Skip to main content
SpringerLink
Log in

Therapeutic possibility of human fetal cartilage-derived progenitor cells in rat arthritis model

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

Abstract

Fetal cartilage-derived progenitor cells (FCPCs) are a novel cell source for tissue engineering and cell therapy. Previously, cells from various fetal tissues were shown to have immune-modulatory activity just like mesenchymal stem cells. In this study, we investigated the cytotoxicity and therapeutic possibility of FCPCs as a potential cell therapy for arthritis in vivo. To evaluate the acute toxicity and safety, FCPCs were labeled with PKH-26 and subjected to intra-articular injection in rats. When examined at 1 and 2 weeks, the PKH-26 labeled FCPCs were observed only in the synovial membrane but not in other organs. There were no changes either in the white blood cells, red blood cells, and platelets in the hematological analysis and in the weight of the internal organs at 1 week. Therapeutic effect of FCPCs was examined on the complete Freund’s adjuvant (CFA)-induced knee arthritis in rats in comparison with triamcinolone, a representative anti-arthritis drug. When inflammation-related edema of the arthritic knee joint was measured by the knee circumference, it increased significantly from the beginning and maintained until the end of measurement in the CFA group, which decreased back rapidly from 1 day in the triamcinolone group and slowly after 7 days in the FCPCs group. In the histological analysis, both triamcinolone and FCPCs decreased the infiltration of neutrophils and lymphocytes into the arthritic synovial membrane gradually at 3 and 7 days. These results suggest that FCPCs shows low toxicity or immune rejection when injected in the synovial cavity and have a therapeutic potential on the synovial arthritis in the rat model.

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

Similar content being viewed by others

References

  1. Wei X, Yang X, Han ZP, Qu FF, Shao L, Shi YF. Mesenchymal stem cells: a new trend for cell therapy. Acta Pharmacol Sin 2013;34:747–754.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Deans RJ, Moseley AB. Mesenchymal stem cells: biology and potential clinical uses. Exp Hematol 2000;28:875–884.

    Article  CAS  PubMed  Google Scholar 

  3. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999;284:143–147.

    Article  CAS  PubMed  Google Scholar 

  4. Baksh D, Song L, Tuan RS. Adult mesenchymal stem cells: characterization, differentiation, and application in cell and gene therapy. J Cell Mol Med 2004;8: 301–316.

    Article  CAS  PubMed  Google Scholar 

  5. Short B, Brouard N, Occhiodoro-Scott T, Ramakrishnan A, Simmons PJ. Mesenchymal stem cells. Arch Med Res 2003;34:565–571.

    Article  CAS  PubMed  Google Scholar 

  6. Quarto R, Thomas D, Liang CT. Bone progenitor cell deficits and the ageassociated decline in bone repair capacity. Calcif Tissue Int 1995;56:123–129.

    Article  CAS  PubMed  Google Scholar 

  7. D’Ippolito G, Schiller PC, Ricordi C, Roos BA, Howard GA. Age-related osteogenic potential of mesenchymal stromal stem cells from human vertebral bone marrow. J Bone Miner Res 1999;14:1115–1122.

    Article  PubMed  Google Scholar 

  8. Bianco P, Riminucci M, Gronthos S, Robey PG. Bone marrow stromal stem cells: nature, biology, and potential applications. Stem Cells 2001; 19:180–192.

    Article  CAS  PubMed  Google Scholar 

  9. Poncelet AJ, Vercruysse J, Saliez A, Gianello P. Although pig allogeneic mesenchymal stem cells are not immunogenic in vitro, intracardiac injection elicits an immune response in vivo. Transplantation 2007;83:783–790.

    Article  PubMed  Google Scholar 

  10. Charron D. Allogenicity & immunogenicity in regenerative stem cell therapy. Indian J Med Res 2013;138:749–754.

    PubMed Central  CAS  PubMed  Google Scholar 

  11. Joshi M, B Patil P, He Z, Holgersson J, Olausson M, Sumitran-Holgersson S. Fetal liver-derived mesenchymal stromal cells augment engraftment of transplanted hepatocytes. Cytotherapy 2012;14:657–669.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Guillot PV, Gotherstrom C, Chan J, Kurata H, Fisk NM. Human firsttrimester fetal MSC express pluripotency markers and grow faster and have longer telomeres than adult MSC. Stem Cells 2007;25:646–654.

    Article  CAS  PubMed  Google Scholar 

  13. Campagnoli C, Roberts IA, Kumar S, Bennett PR, Bellantuono I, Fisk NM. Identification of mesenchymal stem/progenitor cells in human firsttrimester fetal blood, liver, and bone marrow. Blood 2001;98:2396–2402.

    Article  CAS  PubMed  Google Scholar 

  14. De Buys Roessingh AS, Hohlfeld J, Scaletta C, Hirt-Burri N, Gerber S, Hohlfeld P, et al. Development, characterization, and use of a fetal skin cell bank for tissue engineering in wound healing. Cell Transplant 2006; 15:823–834.

    Article  PubMed  Google Scholar 

  15. Hohlfeld J, de Buys Roessingh A, Hirt-Burri N, Chaubert P, Gerber S, Scaletta C, et al. Tissue engineered fetal skin constructs for paediatric burns. Lancet 2005;366:840–842.

    Article  PubMed  Google Scholar 

  16. Quintin A, Hirt-Burri N, Scaletta C, Schizas C, Pioletti DP, Applegate LAA. Consistency and safety of cell banks for research and clinical use: preliminary analysis of fetal skin banks. Cell Transplant 2007;16:675–684.

    Article  PubMed  Google Scholar 

  17. Quintin A, Schizas C, Scaletta C, Jaccoud S, Applegate LA, Pioletti DPP. Plasticity of fetal cartilaginous cells. Cell Transplant 2010;19:1349–1357.

