Skip to main content
SpringerLink
Log in

Articular Cartilage Regeneration Utilizing Decellularized Human Placental Scaffold, Mesenchymal Stem Cells and Platelet Rich Plasma

  • Original Article
  • Published:
Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Background:

Articular cartilage repair has been a challenge in orthopedic practice due to the limited self-regenerative capability. Optimal treatment method for cartilage defects has not been defined. We investigated the effect of decellularized human placental (DHP) scaffold, mesenchymal stem cells (MSC) and platelet-rich plasma (PRP) on hyaline cartilage regeneration in a rat model.

Methods:

An osteochondral defect was created in trochlea region of the femur in all groups, bilaterally. No additional procedure was performed in control group (n = 14). Only the DHP scaffold was applied to the P group (n = 14). The DHP scaffold and 1 × 106 MSCs were applied to the PS group (n = 14). The DHP scaffold and PRP were applied to the PP group (n = 14). The DHP scaffold, 1 × 106 MSCs and PRP were applied to the PSP group (n = 14). Outcome measures at 12 weeks included Pineda histology score and qualitative histology.

Results:

The mean Pineda scores of P, PS, PP, and PSP groups were significantly better than the control group (p = 0.031, p = 0.002, p < 0.001, p < 0001, respectively). There was no statistically difference in mean Pineda scores of P, PS, PP, and PSP groups (p > 0.05).

Conclusion:

In conclusion, the DHP scaffold appears to be a promising scaffold on hyaline cartilage regeneration. The augmentation of DHP scaffold with MSCs and PRP combinations did not enhance its efficacy on articular cartilage regeneration.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

C: control, P: DHP scaffold, PS: DHP scaffold and MSCs, PP: DHP scaffold and PRP, PSP: DHP scaffold, MSCs and PRP

Similar content being viewed by others

References

  1. Lories RJ, Luyten FP. The bone-cartilage unit in osteoarthritis. Nat Rev Rheumatol. 2011;7:43–9.

    Article  CAS  PubMed  Google Scholar 

  2. Makris EA, Gomoll AH, Malizos KN, Hu JC, Athanasiou KA. Repair and tissue engineering techniques for articular cartilage. Nat Rev Rheumatol. 2015;11:21–34.

    Article  CAS  PubMed  Google Scholar 

  3. Lamplot JD, Schafer KA, Matava MJ. Treatment of failed articular cartilage reconstructive procedures of the knee: a systematic review. Orthop J Sports Med. 2018;6:2325967118761871.

    PubMed Central  PubMed  Google Scholar 

  4. O’Brien FJ. Biomaterials & scaffolds for tissue engineering. Mater Today (Kidlington). 2011;14:88–95.

    Article  Google Scholar 

  5. Ge Z, Li C, Heng BC, Cao G, Yang Z. Functional biomaterials for cartilage regeneration. J Biomed Mater Res A. 2012;100:2526–36.

    PubMed  Google Scholar 

  6. Spang MT, Christman KL. Extracellular matrix hydrogel therapies: In vivo applications and development. Acta Biomater. 2018;68:1–14.

    Article  CAS  PubMed  Google Scholar 

  7. Hoshiba T, Lu H, Kawazoe N, Chen G. Decellularized matrices for tissue engineering. Expert Opin Biol Ther. 2010;10:1717–28.

    Article  CAS  PubMed  Google Scholar 

  8. Leonel LCPC, Miranda CMFC, Coelho TM, Ferreira GAS, Caãada RR, Miglino MA, et al. Decellularization of placentas: establishing a protocol. Braz J Med Biol Res. 2017;51:e6382.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Francis MP, Breathwaite E, Bulysheva AA, Varghese F, Rodriguez RU, Dutta S, et al. Human placenta hydrogel reduces scarring in a rat model of cardiac ischemia and enhances cardiomyocyte and stem cell cultures. Acta Biomater. 2017;52:92–104.

    Article  CAS  PubMed  Google Scholar 

  10. Kakabadze Z, Kakabadze A, Chakhunashvili D, Karalashvili L, Berishvili E, Sharma Y, et al. Decellularized human placenta supports hepatic tissue and allows rescue in acute liver failure. Hepatology. 2018;67:1956–69.

