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Anti-Inflammatory Effect of Adipose-Derived Stromal Vascular Fraction on Osteoarthritic Temporomandibular Joint Synoviocytes

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Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Background:

Osteoarthritis (OA) in the temporomandibular joint (TMJ) in the TMJ (TMJ-OA) is difficult to treat, and new alternative treatments are needed. Recently, adipose-derived stem cells (ASCs) have been introduced as a promising cell source because of their anti-inflammatory effects. However, the cost and availability of these cells limited broader applications of stem cell therapy. Thus, Thus, stromal vascular fraction (SVF) containing sufficient amount of ASCs at low cost can be an alternative. In this study, we aimed to demonstrate the use of uncultured, optimally isolated SVF for the treatment of TMJ-OA.

Methods:

First, we optimized the method of isolation to harvest high-quality SVFs with a large yield of ASCs. Then, we analyzed the quantity of ASCs in the SVF and performed characterization of stem cell homology. Subsequently, to evaluate the anti-inflammatory effect of high-quality SVF, an in vitro study was performed to assess the expression patterns of inflammatory cytokines including prostaglandin E2 (PGE2), IL-6, and CXCL8/IL-8, COX2, TNF, IFN, CCL2/MCP-1 and CCL5/RANTES in co-culture with synoviocytes derived from the synovial fluid in the TMJ-OA patients.

Results:

The SVF containing approximately 32% ASCs was isolated via the our optimized isolation method. The SVF significantly down-regulated certain inflammatory cytokines such as PGE2, CXCL8/IL-8 in TMJ-OA tissue-derived synoviocytes.

Conclusion:

Although further study is needed, our study suggests that transplantation of adipose tissue-derived SVF cells might be a feasible and a novel therapeutic option for TMJ-OA in the future.

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References

  1. Stohler CS. Craniofacial pain and motor function: pathogenesis, clinical correlates, and implications. Crit Rev Oral Biol Med. 1999;10:504–18.

    Article  CAS  Google Scholar 

  2. Dimitroulis G. The role of surgery in the management of disorders of the temporomandibular joint: a critical review of the literature: part 2. Int J Oral Maxillofac Surg. 2005;34:231–7.

    CAS  PubMed  Google Scholar 

  3. Loeser RF, Goldring SR, Scanzello CR, Goldring MB. Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum. 2012;64:1697–707.

    Article  Google Scholar 

  4. Sellam J, Berenbaum F. The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis. Nat Rev Rheumatol. 2010;6:625–35.

    Article  CAS  Google Scholar 

  5. Goldring M, Otero M, Tsuchimochi K, Ijiri K, Li Y. Defining the roles of inflammatory and anabolic cytokines in cartilage metabolism. Ann Rheum Dis. 2008;67:iii75–82.

    Article  CAS  Google Scholar 

  6. Scanzello CR, Goldring SR. The role of synovitis in osteoarthritis pathogenesis. Bone. 2012;51:249–57.

    Article  CAS  Google Scholar 

  7. Hunter DJ. Pharmacologic therapy for osteoarthritis—the era of disease modification. Nat Rev Rheumatol. 2011;7:13–22.

    Article  CAS  Google Scholar 

  8. Jorgensen C, Noël D. Mesenchymal stem cells in osteoarticular diseases. Regen Med. 2011;6:44–51.

    Article  CAS  Google Scholar 

  9. ter Huurne M, Schelbergen R, Blattes R, Blom A, de Munter W, Grevers LC, et al. Antiinflammatory and chondroprotective effects of intraarticular injection of adipose-derived stem cells in experimental osteoarthritis. Arthritis Rheum. 2012;64:3604–13.

    Article  Google Scholar 

  10. Desando G, Cavallo C, Sartoni F, Martini L, Parrilli A, Veronesi F, et al. Intra-articular delivery of adipose derived stromal cells attenuates osteoarthritis progression in an experimental rabbit model. Arthritis Res Ther. 2013;15:R22.

    Article  CAS  Google Scholar 

  11. Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, et al. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 2001;7:211–28.

