Skip to main content

Advertisement

SpringerLink
Log in

Engineering of Functional Cartilage Tissue Using Stem Cells from Synovial Lining: A Preliminary Study

  • Symposium: New Approaches to Allograft Transplantation
  • Published:
Clinical Orthopaedics and Related Research

Abstract

Stem cells derived from synovial lining—synovial lining-derived stem cells or SDSCs—are a promising cell source for cartilage tissue engineering. We hypothesized that negatively selected SDSCs would form cartilage constructs and conventionally passaged SDSCs would be contaminated with macrophages, inhibiting SDSC-based chondrogenesis. We mixed SDSCs with fibrin gel and seeded the cells into polyglycolic acid scaffolds. After 3 days of incubation with a proliferative growth factor cocktail (containing transforming growth factor β1 [TGF-β1], insulin-like growth factor I [IGF-I], and basic fibroblast growth factor [FGF-2]), the cell-fibrin-polyglycolic acid constructs were transferred into rotating bioreactor systems and cultured with a chondrogenic growth factor cocktail (TGF-β1/IGF-I) for up to 4 weeks. Tissue constructs based on negatively selected SDSCs had cartilaginous characteristics; were rich in glycosaminoglycans and collagen II; exhibited high expression of mRNA and protein for collagen II, aggrecan, and Sox 9; exhibited a negligible level of mRNA and protein for collagens I and X; and had an equilibrium modulus in the range of values measured for native human cartilage. Conventional passage yielded SDSCs with contaminating macrophages, which adversely affected the quality of tissue-engineered cartilage. We thus propose functional cartilage constructs could be engineered in vitro through the use of negatively isolated SDSCs.

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. 1A–I
Fig. 2A–J
Fig. 3A–H

Similar content being viewed by others

References

  1. Allard SA, Maini RN, Muirden KD. Cells and matrix expressing cartilage components in fibroblastic tissue in rheumatoid pannus. Scand J Rheumatol Suppl. 1988;76:125–129.

    Article  PubMed  CAS  Google Scholar 

  2. Bandara G, Georgescu HI, Lin CW, Evans CH. Synovial activation of chondrocytes: evidence for complex cytokine interactions. Agents Actions. 1991;34:285–288.

    Article  PubMed  CAS  Google Scholar 

  3. Blom AB, van Lent PL, Libregts S, Holthuysen AE, van der Kraan PM, van Rooijen N, van den Berg WB. Crucial role of macrophages in matrix metalloproteinase-mediated cartilage destruction during experimental osteoarthritis: involvement of matrix metalloproteinase 3. Arthritis Rheum. 2007;56:147–157.

    Article  PubMed  CAS  Google Scholar 

  4. Bondeson J, Wainwright SD, Lauder S, Amos N, Hughes CE. The role of synovial macrophages and macrophage-produced cytokines in driving aggrecanases, matrix metalloproteinases, and other destructive and inflammatory responses in osteoarthritis. Arthritis Res Ther. 2006;8:R187.

    Article  PubMed  CAS  Google Scholar 

  5. Chen AC, Bae WC, Schinagl RM, Sah RL. Depth- and strain-dependent mechanical and electromechanical properties of full-thickness bovine articular cartilage in confined compression. J Biomech. 2001;34:1–12.

    Article  PubMed  CAS  Google Scholar 

  6. Crawford A, Frazer A, Lippitt JM, Buttle DJ, Smith T. A case of chondromatosis indicates a synovial stem cell aetiology. Rheumatology (Oxford). 2006;45:1529–1533.

    Article  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  8. De Bari C, Dell’Accio F, Vandenabeele F, Vermeesch JR, Raymackers JM, Luyten FP. Skeletal muscle repair by adult human mesenchymal stem cells from synovial membrane. J Cell Biol. 2003;160:909–918.

    Article  PubMed  CAS  Google Scholar 

  9. Di Cesare PE, Carlson CS, Stollerman ES, Chen FS, Leslie M, Perris R. Expression of cartilage oligomeric matrix protein by human synovium. FEBS Lett. 1997;412:249–252.

    Article  PubMed  CAS  Google Scholar 

  10. Dodge GR, Hawkins D, Boesler E, Sakai L, Jimenez SA. Production of cartilage oligomeric matrix protein (COMP) by cultured human dermal and synovial fibroblasts. Osteoarthritis Cartilage. 1998;6:435–440.

    Article  PubMed  CAS  Google Scholar 

  11. Farndale RW, Buttle DJ, Barrett AJ. Improved quantitation and discrimination of sulphated glycosaminoglycans by use of dimethylmethylene blue. Biochim Biophys Acta. 1986;883:173–177.

