Stem cell therapy in knee osteoarthritis, a recent literature review

Year 2023, Volume: 40 Issue: 2, 383 - 389, 19.07.2023

Alparslan Yurtbay , Ferhat Say

Abstract

Cell-based therapy and novel approaches using mesenchymal stromal cells (MSCs) has been explored in recent years as a new regenerative therapy for knee osteoarthritis. MSCs are envisioned as the most extensively explored new therapeutic drugs in the treatment of cell-based osteoarthritis due to their ability to differentiate into chondrocytes and their immunomodulatory properties. Various procedures for cell selection and preparation have been described in studies on MSCs. This article focuses on a review of the available literature on MSC based cell therapy in primary knee osteoarthritis. Promising results have been obtained for cartilage repair in around thirty human studies. These results are like other cartilage repair methods, with good results in approximately 80% of the cases. However, the number of patients in stem cell studies is small and the follow-up period is very short. The new cartilage formed is a repair tissue and does not have the original cartilage structure. Therefore, there is not enough information about the long-term results of this treatment. It has not been shown to be superior to other cartilage repair methods. Orthopedic use of stem cells is still in its infancy. Although the results obtained are promising, they are not yet included in standard treatment protocols. Stem cell research continues all over the world, but the ideal application method is unknown. There is a need for further clinical studies with a larger patient populations and longer follow-up periods.

Keywords

cartilage, mesenchymal stromal cells, osteoarthritis, regenerative therapy, knee

References

• 1. Safiri S, Kolahi AA, Smith E, Hill C, Bettampadi D, Mansournia MA, et al. Global, regional and national burden of osteoarthritis 1990-2017: a systematic analysis of the Global Burden of Disease Study 2017. Ann Rheum Dis. 2020;79(6):819-28. Epub 2020/05/14. doi: 10.1136/annrheumdis-2019-216515. PubMed PMID: 32398285.
• 2. Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, et al. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum. 1986;29(8):1039-49. Epub 1986/08/01. doi: 10.1002/art.1780290816. PubMed PMID: 3741515.
• 3. Arden N, Nevitt MC. Osteoarthritis: epidemiology. Best Pract Res Clin Rheumatol. 2006;20(1):3-25. Epub 2006/02/18. doi: 10.1016/j.berh.2005.09.007. PubMed PMID: 16483904.
• 4. Dobson GP, Letson HL, Grant A, McEwen P, Hazratwala K, Wilkinson M, et al. Defining the osteoarthritis patient: back to the future. Osteoarthritis Cartilage. 2018;26(8):1003-7. Epub 2018/05/19. doi: 10.1016/j.joca.2018.04.018. PubMed PMID: 29775734.
• 5. Murphy C, Withrow J, Hunter M, Liu Y, Tang YL, Fulzele S, et al. Emerging role of extracellular vesicles in musculoskeletal diseases. Mol Aspects Med. 2018;60:123-8. Epub 2017/10/03. doi: 10.1016/j.mam.2017.09.006. PubMed PMID: 28965750; PubMed Central PMCID: PMC5856577.
• 6. Tu J, Huang W, Zhang W, Mei J, Yu Z, Zhu C. TWIST1-MicroRNA-10a-MAP3K7 Axis Ameliorates Synovitis of Osteoarthritis in Fibroblast-like Synoviocytes. Mol Ther Nucleic Acids. 2020;22:1107-20. Epub 2020/12/10. doi: 10.1016/j.omtn.2020.10.020. PubMed PMID: 33294296; PubMed Central PMCID: PMC7691159.
• 7. Goldring MB. The role of the chondrocyte in osteoarthritis. Arthritis Rheum. 2000;43(9):1916-26. Epub 2000/10/03. doi: 10.1002/1529-0131(200009)43:9<1916::AID-ANR2>3.0.CO;2-I. PubMed PMID: 11014341.
• 8. 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(6):R187. Epub 2006/12/21. doi: 10.1186/ar2099. PubMed PMID: 17177994; PubMed Central PMCID: PMC1794533.
• 9. Intema F, Hazewinkel HAW, Gouwens D, Bijlsma JWJ, Weinans H, Lafeber FPJG, et al. In early OA, thinning of the subchondral plate is directly related to cartilage damage: results from a canine ACLT-meniscectomy model. Osteoarthritis Cartilage. 2010;18(5):691-8. doi: 10.1016/j.joca.2010.01.004. PubMed PMID: WOS:000278175600014.