    Article  CAS  PubMed  Google Scholar 

  11. Fisher JN, Tessaro I, Bertocco T, Peretti GM, Mangiavini L. The application of stem cells from different tissues to cartilage repair. Stem Cells Int. 2017;2017:2761678.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Niemeyer P, Szalay K, Luginbühl R, Südkamp NP, Kasten P. Transplantation of human mesenchymal stem cells in a non-autogenous setting for bone regeneration in a rabbit critical-size defect model. Acta Biomater. 2010;6:900–8.

    Article  CAS  PubMed  Google Scholar 

  13. Lin CC, Lin SC, Chiang CC, Chang MC, Lee OK. Reconstruction of bone defect combined with massive loss of periosteum using injectable human mesenchymal stem cells in biocompatible ceramic scaffolds in a porcine animal model. Stem Cells Int. 2019;2019:6832952.

    PubMed Central  PubMed  Google Scholar 

  14. Tatari H. The structure, physiology, and biomechanics of articular cartilage: injury and repair. Acta Orthop Traumatol Turc. 2007;41 Suppl 2:1–5.

    PubMed  Google Scholar 

  15. Goldring MB. Chondrogenesis, chondrocyte differentiation, and articular cartilage metabolism in health and osteoarthritis. Ther Adv Musculoskelet Dis. 2012;4:269–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Heijnen HF, Schiel AE, Fijnheer R, Geuze HJ, Sixma JJ. Activated platelets release two types of membrane vesicles: microvesicles by surface shedding and exosomes derived from exocytosis of multivesicular bodies and alpha-granules. Blood. 1999;94:3791–9.

    Article  CAS  PubMed  Google Scholar 

  17. Smyth NA, Murawski CD, Fortier LA, Cole BJ, Kennedy JG. Platelet-rich plasma in the pathologic processes of cartilage: review of basic science evidence. Arthroscopy. 2013;29:1399–409.

    Article  PubMed  Google Scholar 

  18. Uckan D, Kilic E, Sharafi P, Kazik M, Kaya F, Erdemli E, et al. Adipocyte differentiation defect in mesenchymal stromal cells of patients with malignant infantile osteopetrosis. Cytotherapy. 2009;11:392–402.

    Article  CAS  PubMed  Google Scholar 

  19. Pineda S, Pollack A, Stevenson S, Goldberg V, Caplan A. A semiquantitative scale for histologic grading of articular cartilage repair. Acta Anat. 1992;143:335–40.

    Article  CAS  PubMed  Google Scholar 

  20. Burdick JA, Mauck RL, Gorman JH 3rd, Gorman RC. Acellular biomaterials: an evolving alternative to cell-based therapies. Sci Transl Med. 2013;5:176ps4.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Lin CS, Lin G, Lue TF. Allogeneic and xenogeneic transplantation of adipose-derived stem cells in immunocompetent recipients without immunosuppressants. Stem Cells Dev. 2012;21:2770–8.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Wang Z, Zhu H, Dai S, Liu K, Ge C. Alleviation of medial meniscal transection-induced osteoarthritis pain in rats by human adipose derived mesenchymal stem cells. Stem Cell Investig. 2020;7:10.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Jang KM, Lee JH, Park CM, Song HR, Wang JH. Xenotransplantation of human mesenchymal stem cells for repair of osteochondral defects in rabbits using osteochondral biphasic composite constructs. Knee Surg Sports Traumatol Arthrosc. 2014;22:1434–44.

    Article  PubMed  Google Scholar 

  24. Li M, Luo X, Lv X, Liu V, Zhao G, Zhang X, et al. In vivo human adipose-derived mesenchymal stem cell tracking after intra-articular delivery in a rat osteoarthritis model. Stem Cell Res Ther. 2016;7:160.

    Article  PubMed  PubMed Central  Google Scholar 

  25. McKinney JM, Doan TN, Wang L, Deppen J, Reece DS, Pucha KA, et al. Therapeutic efficacy of intra-articular delivery of encapsulated human mesenchymal stem cells on early stage osteoarthritis. Eur Cell Mater. 2019;37:42–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Bull E, Madani SY, Sheth R, Seifalian A, Green M, Seifalian AM. Stem cell tracking using iron oxide nanoparticles. Int J Nanomedicine. 2014;9:1641–53.

