Mesenchymal Stem Cell Therapy in Osteoarthritis Patients: A Two-Year Prospective Evaluation of Knee Joint Function
Main Article Content
Abstract
This study evaluated the functional effects of stem cell therapy on the knees of osteoarthritis patients (OP) with at 1, 2 months, and 2-year follow-up intervals. Initially, 25 patients were enrolled, but data from only 15 patients were available at the end of the two-year follow-up (approximately 40% loss to follow-up). Significant improvements in the range of motion (ROM) were observed during the early post-treatment period (1st and 2nd months). However, a slight decline in ROM was noted at the 2-year mark, which was not statistically significant in the dominant knee (p=0.06). In contrast, the non-dominant knee showed a statistically significant deterioration over the same period (p=0.04). Visual Analog Scale (VAS) scores for pain and fatigue demonstrated marked improvement in the early period post-treatment, but by the end of two years, pain had partially increased and fatigue had significantly worsened. Functional tests such as the 30-second sit-to-stand and walking distance tests showed early improvements post-treatment; however, a declining trend was observed at the two-year follow-up. Berg balance scale improved following therapy and this improvement was largely maintained at the end of two years. Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores indicated significant early improvements, and although they worsened by the end of two years, they remained significantly better than baseline. Subjective assessments revealed that patients who adhered to regular exercise achieved better clinical outcomes, while those who did not exercise reported increased pain and functional decline. Patients who did not respond to treatment underwent either knee arthroplasty or repeat stem cell therapy. Overall, stem cell therapy provided significant early clinical and functional improvements in osteoarthritic knees; however, a reduction in efficacy was observed in the long term, with deterioration noted in some parameters.
Article Details
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
2. Saghahazrati S, Ayatollahi SAM, Kobarfard F, Minaii Zang B. The Synergistic Effect of Glucagon-Like Peptide-1 and Chamomile Oil on Differentiation of Mesenchymal Stem Cells into Insulin-Producing Cells. Cell J. 2020;21(4):371-378. doi:10.22074/cellj.2020.6325
3. Somoza RA, Welter JF, Correa D, Caplan AI. Chondrogenic Differentiation of Mesenchymal Stem Cells: Challenges and Unfulfilled Expectations. Tissue Eng Part B Rev. 2014;20(6):596-608. doi:10.1089/ten.TEB.2013.0771
4. Lamo-Espinosa JM, Mora G, Blanco JF, 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. Published 2016 Aug 26. doi:10.1186/s12967-016-0998-2
5. Vangsness CT Jr, Farr J 2nd, Boyd J, Dellaero DT, Mills CR, LeRoux-Williams M. Adult Human Mesenchymal Stem Cells Delivered Via Intra-Articular Injection to the Knee Following Partial Medial Meniscectomy: A Randomized, Double-Blind, Controlled Study. J Bone Joint Surg Am. 2014;96(2):90-98. doi:10.2106/JBJS.M.00058
6. Wakitani S, Imoto K, Yamamoto T, Saito M, Murata N, Yoneda M. Human Autologous Culture Expanded Bone Marrow Mesenchymal Cell Transplantation for Repair of Cartilage Defects in Osteoarthritic Knees. Osteoarthritis Cartilage. 2002;10(3):199-206. doi:10.1053/joca.2001.0504
7. Wong KL, Lee KB, Tai BC, Law P, Lee EH, Hui JH. Injectable Cultured Bone Marrow-Derived Mesenchymal Stem Cells in Varus Knees with Cartilage Defects Undergoing High Tibial Osteotomy: A Prospective, Randomized Controlled Clinical Trial With 2 Years' Follow-Up. Arthroscopy. 2013;29(12):2020-2028. doi:10.1016/j.arthro.2013.09.074
8. 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. doi:10.1016/j.arthro.2015.09.010
9. 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):504-511. doi:10.1002/sctm.18-0122
10. Liu C, Yang Y, He G. Efficacy and Safety of Umbilical Cord-Mesenchymal Stem Cells Transplantation for Treating Osteoarthritis. Osteoarthritis and Cartilage.2017;25.
11. Pak JY. Clinical Outcomes of Human Umbilical Cord Blood Derived Mesenchymal Stem Cells Application in Knee Osteoarthritis Patients. Osteoarthritis and Cartilage.2019;27.
