Therapeutic Modality of Mesenchymal Stem Cells for Moderate to Severe Knee Osteoarthtritis: A Systematic Review
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Background: Osteoarthritis (OA) is a chronic degenerative joint disease that commonly affects weight-bearing joints, such as the knee. A potential treatment is the intra-articular injection of mesenchymal stem cells (MSCs), which may stimulate joint tissue regeneration, cartilage formation, and angiogenesis. This systematic review aimed to evaluate the efficacy and safety of MSC therapy in moderate-to-severe knee OA.
Methods: Literature searches were conducted using PubMed, Science Direct, Taylor and Francis, Google Scholar, Springer Link, Wiley, and the Garuda Portal. From the 644 identified articles, only seven randomized controlled trials published within the last 10 years met the inclusion criteria.
Results: Five of the seven studies demonstrated significant reductions in pain based on Visual Analog Scale (VAS) scores following MSC injections. Four studies reported significant improvements in WOMAC scores, whereas one study showed no notable change. Adverse effects noted after injections included joint swelling, contusions, postprocedural hematomas, mild effusion, and injection site pain.
Conclusions: Intra-articular MSC therapy shows potential for reducing pain and improving joint function in moderate-to-severe knee OA. Improvements in VAS and WOMAC scores suggest clinical benefits that can last up to 12–48 months post-treatment. MSC injections may be considered as a causal therapy in addition to symptomatic treatments, such as analgesics, to enhance patient quality of life.
Coaccioli S, Sarzi-Puttini P, Zis P, Rinonapoli G, Varrassi G. Osteoarthritis: New Insight on its Pathophysiology J Clin Med 2022;11(20):1–12.
Roux CH, Ferrero S. Epidemiology of osteoarthritis. Revue du Rhumatisme (Edition Francaise) 2024;91(4):496–502.
El-Tawil S, Arendt E, Parker D. Position statement: the epidemiology, pathogenesis and risk factors of osteoarthritis of the knee. J ISAKOS 2016;1(4):219–228.
Kohn MD, Sassoon AA, Fernando ND. Classifications in Brief: Kellgren-Lawrence Classification of Osteoarthritis. Clin Orthop Relat Res 2016; 474(8):1886–1893.
Pers YM ., Ruiz M, Noël D, Jorgensen C. Mesenchymal stem cells for the management of inflammation in osteoarthritis: state of the art and perspectives. Osteoarthritis Cartilage 2015 Nov;23(11):2027–35.
Tong L, Yu H, Huang X, Shen J, Xiao G, Chen L et al. Current understanding of osteoarthritis pathogenesis and relevant new approaches. Bone Res 2022;10(1):60.
Mora JC, Przkora R, Cruz-Almeida Y. Knee osteoarthritis: Pathophysiology and current treatment modalities. J Pain Res 2018;11:2189–2196.
Mandl LA. Osteoarthritis year in review 2018: clinical. Osteoarthritis Cartilage 2019;27(3):359–364.
Giorgino R, Albano D, Fusco S, Peretti GM, Mangiavini L, Messina C. Knee Osteoarthritis: Epidemiology, Pathogenesis, and Mesenchymal Stem Cells: What Else Is New? An Update. Int J Mol Sci 2023;24(7).
Geng R, Li J, Yu C, Zhang C, Chen F, Chen J et al. Knee osteoarthritis: Current status and research progress in treatment (Review). Exp Ther Med 2023;26(4):1–11.
Mautner K, Gottschalk M, Boden SD, Akard A, Bae WC, Black L, et al. Cell-based versus corticosteroid injections for knee pain in osteoarthritis: a randomized phase 3 trial. Nat Med 2023;29(12):3120–6.
Shadmanfar S, Labibzadeh N, Emadedin M, Jaroughi N, Azimian V, Mardpour S, et al. Intra-articular implantation of autologous bone marrow–derived mesenchymal stromal cells to treat knee osteoarthritis: a randomized, triple-blind, placebo-controlled phase 1/2 clinical trial. Cytotherapy 2018;20(10):1238–46.
Lamo-Espinosa JM, Mora G, Blanco JF, Granero-Moltó F, Núñez-Córdoba JM, López-Elío S, et al. Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: long-term follow-up of a multicenter randomized controlled clinical trial (phase I/II). J Transl Med 2018;16:213.
Lamo-Espinosa JM, Mora G, Blanco JF, Granero-Moltó F, Núñez-Córdoba JM, López-Elío S, et al. Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: multicenter randomized controlled clinical trial (phase I/II). J Transl Med 2016;14(1):246.
Lamo-Espinosa JM, Blanco JF, Sánchez M, García V, Fernández-García P, Andreu E, et al. Phase II multicenter randomized controlled clinical trial on the efficacy of intra-articular injection of autologous bone marrow mesenchymal stem cells with platelet rich plasma for the treatment of knee osteoarthritis. J Transl Med 2020;18(1):356.
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.
Khalifeh SS, Forogh B, Ahmadbeigi N, Hadizadeh Kharazi H, Fallahzadeh K, Kashani L, et al. Safety and efficacy of allogenic placental mesenchymal stem cells for treating knee osteoarthritis: a pilot study. Cytotherapy 2019 Jan;21(1):54–63.
Zakrzewski W, Dobrzyński M, Szymonowicz M, Rybak Z. Stem cells: past, present, and future. Stem Cell Res Ther 2019;68(10).
Peng Y, Jiang H, Zuo HD. Factors affecting osteogenesis and chondrogenic differentiation of mesenchymal stem cells in osteoarthritis. World J Stem Cells 2023;15(6):548–60.
Kim K Il, Lee MC, Lee JH, Moon YW, Lee WS, Lee HJ, et al. Clinical Efficacy and Safety of the Intra-articular Injection of Autologous Adipose-Derived Mesenchymal Stem Cells for Knee Osteoarthritis: A Phase III, Randomized, Double-Blind, Placebo-Controlled Trial. Am J Sports Med 2023;51(9):2243–53.
Kyriakidis T, Pitsilos C, Iosifidou M, Tzaveas A, Gigis I, Ditsios K, et al. Stem cells for the treatment of early to moderate osteoarthritis of the knee: a systematic review. J Exp Orthop 2023;10(1):1–10.
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