    CAS  PubMed Central  PubMed  Google Scholar 

  27. Kim JE, Lee SM, Kim SH, Tatman P, Gee AO, Kim DH, et al. Effect of self-assembled peptide-mesenchymal stem cell complex on the progression of osteoarthritis in a rat model. Int J Nanomedicine. 2014;9 Suppl 1:141–57.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Saulnier N, Viguier E, Perrier-Groult E, Chenu C, Pillet E, Roger T, et al. Intra-articular administration of xenogeneic neonatal Mesenchymal Stromal Cells early after meniscal injury down-regulates metalloproteinase gene expression in synovium and prevents cartilage degradation in a rabbit model of osteoarthritis. Osteoarthritis Cartilage. 2015;23:122–33.

    Article  CAS  PubMed  Google Scholar 

  29. Dhinsa BS, Adesida AB. Current clinical therapies for cartilage repair, their limitation and the role of stem cells. Curr Stem Cell Res Ther. 2012;7:143–8.

    Article  CAS  PubMed  Google Scholar 

  30. Sun Y, Feng Y, Zhang CQ, Chen SB, Cheng XG. The regenerative effect of platelet-rich plasma on healing in large osteochondral defects. Int Orthop. 2010;34:589–97.

    Article  CAS  PubMed  Google Scholar 

  31. Kon E, Filardo G, Delcogliano M, Fini M, Salamanna F, Giavaresi G, et al. Platelet autologous growth factors decrease the osteochondral regeneration capability of a collagen-hydroxyapatite scaffold in a sheep model. BMC Musculoskelet Disord. 2010;11:220.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Hangody L, Dobos J, Baló E, Pánics G, Hangody LR, Berkes I. Clinical experiences with autologous osteochondral mosaicplasty in an athletic population: a 17-year prospective multicenter study. Am J Sports Med. 2010;38:1125–33.

    Article  PubMed  Google Scholar 

  33. Henderson I, Francisco R, Oakes B, Cameron J. Autologous chondrocyte implantation for treatment of focal chondral defects of the knee–a clinical, arthroscopic, MRI and histologic evaluation at 2 years. Knee. 2005;12:209–16.

    Article  PubMed  Google Scholar 

  34. Gooding CR, Bartlett W, Bentley G, Skinner JA, Carrington R, Flanagan A. A prospective, randomised study comparing two techniques of autologous chondrocyte implantation for osteochondral defects in the knee: Periosteum covered versus type I/III collagen covered. Knee. 2006;13:203–10.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was funded by Hacettepe University Research Fund (Grant No. THD-2018-16887). Erdi Özdemir, Abdülsamet Emet and Egemen Turhan decellularized the human placenta and performed the animal experiment. Emine Kılıç and Duygu Uçkan Çetinkaya proliferated the mesenchymal stem cells used in the study. Histological analysis was performed by Ramin Hashemihesar and Ali Celalettin Sinan Yürüker. All the authors had an outstanding contribution to the design of the study, analysis of the data and writing of the report. All authors reviewed final version of the manuscript.

Author information

Authors and Affiliations

  1. Department of Orthopedics and Traumatology, Faculty of Medicine, Hacettepe University, 06230, Ankara, Turkey

    Erdi Özdemir, Abdülsamet Emet & Egemen Turhan

  2. Department of Histology and Embryology, Faculty of Medicine, Istanbul Aydin University, 34295, Istanbul, Turkey

    Ramin Hashemihesar

  3. Department of Histology and Embryology, Faculty of Medicine, Uşak University, 64000, Uşak, Turkey

    Ali Celalettin Sinan Yürüker

  4. Center for Stem Cell Research and Development, Hacettepe University, 06100, Ankara, Turkey

    Emine Kılıç & Duygu Uçkan Çetinkaya

Authors
  1. Erdi Özdemir
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Abdülsamet Emet
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ramin Hashemihesar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ali Celalettin Sinan Yürüker
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Emine Kılıç
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Duygu Uçkan Çetinkaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Egemen Turhan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Erdi Özdemir.

Ethics declarations

Conflict of interest

Authors have declared that there is no conflict of interest.

Ethical statement

The animal studies were performed after receiving approval of the Institutional Animal Care and Use Committee (IACUC) in Hacettepe University (IACUC approval No. 2017/48-07).

Additional information

Publisher's Note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Özdemir, E., Emet, A., Hashemihesar, R. et al. Articular Cartilage Regeneration Utilizing Decellularized Human Placental Scaffold, Mesenchymal Stem Cells and Platelet Rich Plasma. Tissue Eng Regen Med 17, 901–908 (2020). https://doi.org/10.1007/s13770-020-00298-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13770-020-00298-w

Keywords

Search

Navigation