• 10. Mancuso P, Raman S, Glynn A, Barry F, Murphy JM. Mesenchymal Stem Cell Therapy for Osteoarthritis: The Critical Role of the Cell Secretome. Frontiers in bioengineering and biotechnology. 2019;7:9-. doi: 10.3389/fbioe.2019.00009. PubMed PMID: 30761298.
• 11. Musumeci G, Aiello FC, Szychlinska MA, Di Rosa M, Castrogiovanni P, Mobasheri A. Osteoarthritis in the XXIst century: risk factors and behaviours that influence disease onset and progression. Int J Mol Sci. 2015;16(3):6093-112. Epub 2015/03/19. doi: 10.3390/ijms16036093. PubMed PMID: 25785564; PubMed Central PMCID: PMC4394521.
• 12. Kolasinski SL, Neogi T, Hochberg MC, Oatis C, Guyatt G, Block J, et al. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee. Arthritis Care Res (Hoboken). 2020;72(2):149-62. Epub 2020/01/08. doi: 10.1002/acr.24131. PubMed PMID: 31908149.
• 13. Cross M, Smith E, Hoy D, Nolte S, Ackerman I, Fransen M, et al. The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis. 2014;73(7):1323-30. Epub 2014/02/21. doi: 10.1136/annrheumdis-2013-204763. PubMed PMID: 24553908.
• 14. Xiang XN, Zhu SY, He HC, Yu X, Xu Y, He CQ. Mesenchymal stromal cell-based therapy for cartilage regeneration in knee osteoarthritis. Stem Cell Res Ther. 2022;13(1):14. Epub 2022/01/12. doi: 10.1186/s13287-021-02689-9. PubMed PMID: 35012666; PubMed Central PMCID: PMC8751117.
• 15. Mobasheri A, Kalamegam G, Musumeci G, Batt ME. Chondrocyte and mesenchymal stem cell-based therapies for cartilage repair in osteoarthritis and related orthopaedic conditions. Maturitas. 2014;78(3):188-98. Epub 2014/05/27. doi: 10.1016/j.maturitas.2014.04.017. PubMed PMID: 24855933.
• 16. Viswanathan S, Shi Y, Galipeau J, Krampera M, Leblanc K, Martin I, et al. Mesenchymal stem versus stromal cells: International Society for Cell & Gene Therapy (ISCT®) Mesenchymal Stromal Cell committee position statement on nomenclature. Cytotherapy. 2019;21(10):1019-24. Epub 2019/09/19. doi: 10.1016/j.jcyt.2019.08.002. PubMed PMID: 31526643.
• 17. Koh YG, Kwon OR, Kim YS, Choi YJ, Tak DH. Adipose-Derived Mesenchymal Stem Cells With Microfracture Versus Microfracture Alone: 2-Year Follow-up of a Prospective Randomized Trial. Arthroscopy. 2016;32(1):97-109. Epub 2015/11/21. doi: 10.1016/j.arthro.2015.09.010. PubMed PMID: 26585585.
• 18. Arutyunyan I, Elchaninov A, Makarov A, Fatkhudinov T. Umbilical Cord as Prospective Source for Mesenchymal Stem Cell-Based Therapy. Stem Cells Int. 2016;2016:6901286. Epub 2016/09/22. doi: 10.1155/2016/6901286. PubMed PMID: 27651799; PubMed Central PMCID: PMC5019943.
• 19. Wang AT, Feng Y, Jia HH, Zhao M, Yu H. Application of mesenchymal stem cell therapy for the treatment of osteoarthritis of the knee: A concise review. World J Stem Cells. 2019;11(4):222-35. Epub 2019/05/22. doi: 10.4252/wjsc.v11.i4.222. PubMed PMID: 31110603; PubMed Central PMCID: PMC6503460.
• 20. Wang Y, Yu D, Liu Z, Zhou F, Dai J, Wu B, et al. Exosomes from embryonic mesenchymal stem cells alleviate osteoarthritis through balancing synthesis and degradation of cartilage extracellular matrix. Stem Cell Res Ther. 2017;8(1):189. Epub 2017/08/16. doi: 10.1186/s13287-017-0632-0. PubMed PMID: 28807034; PubMed Central PMCID: PMC5556343.
• 21. Freitag J, Bates D, Wickham J, Shah K, Huguenin L, Tenen A, et al. Adipose-derived mesenchymal stem cell therapy in the treatment of knee osteoarthritis: a randomized controlled trial. Regen Med. 2019;14(3):213-30. Epub 2019/02/15. doi: 10.2217/rme-2018-0161. PubMed PMID: 30762487.
