Efficacy and safety of mesenchymal stem cell therapies for knee cartilage injuries: a systematic review
DOI:
https://doi.org/10.33448/rsd-v14i9.49599Keywords:
Articular Cartilage, Cell Therapy, Knee Injuries, Mesenchymal Stem Cells, Tissue Regeneration, Review.Abstract
Introduction: Stem cell therapies have emerged as an innovative and promising alternative for the treatment of knee cartilage injuries, aiming to promote tissue regeneration and delay the need for arthroplasty. Objective: To assess the efficacy and safety of stem cell therapies, particularly mesenchymal and autologous stem cells, in the treatment of knee cartilage injuries in adults. Methods: This systematic review followed the PRISMA guidelines and was registered in PROSPERO (CRD420251028539). Clinical studies published between 2015 and 2025 on mesenchymal stem cell (MSC) therapy in adults with knee cartilage injuries were included. A comprehensive search was conducted in PubMed, LILACS, and SciELO. Study selection, data extraction, and risk of bias assessment were performed independently by reviewers. Results: The nine studies analyzed indicate that the use of MSCs, derived from bone marrow or adipose tissue, shows positive effects in the treatment of knee osteoarthritis. The main outcomes included improvements in pain, joint function, and quality of life, with a low risk of adverse events. However, the heterogeneity of methodological designs, cell types, and application protocols prevents meta-analysis and limits the generalizability of the findings. While promising, the results highlight the need for more controlled studies with larger sample sizes and longer follow-up periods to validate the clinical efficacy and safety of MSCs. Conclusions: Mesenchymal stem cell therapies appear to be a promising option for knee osteoarthritis, with observed clinical benefits. Nevertheless, more standardized studies are needed to confirm their efficacy and establish safe application guidelines.
References
Buckwalter, J. A. & Mankin, H. J. (1998). Articular cartilage: tissue design and chondrocyte-matrix interactions. Instr Course Lect. 47, 477–86.
Chahla, J. et al. (2020). Defining the minimal clinically important difference and patient acceptable symptom state for microfracture of the knee: a psychometric analysis at short-term follow-up. The American Journal of Sports Medicine. 48(4), 876–83. DOI: https://doi.org/10.1177/0363546520903279.
Chung, Y. W. et al. (2021)Allogeneic umbilical cord blood-derived mesenchymal stem cells combined with high tibial osteotomy: a retrospective study on safety and early results. International orthopaedics. 45(2), 481. DOI: https://doi.org/10.1007/s00264-020-04852-y.
de Windt, T. S., et al. (2017). Allogeneic MSCs and Recycled Autologous Chondrons Mixed in a One-Stage Cartilage Cell Transplantion: A First-in-Man Trial in 35 Patients. Stem cells (Dayton, Ohio). 35(8), 1984. https://doi.org/10.1002/stem.2657.
Gobbi, A. & Whyte, G. P. (2016). One-stage cartilage repair using a hyaluronic acid-based scaffold with activated bone marrow-derived mesenchymal stem cells compared with microfracture: five-year follow-up. American Journal of Sports Medicine. 44(11), 2846–54. DOI: https://doi.org/10.1177/0363546516656179.
Hoburg, A. et al. (2023). Sustained superiority in KOOS subscores after matrix-associated chondrocyte implantation using spheroids compared to microfracture. Knee Surgery, Sports Traumatology, Arthroscopy. 31(6), 2482–93. DOI: https://doi.org/10.1007/s00167-022-07194-x.
Kraeutler, M. J. et al. (2018). Microfracture versus autologous chondrocyte implantation for articular cartilage lesions in the knee: a systematic review of 5-year outcomes. The American Journal of Sports Medicine. 46(4), 995–9. DOI: https://doi.org/10.1177/0363546517701912.