    PubMed  CAS  Google Scholar 

  12. Fife RS, Caterson B, Myers SL. Identification of link proteins in canine synovial cell cultures and canine articular cartilage. J Cell Biol. 1985;100:1050–1055.

    Article  PubMed  CAS  Google Scholar 

  13. Fortier LA, Brofman PJ, Nixon AJ, Mohammed HO. Disparate chondrocyte metabolism in three-dimensional fibrin cultures derived from autogenous or commercially manufactured fibrinogen. Am J Vet Res. 1998;59:514–520.

    PubMed  CAS  Google Scholar 

  14. Fowler MR, Nathan CO, Abreo F. Synovial metaplasia, a specialized form of repair. Arch Pathol Lab Med. 2002;126:727–730.

    PubMed  Google Scholar 

  15. Gelse K, von der Mark K, Aigner T, Park J, Schneider H. Articular cartilage repair by gene therapy using growth factor-producing mesenchymal cells. Arthritis Rheum. 2003;48:430–441.

    Article  PubMed  CAS  Google Scholar 

  16. Gronthos S, Simmons PJ. The growth factor requirements of STRO-1-positive human bone marrow stromal precursors under serum-deprived conditions in vitro. Blood. 1995;85:929–940.

    PubMed  CAS  Google Scholar 

  17. Hamerman D, Smith C, Keiser HD, Craig R. Glycosaminoglycans produced by human synovial cell cultures. Coll Relat Res. 1982;2:313–329.

    PubMed  CAS  Google Scholar 

  18. Homminga GN, Buma P, Koot HW, van der Kraan PM, van den Berg WB. Chondrocyte behavior in fibrin glue in vitro. Acta Orthop Scand. 1993;64:441–445.

    Article  PubMed  CAS  Google Scholar 

  19. Hunziker EB. Growth-factor-induced healing of partial-thickness defects in adult articular cartilage. Osteoarthritis Cartilage. 2001;9:22–32.

    Article  PubMed  CAS  Google Scholar 

  20. Hunziker EB, Rosenberg LC. Repair of partial-thickness defects in articular cartilage: cell recruitment from the synovial membrane. J Bone Joint Surg Am. 1996;78:721–733.

    PubMed  CAS  Google Scholar 

  21. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25:402–408.

    Article  PubMed  CAS  Google Scholar 

  22. Maurice H, Crone M, Watt I. Synovial chondromatosis. J Bone Joint Surg Br. 1988;70:807–811.

    PubMed  CAS  Google Scholar 

  23. Miyamoto H, Sakashita H, Wilson DF, Goss AN. Synovial chondromatosis of the temporomandibular joint. Br J Oral Maxillofac Surg. 2000;38:205–208.

    Article  PubMed  CAS  Google Scholar 

  24. Mochizuki T, Muneta T, Sakaguchi Y, Nimura A, Yokoyama A, Koga H, Sekiya I. Higher chondrogenic potential of fibrous synovium- and adipose synovium-derived cells compared with subcutaneous fat-derived cells: distinguishing properties of mesenchymal stem cells in humans. Arthritis Rheum. 2006;54:843–853.

    Article  PubMed  CAS  Google Scholar 

  25. Nishimura K, Solchaga LA, Caplan AI, Yoo JU, Goldberg VM, Johnstone B. Chondroprogenitor cells of synovial tissue. Arthritis Rheum. 1999;42:2631–2637.

    Article  PubMed  CAS  Google Scholar 

  26. Pacifici M, Koyama E, Iwamoto M, Gentili C. Development of articular cartilage: what do we know about it and how may it occur? Connect Tissue Res. 2000;41:175–184.

    Article  PubMed  CAS  Google Scholar 

  27. Pei M, He F, Vunjak-Novakovic G. Synovium-derived stem cell-based chondrogenesis. Differentiation. 2008; Doi: 10.1111/j.1432-0436.2008.00299.x.

  28. Pei M, Seidel J, Vunjak-Novakovic G, Freed LE. Growth factors for sequential cellular de- and re-differentiation in tissue engineering. Biochem Biophys Res Commun. 2002;294:149–154.

    Article  PubMed  CAS  Google Scholar 

  29. Pei M, Solchaga LA, Seidel J, Zeng L, Vunjak-Novakovic G, Caplan AI, Freed LE. Bioreactors mediate the effectiveness of tissue engineering scaffolds. FASEB J. 2002;16:1691–1694.

    PubMed  CAS  Google Scholar 

  30. Recklies AD, Baillargeon L, White C. Regulation of cartilage oligomeric matrix protein synthesis in human synovial cells and articular chondrocytes. Arthritis Rheum. 1998;41:997–1006.