    Article  PubMed  Google Scholar 

  18. Kovacsovics-Bankowski M, Mauch K, Raber A, Streeter PR, Deans RJ, Maziarz RT, et al. Pre-clinical safety testing supporting clinical use of allogeneic multipotent adult progenitor cells. Cytotherapy 2008;10:730–742.

    Article  CAS  PubMed  Google Scholar 

  19. Seibel J, Bodié K, Weber S, Bury D, Kron M, Blaich G. Comparison of haematology, coagulation and clinical chemistry parameters in blood samples from the sublingual vein and vena cava in Sprague-Dawley rats. Lab Anim 2010;44:344–351.

    Article  CAS  PubMed  Google Scholar 

  20. Bevaart L, Vervoordeldonk MJ, Tak PP. Evaluation of therapeutic targets in animal models of arthritis: how does it relate to rheumatoid arthritis? Arthritis Rheum 2010;62:2192–2205.

    Article  CAS  PubMed  Google Scholar 

  21. Clark DD, Weckesser ECC. The influence of triamcinolone acetonide on joint stiffness in the rat. J Bone Joint Surg Am 1971;53:1409–1414.

    CAS  PubMed  Google Scholar 

  22. Wright HL, Moots RJ, Bucknall RC, Edwards SWW. Neutrophil function in inflammation and inflammatory diseases. Rheumatology (Oxford) 2010; 49:1618–1631.

    Article  CAS  Google Scholar 

  23. Djouad F, Bouffi C, Ghannam S, Noël D, Jorgensen C. Mesenchymal stem cells: innovative therapeutic tools for rheumatic diseases. Nat Rev Rheumatol 2009;5:392–399.

    Article  CAS  PubMed  Google Scholar 

  24. González MA, Gonzalez-Rey E, Rico L, Büscher D, Delgado M. Treatment of experimental arthritis by inducing immune tolerance with human adipose-derived mesenchymal stem cells. Arthritis Rheum 2009;60: 1006–1019.

    Article  PubMed  Google Scholar 

  25. Krattinger N, Applegate LA, Biver E, Pioletti DP, Caverzasio J. Regulation of proliferation and differentiation of human fetal bone cells. Eur Cell Mater 2011;21:46–58.

    CAS  PubMed  Google Scholar 

  26. Montjovent MO, Mark S, Mathieu L, Scaletta C, Scherberich A, Delabarde C, et al. Human fetal bone cells associated with ceramic reinforced PLA scaffolds for tissue engineering. Bone 2008;42:554–564.

    Article  CAS  PubMed  Google Scholar 

  27. Cohen S, Leshansky L, Zussman E, Burman M, Srouji S, Livne E, et al. Repair of full-thickness tendon injury using connective tissue progenitors efficiently derived from human embryonic stem cells and fetal tissues. Tissue Eng Part A 2010;16:3119–3137.

    Article  PubMed  Google Scholar 

  28. Foglia RP, DiPreta J, Statter MB, Donahoe PKK. Fetal allograft survival in immunocompetent recipients is age dependent and organ specific. Ann Surg 1986;204:402–410.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Ramelet AA, Hirt-Burri N, Raffoul W, Scaletta C, Pioletti DP, Offord E, et al. Chronic wound healing by fetal cell therapy may be explained by differential gene profiling observed in fetal versus old skin cells. Exp Gerontol 2009;44:208–218.

    Article  CAS  PubMed  Google Scholar 

  30. Applegate LA, Scaletta C, Hirt-Burri N, Raffoul W, Pioletti D. Whole-cell bioprocessing of human fetal cells for tissue engineering of skin. Skin Pharmacol Physiol 2009;22:63–73.

    Article  CAS  PubMed  Google Scholar 

  31. Götherström C, Ringdén O, Tammik C, Zetterberg E, Westgren M, Le Blanc K. Immunologic properties of human fetal mesenchymal stem cells. Am J Obstet Gynecol 2004;190:239–245.

    Article  PubMed  Google Scholar 

  32. Montjovent MO, Bocelli-Tyndall C, Scaletta C, Scherberich A, Mark S, Martin I, et al. In vitro characterization of immune-related properties of human fetal bone cells for potential tissue engineering applications. Tissue Eng Part A 2009;15:1523–1532.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Molecular Science & Technology, Ajou University, Suwon, Korea

    Su Jeong Lee, Hyun Ju Oh, Minh-Dung Truong & Byoung-Hyun Min

  2. Department of Pathology, School of Medicine, Ajou University, Suwon, Korea

    Kyi Beom Lee

  3. Inha Research Institute for Medical Sciences, Inha University College of Medicine, Incheon, Korea

    Jiyoung Kim

  4. Cell Therapy Center, Ajou University Medical Center, Suwon, Korea

    Young Jick Kim & Byoung-Hyun Min

  5. Department of Physiology, Inha University College of Medicine, Incheon, Korea

    So Ra Park

  6. Department of Orthopedic Surgery, School of Medicine, Ajou University, 206 Worldcup-ro, Yeongtong-gu, Suwon, 443-749, Korea

    Byoung-Hyun Min

Authors
  1. Su Jeong Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hyun Ju Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Minh-Dung Truong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kyi Beom Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jiyoung Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Young Jick Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. So Ra Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Byoung-Hyun Min
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Byoung-Hyun Min.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, S.J., Oh, H.J., Truong, MD. et al. Therapeutic possibility of human fetal cartilage-derived progenitor cells in rat arthritis model. Tissue Eng Regen Med 12 (Suppl 2), 147–154 (2015). https://doi.org/10.1007/s13770-015-0441-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13770-015-0441-4

Key Words

Search

Navigation