    Article  CAS  Google Scholar 

  12. Rodriguez AM, Elabd C, Amri EZ, Ailhaud G, Dani C. The human adipose tissue is a source of multipotent stem cells. Biochimie. 2005;87:125–8.

    Article  CAS  Google Scholar 

  13. Awad HA, Wickham MQ, Leddy HA, Gimble JM, Guilak F. Chondrogenic differentiation of adipose-derived adult stem cells in agarose, alginate, and gelatin scaffolds. Biomaterials. 2004;25:3211–22.

    Article  CAS  Google Scholar 

  14. Strem BM, Hicok KC, Zhu M, Wulur I, Alfonso Z, Schreiber RE, et al. Multipotential differentiation of adipose tissue-derived stem cells. Keio J Med. 2005;54:132–41.

    Article  CAS  Google Scholar 

  15. Grigolo B, Roseti L, Neri S, Gobbi P, Jensen P, Major EO, et al. Human articular chondrocytes immortalized by HPV-16 E6 and E7 genes: maintenance of differentiated phenotype under defined culture conditions. Osteoarthritis Cartilage. 2002;10:879–89.

    Article  CAS  Google Scholar 

  16. Lisignoli G, Grassi F, Piacentini A, Cocchini B, Remiddi G, Bevilacqua C, et al. Hyaluronan does not affect cytokine and chemokine expression in osteoarthritic chondrocytes and synoviocytes. Osteoarthritis Cartilage. 2001;9:161–8.

    Article  CAS  Google Scholar 

  17. Lee YH, Park HK, Auh QS, Nah H, Lee JS, Moon HJ, et al. Emerging potential of exosomes in regenerative medicine for temporomandibular joint osteoarthritis. Int J Mol Sci. 2020;24:E1541.

    Article  Google Scholar 

  18. Scanzello CR, McKeon B, Swaim BH, DiCarlo E, Asomugha EU, Kanda V, et al. Synovial inflammation in patients undergoing arthroscopic meniscectomy: molecular characterization and relationship to symptoms. Arthritis Rheum. 2011;63:391–400.

    Article  Google Scholar 

  19. Prockop DJ. Marrow stromal cells as stem cells for nonhematopoietic tissues. Science. 1997;276:71–4.

    Article  CAS  Google Scholar 

  20. Lee OK, Kuo TK, Chen WM, Lee KD, Hsieh SL, Chen TH. Isolation of multipotent mesenchymal stem cells from umbilical cord blood. Blood. 2004;103:1669–75.

    Article  CAS  Google Scholar 

  21. Corcione A, Benvenuto F, Ferretti E, Giunti D, Cappiello V, Cazzanti F, et al. Human mesenchymal stem cells modulate B-cell functions. Blood. 2006;107:367–72.

    Article  CAS  Google Scholar 

  22. Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, et al. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet. 2008;371:1579–86.

    Article  Google Scholar 

  23. Duijvestein M, Vos AC, Roelofs H, Wildenberg ME, Wendrich BB, Verspaget HW, et al. Autologous bone marrow-derived mesenchymal stromal cell treatment for refractory luminal Crohn’s disease: results of a phase I study. Gut. 2010;59:1662–9.

    Article  Google Scholar 

  24. Ogura N, Tobe M, Sakamaki H, Nagura H, Abiko Y, Kondoh T. Tumor necrosis factor-alpha increases chemokine gene expression and production in synovial fibroblasts from human temporomandibular joint. J Oral Pathol Med. 2005;34:357–63.

    Article  CAS  Google Scholar 

  25. Ogura N, Satoh K, Akutsu M, Tobe M, Kuyama K, Kuboyama N, et al. MCP-1 production in temporomandibular joint inflammation. J Dent Res. 2010;89:1117–22.

    Article  CAS  Google Scholar 

  26. Garza JR, Campbell RE, Tjoumakaris FP, Freedman KB, Miller LS, Santa Maria D, et al. Clinical efficacy of intra-articular mesenchymal stromal cells for the treatment of knee osteoarthritis: a double-blinded prospective randomized controlled clinical trial. Am J Sports Med. 2020;48:588–98.