• 22. Lee WS, Kim HJ, Kim KI, Kim GB, Jin W. Intra-Articular Injection of Autologous Adipose Tissue-Derived Mesenchymal Stem Cells for the Treatment of Knee Osteoarthritis: A Phase IIb, Randomized, Placebo-Controlled Clinical Trial. Stem Cells Transl Med. 2019;8(6):504-11. Epub 2019/03/06. doi: 10.1002/sctm.18-0122. PubMed PMID: 30835956; PubMed Central PMCID: PMC6525553.
• 23. Toraño EG, Bayón GF, Del Real Á, Sierra MI, García MG, Carella A, et al. Age-associated hydroxymethylation in human bone-marrow mesenchymal stem cells. J Transl Med. 2016;14(1):207. Epub 2016/07/10. doi: 10.1186/s12967-016-0966-x. PubMed PMID: 27393146; PubMed Central PMCID: PMC4938941.
• 24. Carstairs A, Genever P. Stem cell treatment for musculoskeletal disease. Curr Opin Pharmacol. 2014;16:1-6. Epub 2014/02/25. doi: 10.1016/j.coph.2014.01.005. PubMed PMID: 24561638.
• 25. Ilas DC, Churchman SM, Baboolal T, Giannoudis PV, Aderinto J, McGonagle D, et al. The simultaneous analysis of mesenchymal stem cells and early osteocytes accumulation in osteoarthritic femoral head sclerotic bone. Rheumatology (Oxford). 2019;58(10):1777-83. Epub 2019/06/06. doi: 10.1093/rheumatology/kez130. PubMed PMID: 31165896; PubMed Central PMCID: PMC6758575.
• 26. Wu X, Wang W, Meng C, Yang S, Duan D, Xu W, et al. Regulation of differentiation in trabecular bone‑derived mesenchymal stem cells by T cell activation and inflammation. Oncol Rep. 2013;30(5):2211-9. Epub 2013/08/24. doi: 10.3892/or.2013.2687. PubMed PMID: 23970332.
• 27. Neybecker P, Henrionnet C, Pape E, Mainard D, Galois L, Loeuille D, et al. In vitro and in vivo potentialities for cartilage repair from human advanced knee osteoarthritis synovial fluid-derived mesenchymal stem cells. Stem Cell Res Ther. 2018;9(1):329. Epub 2018/11/30. doi: 10.1186/s13287-018-1071-2. PubMed PMID: 30486903; PubMed Central PMCID: PMC6263063.
• 28. Turajane T, Chaveewanakorn U, Fongsarun W, Aojanepong J, Papadopoulos KI. Avoidance of Total Knee Arthroplasty in Early Osteoarthritis of the Knee with Intra-Articular Implantation of Autologous Activated Peripheral Blood Stem Cells versus Hyaluronic Acid: A Randomized Controlled Trial with Differential Effects of Growth Factor Addition. Stem Cells Int. 2017;2017:8925132. Epub 2017/10/24. doi: 10.1155/2017/8925132. PubMed PMID: 29056974; PubMed Central PMCID: PMC5625803.
• 29. Jacob G, Shimomura K, Krych AJ, Nakamura N. The Meniscus Tear: A Review of Stem Cell Therapies. Cells. 2019;9(1). Epub 2020/01/08. doi: 10.3390/cells9010092. PubMed PMID: 31905968; PubMed Central PMCID: PMC7016630.
• 30. Kern S, Eichler H, Stoeve J, Klüter H, Bieback K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells. 2006;24(5):1294-301. Epub 2006/01/18. doi: 10.1634/stemcells.2005-0342. PubMed PMID: 16410387.
• 31. Jayaram P, Ikpeama U, Rothenberg JB, Malanga GA. Bone Marrow-Derived and Adipose-Derived Mesenchymal Stem Cell Therapy in Primary Knee Osteoarthritis: A Narrative Review. Pm r. 2019;11(2):177-91. Epub 2018/07/17. doi: 10.1016/j.pmrj.2018.06.019. PubMed PMID: 30010050.
• 32. Xia P, Wang X, Lin Q, Li X. Efficacy of mesenchymal stem cells injection for the management of knee osteoarthritis: a systematic review and meta-analysis. Int Orthop. 2015;39(12):2363-72. Epub 2015/05/07. doi: 10.1007/s00264-015-2785-8. PubMed PMID: 25944079.
• 33. Lee JS, Shim DW, Kang KY, Chae DS, Lee WS. Method Categorization of Stem Cell Therapy for Degenerative Osteoarthritis of the Knee: A Review. Int J Mol Sci. 2021;22(24). Epub 2021/12/25. doi: 10.3390/ijms222413323. PubMed PMID: 34948119; PubMed Central PMCID: PMC8704290.
