Jeong
    • 1
  • Young Seok Kim
    • 2
  • Tai Suk Roh
    • 2
  • Eun Hye Kang
    • 3
  • Bok Ki Jung
    • 2
  • In Sik Yun
    • 2
    Email author
  1. 1.Department of Plastic and Reconstructive Surgery, Keimyung University School of MedicineDongsan Medical CenterDaeguSouth Korea
  2. 2.Department of Plastic and Reconstructive Surgery, Institute for Human Tissue RestorationYonsei University Health System, Gangnam Severance HospitalSeoulSouth Korea
  3. 3.Department of Plastic and Reconstructive Surgery, Institute for Human Tissue RestorationYonsei University Health System, Severance HospitalSeoulSouth Korea

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