Liu, H. et al. (2022). Mesenchymal stem cells in the treatment of osteoarthritis: new insights and perspectives. Stem Cell Research & Therapy. 13(1), 132,. DOI: https://doi.org/10.1186/s13287-022-02804-6 .
Liu, J. N. et al. (2019). Establishing clinically significant outcomes after meniscal allograft transplantation. Orthopaedic Journal of Sports Medicine. 7(1). DOI: https://doi.org/10.1177/2325967118818462.
Maheshwer, B. et al. (2021). Establishing the minimal clinically important difference and patient-acceptable symptomatic state after arthroscopic meniscal repair and associated variables for achievement. Arthroscopy. 37(12), 3479–86. DOI: https://doi.org/10.1016/j.arthro.2021.04.058.
Min, B. H. et al. (2017). Development and efficacy testing of a “hollow awl” that leads to patent bone marrow channels and greater mesenchymal stem cell mobilization during bone marrow stimulation cartilage repair surgery. Arthroscopy. 33(11), 2045–51. DOI: https://doi.org/10.1016/j.arthro.2017.06.022.
Page, M. J. et al. (2021). The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 372(71). DOI: https://doi.org/10.1136/bmj.n71.
Pereira, A. S., et al. (2018). Metodologia da pesquisa científica. [e-book]. Ed. UAB/NTE/UFSM.
Qiao, Z. et al. (2020). Human adipose-derived mesenchymal progenitor cells plus microfracture and hyaluronic acid for cartilage repair: a Phase IIa trial. Regenerative Medicine. 15(1), 1193–214. DOI: https://doi.org/10.2217/rme-2019-0068.
Sadri, B. et al. (2023). Cartilage regeneration and inflammation modulation in knee osteoarthritis following injection of allogeneic adipose-derived mesenchymal stromal cells: a phase II, triple-blinded, placebo controlled, randomized trial. Stem Cell Research & Therapy. 14(1), 162. DOI: https://doi.org/10.1186/s13287-023-03359-8.
Saris, T. F. F. et al. (2021). Five-year outcome of 1-stage cell-based cartilage repair using recycled autologous chondrons and allogenic mesenchymal stromal cells: a first-in-human clinical trial. American Journal of Sports Medicine. 49(4), 941–7. DOI: https://doi.org/10.1177/0363546520988069.
Shin, S. et al. (2021). Comparative proteomic analysis of the mesenchymal stem cells secretome from adipose, bone marrow, placenta and Wharton's jelly. International Journal of Molecular Sciences. 22(2), 845. DOI: https://doi.org/10.3390/ijms22020845.
Snyder, H. (2019). Literature Review as a Research Methodology: An Overview and Guidelines. Journal of Business Research, 104, 333-339. https://doi.org/10.1016/j.jbusres.2019.07.039.
Soler, R. et al. (2016). Final results of a phase I-II trial using ex vivo expanded autologous mesenchymal stromal cells for the treatment of osteoarthritis of the knee confirming safety and suggesting cartilage regeneration. Knee. 23(4), 647–54. DOI: https://doi.org/10.1016/j.knee.2015.08.013.
Teixeira, F. G. et al. (2016). Modulation of the mesenchymal stem cell secretome using computer-controlled bioreactors: impact on neuronal cell proliferation, survival and differentiation. Scientific Reports. 6, 27791. DOI: https://doi.org/10.1038/srep27791.
Vega, A. et al. (2015). Treatment of knee osteoarthritis with allogeneic bone marrow mesenchymal stem cells: a randomized controlled trial. Transplantation. 99(8), 1681–90. DOI: https://doi.org/10.1097/TP.0000000000000678.
Yoon, K. H., Lee, J. & Park, J. Y. (2024). Costal chondrocyte-derived pellet-type autologous chondrocyte implantation versus microfracture for repair of articular cartilage defects: a prospective randomized trial. The American Journal of Sports Medicine. 52(2), 362–7. DOI: https://doi.org/10.1177/03635465231222797.
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