• 34. Cruz-Almeida Y, Sibille KT, Goodin BR, Petrov ME, Bartley EJ, Riley JL, 3rd, et al. Racial and ethnic differences in older adults with knee osteoarthritis. Arthritis Rheumatol. 2014;66(7):1800-10. Epub 2014/04/15. doi: 10.1002/art.38620. PubMed PMID: 24729357; PubMed Central PMCID: PMC4077911.
• 35. Caporali R, Cimmino MA, Sarzi-Puttini P, Scarpa R, Parazzini F, Zaninelli A, et al. Comorbid conditions in the AMICA study patients: effects on the quality of life and drug prescriptions by general practitioners and specialists. Semin Arthritis Rheum. 2005;35(1 Suppl 1):31-7. Epub 2005/08/09. doi: 10.1016/j.semarthrit.2005.02.004. PubMed PMID: 16084231.
• 36. Juhakoski R, Tenhonen S, Anttonen T, Kauppinen T, Arokoski JP. Factors affecting self-reported pain and physical function in patients with hip osteoarthritis. Arch Phys Med Rehabil. 2008;89(6):1066-73. Epub 2008/05/28. doi: 10.1016/j.apmr.2007.10.036. PubMed PMID: 18503801.
• 37. Hernigou P, Delambre J, Quiennec S, Poignard A. Human bone marrow mesenchymal stem cell injection in subchondral lesions of knee osteoarthritis: a prospective randomized study versus contralateral arthroplasty at a mean fifteen year follow-up. Int Orthop. 2021;45(2):365-73. Epub 2020/04/24. doi: 10.1007/s00264-020-04571-4. PubMed PMID: 32322943.
• 38. Bastos R, Mathias M, Andrade R, Amaral R, Schott V, Balduino A, et al. Intra-articular injection of culture-expanded mesenchymal stem cells with or without addition of platelet-rich plasma is effective in decreasing pain and symptoms in knee osteoarthritis: a controlled, double-blind clinical trial. Knee Surg Sports Traumatol Arthrosc. 2020;28(6):1989-99. Epub 2019/10/07. doi: 10.1007/s00167-019-05732-8. PubMed PMID: 31587091.
• 39. Vega A, Martín-Ferrero MA, Del Canto F, Alberca M, García V, Munar A, et al. Treatment of Knee Osteoarthritis With Allogeneic Bone Marrow Mesenchymal Stem Cells: A Randomized Controlled Trial. Transplantation. 2015;99(8):1681-90. Epub 2015/03/31. doi: 10.1097/tp.0000000000000678. PubMed PMID: 25822648.
• 40. Caplan AI. New MSC: MSCs as pericytes are Sentinels and gatekeepers. J Orthop Res. 2017;35(6):1151-9. Epub 2017/03/16. doi: 10.1002/jor.23560. PubMed PMID: 28294393.
• 41. Diekman BO, Rowland CR, Lennon DP, Caplan AI, Guilak F. Chondrogenesis of adult stem cells from adipose tissue and bone marrow: induction by growth factors and cartilage-derived matrix. Tissue Eng Part A. 2010;16(2):523-33. Epub 2009/09/01. doi: 10.1089/ten.TEA.2009.0398. PubMed PMID: 19715387; PubMed Central PMCID: PMC2813149.
• 42. Im GI. Bone marrow-derived stem/stromal cells and adipose tissue-derived stem/stromal cells: Their comparative efficacies and synergistic effects. J Biomed Mater Res A. 2017;105(9):2640-8. Epub 2017/04/19. doi: 10.1002/jbm.a.36089. PubMed PMID: 28419760.
• 43. Faustini M, Bucco M, Chlapanidas T, Lucconi G, Marazzi M, Tosca MC, et al. Nonexpanded mesenchymal stem cells for regenerative medicine: yield in stromal vascular fraction from adipose tissues. Tissue Eng Part C Methods. 2010;16(6):1515-21. Epub 2010/05/22. doi: 10.1089/ten.TEC.2010.0214. PubMed PMID: 20486782.
• 44. Cho KA, Park M, Kim YH, Woo SY, Ryu KH. RNA sequencing reveals a transcriptomic portrait of human mesenchymal stem cells from bone marrow, adipose tissue, and palatine tonsils. Sci Rep. 2017;7(1):17114. Epub 2017/12/08. doi: 10.1038/s41598-017-16788-2. PubMed PMID: 29214990; PubMed Central PMCID: PMC5719355.