12. Pers YM, Rackwitz L, Ferreira R, et al. Adipose Mesenchymal Stromal Cell-Based Therapy for Severe Osteoarthritis of the Knee: A Phase I Dose-Escalation Trial. Stem Cells Transl Med. 2016;5(7):847-856. doi:10.5966/sctm.2015-0245
13. Wang Y, Jin W, Liu H, et al. Curative Effect of Human Umbilical Cord Mesenchymal Stem Cells by Intra-Articular Injection for Degenerative Knee Osteoarthritis. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2016;30(12):1472-1477. doi:10.7507/1002-1892.20160305
14. Cao M, Ou Z, Sheng R, et al. Efficacy and Safety of Mesenchymal Stem Cells in Knee Osteoarthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Stem Cell Res Ther. 2025;16(1):122. Published 2025 Mar 7. doi:10.1186/s13287-025-04252-2
15. Abdallah AN, Shamaa AA, El-Tookhy OS. Evaluation of Treatment of Experimentally Induced Canine Model of Multiple Sclerosis Using Laser Activated Non-Expanded Adipose Derived Stem Cells. Res Vet Sci. 2019;125:71-81. doi:10.1016/j.rvsc.2019.05.016
16. Fekrazad R, Sadeghi Ghuchani M, Eslaminejad MB, et al. The Effects of Combined Low Level Laser Therapy and Mesenchymal Stem Cells on Bone Regeneration in Rabbit Calvarial Defects. J Photochem Photobiol B. 2015;151:180-185. doi:10.1016/j.jphotobiol.2015.08.002
17. Gonçalves ED, Souza PS, Lieberknecht V, et al. Low-Level Laser Therapy Ameliorates Disease Progression in a Mouse Model of Multiple Sclerosis. Autoimmunity. 2016;49(2):132-142. doi:10.3109/08916934.2015.1124425
18. Kim J, Kim EH, Lee K, et al. Low-Level Laser Irradiation Improves Motor Recovery After Contusive Spinal Cord Injury in Rats. Tissue Eng Regen Med. 2017;14(1):57-64. Published 2017 Jan 17. doi:10.1007/s13770-016-0003-4
19. Pinheiro CCG, de Pinho MC, Aranha AC, Fregnani E, Bueno DF. Low Power Laser Therapy: A Strategy to Promote the Osteogenic Differentiation of Deciduous Dental Pulp Stem Cells from Cleft Lip and Palate Patients. Tissue Eng Part A. 2018;24(7-8):569-575. doi:10.1089/ten.TEA.2017.0115
20. Shingyochi Y, Kanazawa S, Tajima S, Tanaka R, Mizuno H, Tobita M. A Low-Level Carbon Dioxide Laser Promotes Fibroblast Proliferation and Migration through Activation of Akt, ERK, and JNK. PLoS One. 2017;12(1):e0168937. Published 2017 Jan 3. doi:10.1371/journal.pone.0168937
21. So KF, Leung MC, Cui Q. Effects of Low Level Laser Treatment on The Survival of Axotomized Retinal Ganglion Cells in Adult Hamsters. Neural Regen Res. 2014;9(21):1863-1869. doi:10.4103/1673-5374. 145337
22. Huang W, Li Q, Zhao F. Mesenchymal Stem Cells Combined Therapies in OA: Impact on Clinical Outcomes. Osteoarthritis Cartilage. 2022;30(2):215-224.
23. Song J, Lee M, Kim H. Meta-Analysis of Mscs in Osteoarthritis: Limitations and Clinical Evidence. Journal Of Orthopedic Research.2020;3(5):1123-1131.
24. Xie Z, Wang L, Zhang Y. Efficacy of Mesenchymal Stem Cells in OA Treatment: A Meta-analysis. Stem Cell Res Ther.2021;1(12):100.
25. Certel Ö, Menekseoglu N, Pündük Z. An Examination of the Effects of Stem Cell Therapy on Knee Functionality in Patients Diagnosed with Knee Osteoarthritis. Rev Gest Soc Ambient. 2025;19(4):1-10. doi:10.24857/rgsa.v19n4-061
26. Kim HJ, et al. Large-Scale RCT of MSC Therapy in OA. Arthritis Rheumatol. 2023;75(2):220-230.
27. Song Y, et al. Efficacy of MSC From Different Sources in OA: A Meta-analysis. Stem Cell Research & Therapy.2020;11(1):310.
28. Maheshwer B. Effects of MSC on Cartilage Volume and Quality. Cartilage.2023;14(1):56-57.
29. Xie L, et al. MSC Therapy Outcomes in OA: Systematic Review. Journal of Clinical Medicine.2021;10(12): 2678.
30. Jeyaraman MM, et al. Meta-analysis of MSC therapy in OA. J Orthop Res. 2022;40(6):1234-1245.
31. Shanahan EM et al. Pain Management in OA. Pain Medicine.2021;22(8):1800-1810.