    Article  Google Scholar 

  27. Bonfield TL, Nolan Koloze MT, Lennon DP, Caplan AI. Defining human mesenchymal stem cell efficacy in vivo. J Inflamm (Lond). 2010;7:51.

    Article  Google Scholar 

  28. Prockop DJ, Oh JY. Mesenchymal stem/stromal cells (MSCs): role as guardians of inflammation. Mol Ther. 2012;20:14–20.

    Article  CAS  Google Scholar 

  29. Cui SJ, Zhang T, Fu Y, Liu Y, Gan YH, Zhou YH, et al. DPSCs attenuate experimental progressive TMJ arthritis by inhibiting the STAT1 pathway. J Dent Res. 2020;99:446–55.

    Article  CAS  Google Scholar 

  30. Jiang L, Xu K, Li J, Zhou X, Xu L, Wu Z, et al. Nesfatin-1 suppresses interleukin-1β-induced inflammation, apoptosis, and cartilage matrix destruction in chondrocytes and ameliorates osteoarthritis in rats. Aging (Albany NY). 2020;12:1760–77.

    Article  Google Scholar 

  31. Xia L, Zhang HX, Xing ML, Xu YB, Li P, Huang LK, et al. Knockdown of PRMT1 suppresses IL-1β-induced cartilage degradation and inflammatory responses in human chondrocytes through Gli1-mediated Hedgehog signaling pathway. Mol Cell Biochem. 2018;438:17–24.

    Article  CAS  Google Scholar 

  32. Xue XT, Kou XX, Li CS, Bi RY, Meng Z, Wang XD, et al. Progesterone attenuates temporomandibular joint inflammation through inhibition of NF-κB pathway in ovariectomized rats. Sci Rep. 2017;7:15334.

    Article  Google Scholar 

  33. Appleton I, Tomlinson A, Willoughby DA. Induction of cyclo-oxygenase and nitric oxide synthase in inflammation. Adv Pharmacol. 1996;35:27–78.

    Article  CAS  Google Scholar 

  34. Goldring MB, Otero M, Plumb DA, Dragomir C, Favero M, El Hachem K, et al. Roles of inflammatory and anabolic cytokines in cartilage metabolism: signals and multiple effectors converge upon MMP-13 regulation in osteoarthritis. Eur Cell Mater. 2011;21:202–20.

    Article  CAS  Google Scholar 

  35. Caron MM, Emans PJ, Sanen K, Surtel DA, Cremers A, Ophelders D, et al. The role of prostaglandins and COX-enzymes in chondrogenic differentiation of ATDC5 progenitor cells. PLoS One. 2016;11:e0153162.

    Article  Google Scholar 

  36. Barrio L, Cuevas VD, Menta R, Mancheño-Corvo P, delaRosa O, Dalemans W, et al. Human adipose tissue-derived mesenchymal stromal cells promote B-cell motility and chemoattraction. Cytotherapy. 2014;16:1692–9.

    Article  CAS  Google Scholar 

  37. Yañez R, Oviedo A, Aldea M, Bueren JA, Lamana ML. Prostaglandin E2 plays a key role in the immunosuppressive properties of adipose and bone marrow tissue-derived mesenchymal stromal cells. Exp Cell Res. 2010;316:3109–23.

    Article  Google Scholar 

  38. Lee CC, Hirasawa N, Garcia KG, Ramanathan D, Kim KD. Stem and progenitor cell microenvironment for bone regeneration and repair. Regen Med. 2019;14:693–702.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (HI10V-0090-010014). This study was also supported by the Korean Incorporated Association of Temporomandibular Joint.

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Correspondence to Bu-Kyu Lee.

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This study was approved by the institutional review board (IRB) of Asan Medical Center (S2013-0409-0001). Informed written consent was provided by each patient involved in the study.

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Kim, H., Lee, BK. Anti-Inflammatory Effect of Adipose-Derived Stromal Vascular Fraction on Osteoarthritic Temporomandibular Joint Synoviocytes. Tissue Eng Regen Med 17, 351–362 (2020). https://doi.org/10.1007/s13770-020-00268-2

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  • DOI: https://doi.org/10.1007/s13770-020-00268-2

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