• 45. Gupta PK, Chullikana A, Rengasamy M, Shetty N, Pandey V, Agarwal V, et al. Efficacy and safety of adult human bone marrow-derived, cultured, pooled, allogeneic mesenchymal stromal cells (Stempeucel®): preclinical and clinical trial in osteoarthritis of the knee joint. Arthritis Res Ther. 2016;18(1):301. Epub 2016/12/21. doi: 10.1186/s13075-016-1195-7. PubMed PMID: 27993154; PubMed Central PMCID: PMC5168586.
• 46. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8(4):315-7. Epub 2006/08/23. doi: 10.1080/14653240600855905. PubMed PMID: 16923606.
• 47. Berger DR, Aune ET, Centeno CJ, Steinmetz NJ. Cryopreserved bone marrow aspirate concentrate as a cell source for the colony-forming unit fibroblast assay. Cytotherapy. 2020;22(9):486-93. Epub 2020/06/23. doi: 10.1016/j.jcyt.2020.04.091. PubMed PMID: 32565131.
• 48. Baustian C, Hanley S, Ceredig R. Isolation, selection and culture methods to enhance clonogenicity of mouse bone marrow derived mesenchymal stromal cell precursors. Stem Cell Res Ther. 2015;6(1):151. Epub 2015/08/26. doi: 10.1186/s13287-015-0139-5. PubMed PMID: 26303631; PubMed Central PMCID: PMC4549076.
• 49. Brohem CA, de Carvalho CM, Radoski CL, Santi FC, Baptista MC, Swinka BB, et al. Comparison between fibroblasts and mesenchymal stem cells derived from dermal and adipose tissue. Int J Cosmet Sci. 2013;35(5):448-57. Epub 2013/05/09. doi: 10.1111/ics.12064. PubMed PMID: 23651429.
• 50. Bornes TD, Adesida AB, Jomha NM. Mesenchymal stem cells in the treatment of traumatic articular cartilage defects: a comprehensive review. Arthritis Res Ther. 2014;16(5):432. Epub 2015/01/22. doi: 10.1186/s13075-014-0432-1. PubMed PMID: 25606595; PubMed Central PMCID: PMC4289291.
• 51. Yin H, Wang Y, Sun Z, Sun X, Xu Y, Li P, et al. Induction of mesenchymal stem cell chondrogenic differentiation and functional cartilage microtissue formation for in vivo cartilage regeneration by cartilage extracellular matrix-derived particles. Acta Biomater. 2016;33:96-109. Epub 2016/01/24. doi: 10.1016/j.actbio.2016.01.024. PubMed PMID: 26802442.
• 52. Frith JE, Thomson B, Genever PG. Dynamic three-dimensional culture methods enhance mesenchymal stem cell properties and increase therapeutic potential. Tissue Eng Part C Methods. 2010;16(4):735-49. Epub 2009/10/09. doi: 10.1089/ten.TEC.2009.0432. PubMed PMID: 19811095.
• 53. Ramezanifard R, Kabiri M, Hanaee Ahvaz H. Effects of platelet rich plasma and chondrocyte co-culture on MSC chondrogenesis, hypertrophy and pathological responses. Excli j. 2017;16:1031-45. Epub 2017/09/14. doi: 10.17179/excli2017-453. PubMed PMID: 28900383; PubMed Central PMCID: PMC5579395.
• 54. Akgun I, Unlu MC, Erdal OA, Ogut T, Erturk M, Ovali E, et al. Matrix-induced autologous mesenchymal stem cell implantation versus matrix-induced autologous chondrocyte implantation in the treatment of chondral defects of the knee: a 2-year randomized study. Arch Orthop Trauma Surg. 2015;135(2):251-63. Epub 2014/12/31. doi: 10.1007/s00402-014-2136-z. PubMed PMID: 25548122.
• 55. Sdeek M, Sabry D, El-Sdeek H, Darweash A. Intra-articular injection of Platelet rich plasma versus Hyaluronic acid for moderate knee osteoarthritis. A prospective, double-blind randomized controlled trial on 189 patients with follow-up for three years. Acta Orthop Belg. 2021;87(4):729-34. Epub 2022/02/17. doi: 10.52628/87.4.18. PubMed PMID: 35172440.
• 56. Yurtbay A, Say F, Çinka H, Ersoy A. Multiple platelet-rich plasma injections are superior to single PRP injections or saline in osteoarthritis of the knee: the 2-year results of a randomized, double-blind, placebo-controlled clinical trial. Arch Orthop Trauma Surg. 2021. Epub 2021/10/28. doi: 10.1007/s00402-021-04230-2. PubMed PMID: 34705072.