    Article  PubMed  CAS  Google Scholar 

  31. Sakaguchi Y, Sekiya I, Yagishita K, Muneta T. Comparison of human stem cells derived from various mesenchymal tissues: superiority of synovium as a cell source. Arthritis Rheum. 2005;52:2521–2529.

    Article  PubMed  Google Scholar 

  32. Sakimura K, Matsumoto T, Miyamoto C, Osaki M, Shindo H. Effects of insulin-like growth factor I on transforming growth factor beta1 induced chondrogenesis of synovium-derived mesenchymal stem cells cultured in a polyglycolic acid scaffold. Cells Tissues Organs. 2006;183:55–61.

    Article  PubMed  CAS  Google Scholar 

  33. Shintani N, Hunziker EB. Chondrogenic differentiation of bovine synovium: bone morphogenetic proteins 2 and 7 and transforming growth factor beta1 induce the formation of different types of cartilaginous tissue. Arthritis Rheum. 2007;56:1869–1879.

    Article  PubMed  CAS  Google Scholar 

  34. Shirasawa S, Sekiya I, Sakaguchi Y, Yagishita K, Ichinose S, Muneta T. In vitro chondrogenesis of human synovium-derived mesenchymal stem cells: optimal condition and comparison with bone marrow-derived cells. J Cell Biochem. 2006;97:84–97.

    Article  PubMed  CAS  Google Scholar 

  35. Sim FH, Dahlin DC, Ivins JC. Extra-articular synovial chondromatosis. J Bone Joint Surg Am. 1977;59:492–495.

    PubMed  CAS  Google Scholar 

  36. Theoret CL, Barber SM, Moyana T, Townsend HG, Archer JF. Repair and function of synovium after arthroscopic synovectomy of the dorsal compartment of the equine antebrachiocarpal joint. Vet Surg. 1996;25:142–153.

    Article  PubMed  CAS  Google Scholar 

  37. Wexler SA, Donaldson C, Denning-Kendall P, Rice C, Bradley B, Hows JM. Adult bone marrow is a rich source of human mesenchymal ‘stem’ cells but umbilical cord and mobilized adult blood are not. Br J Haematol. 2003;121:368–374.

    Article  PubMed  Google Scholar 

  38. Xue C, Takahashi M, Hasunuma T, Aono H, Yamamoto K, Yoshino S, Sumida T, Nishioka K. Characterisation of fibroblast-like cells in pannus lesions of patients with rheumatoid arthritis sharing properties of fibroblasts and chondrocytes. Ann Rheum Dis. 1997;56:262–267.

    Article  PubMed  CAS  Google Scholar 

  39. Yang X, Chen L, Xu X, Li C, Huang C, Deng CX. TGF-beta/Smad3 signals repress chondrocyte hypertrophic differentiation and are required for maintaining articular cartilage. J Cell Biol. 2001;153:35–46.

    Article  PubMed  CAS  Google Scholar 

  40. Yokoyama A, Sekiya I, Miyazaki K, Ichinose S, Hata Y, Muneta T. In vitro cartilage formation of composites of synovium-derived mesenchymal stem cells with collagen gel. Cell Tissue Res. 2005;322:289–298.

    Article  PubMed  CAS  Google Scholar 

  41. Yoshimura H, Muneta T, Nimura A, Yokoyama A, Koga H, Sekiya I. Comparison of rat mesenchymal stem cells derived from bone marrow, synovium, periosteum, adipose tissue, and muscle. Cell Tissue Res. 2007;327:449–462.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Suzanne Smith for editing the manuscript and A.B. Billings for performing a post-hoc power analysis for the samples.

Author information

Authors and Affiliations

  1. Tissue Engineering Laboratory, Department of Orthopaedics, West Virginia University, 3943 Health Sciences Center South, PO Box 9196, Morgantown, WV, 26506-9196, USA

    Ming Pei MD, PhD, Fan He BS & Vincent L. Kish ASEE

  2. Department of Biomedical Engineering, Columbia University, New York, NY, USA

    Gordana Vunjak-Novakovic PhD

Authors
  1. Ming Pei MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fan He BS
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vincent L. Kish ASEE
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gordana Vunjak-Novakovic PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ming Pei MD, PhD.

Additional information

One or more of the authors (MP) has received funding from the Musculoskeletal Transplant Foundation.

Each author certifies that his or her institution has approved the animal protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research.

About this article

Cite this article

Pei, M., He, F., Kish, V.L. et al. Engineering of Functional Cartilage Tissue Using Stem Cells from Synovial Lining: A Preliminary Study. Clin Orthop Relat Res 466, 1880–1889 (2008). https://doi.org/10.1007/s11999-008-0316-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11999-008-0316-2

Keywords

Search

Navigation