Intra-articular injection of mesenchymal stem cells for clinical outcomes and cartilage repair in osteoarthritis of the knee: a meta-analysis of randomized controlled trials
Mesenchymal stem cells (MSCs) have gained popularity for articular cartilage repair. However, efficacy of intra-articular MSCs in osteoarthritis remains unclear. In the setting of a meta-analysis of randomized controlled trials (RCTs), we aimed to investigate the efficacy of intra-articular MSCs on clinical outcomes and cartilage repair in patients with knee osteoarthritis.
Materials and methods
PubMed, EMBASE, Cochrane Library, CINAHL, and Scopus were searched from inception to March 31, 2017. This study included RCTs using cell population containing MSCs for treatment of knee osteoarthritis. The quality was assessed by Cochrane Collaboration`s risk of bias tool. For meta-analysis, data on clinical outcomes measured by visual analog scale (VAS), Lysholm score, WOMAC and data on cartilage repair measured by MOCART and WORMS were extracted. In studies with several cell concentrations, outcomes of recommended concentration were used mainly to ensure robustness.
A total of five RCTs (220 patients) were included. Two studies were deemed to have low risk of bias. In pooled analysis, there was significant difference in VAS score (mean difference [MD], − 9.2; 95% CI: − 17.21, − 1.20) and Lysholm score (MD, 8.70; 95% CI 0.06, 17.34), but not WOMAC (MD, − 7.44; 95% CI − 20.38, 5.50). In cumulative functional analysis using Lysholm score and WOMAC in recommended concentration, there was a significant improvement (standard mean difference [SMD], 0.53; 95% CI 0.13, 0.94) after treatment. In cartilage repair assessed by MRI, there was no significant difference (SMD, 0.53; 95% CI− 0.28, 1.34).
This meta-analysis demonstrated that intra-articular MSCs have a limited evidence in pain relief and functional improvement in knee osteoarthritis. While MSCs may result in favorable clinical outcomes with a recommended concentration, use of concomitant treatment should be considered. In addition, current evidence does not support the use of intra-articular MSCs for improving cartilage repair in knee osteoarthritis.
Level of evidence
Systematic review of Level-II studies.
KeywordsOsteoarthritis Mesenchymal stem cells Clinical outcome Cartilage repair Meta-analysis
This study was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant number: HI14C3484). The funding sources were not involved in the study design, collection, analysis or interpretation of the data, writing of the manuscript, or in the decision to submit the manuscript for publication.
Compliance with ethical standards
Conflict of interest
All authors declare that they have no conflict of interest.
This article does not contain any studies with human participants performed by any of the authors.
For this type of study, formal consent is not required.
- 3.Bruyere O, Cooper C, Pelletier JP, Maheu E, Rannou F, Branco J, Luisa Brandi M, Kanis JA, Altman RD, Hochberg MC, Martel-Pelletier J, Reginster JY (2016) A consensus statement on the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) algorithm for the management of knee osteoarthritis-from evidence-based medicine to the real-life setting. Semin Arthritis Rheum 45(4 Suppl):S3–S11CrossRefGoogle Scholar
- 8.Jones EA, Crawford A, English A, Henshaw K, Mundy J, Corscadden D, Chapman T, Emery P, Hatton P, McGonagle D (2008) Synovial fluid mesenchymal stem cells in health and early osteoarthritis: detection and functional evaluation at the single-cell level. Arthritis Rheum 58(6):1731–1740CrossRefGoogle Scholar
- 14.Rodriguez-Merchan EC (2014) Intra-articular injections of mesenchymal stem cells for knee osteoarthritis. Am J Orthop 43(12):E282–E291. (Belle Mead NJ) Google Scholar
- 17.Bourin P, Bunnell BA, Casteilla L, Dominici M, Katz AJ, March KL, Redl H, Rubin JP, Yoshimura K, Gimble JM (2013) Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: a joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT). Cytotherapy 15(6):641–648CrossRefGoogle Scholar
- 18.Gupta PK, Chullikana A, Rengasamy M, Shetty N, Pandey V, Agarwal V, Wagh SY, Vellotare PK, Damodaran D, Viswanathan P, Thej C, Balasubramanian S, Majumdar AS (2016) Efficacy and safety of adult human bone marrow-derived, cultured, pooled, allogeneic mesenchymal stromal cells (Stempeucel(R)): preclinical and clinical trial in osteoarthritis of the knee joint. Arthr Res Ther 18(1):301CrossRefGoogle Scholar
- 19.Lamo-Espinosa JM, Mora G, Blanco JF, Granero-Molto F, Nunez-Cordoba JM, Sanchez-Echenique C, Bondia JM, Aquerreta JD, Andreu EJ, Ornilla E, Villaron EM, Valenti-Azcarate A, Sanchez-Guijo F, Del Canizo MC, Valenti-Nin JR, Prosper F (2016) 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 14(1):246CrossRefGoogle Scholar
- 20.Wong KL, Lee KB, Tai BC, Law P, Lee EH, Hui JH (2013) 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 29(12):2020–2028CrossRefGoogle Scholar
- 23.Vega A, Martin-Ferrero MA, Del Canto F, Alberca M, Garcia V, Munar A, Orozco L, Soler R, Fuertes JJ, Huguet M, Sanchez A, Garcia-Sancho J (2015) Treatment of knee osteoarthritis with allogeneic bone marrow mesenchymal stem cells: a randomized controlled trial. Transplantation 99(8):1681–1690CrossRefGoogle Scholar
- 27.Schuster P, Schulz M, Mayer P, Schlumberger M, Immendoerfer M, Richter J (2015) Open-wedge high tibial osteotomy and combined abrasion/microfracture in severe medial osteoarthritis and varus malalignment: 5-year results and arthroscopic findings after 2 years. Arthroscopy 31(7):1279–1288CrossRefGoogle Scholar
- 28.Park YB, Ha CW, Lee CH, Yoon YC, Park YG (2017) Cartilage regeneration in osteoarthritic patients by a composite of allogeneic umbilical cord blood-derived mesenchymal stem cells and hyaluronate hydrogel: results from a clinical trial for safety and proof-of-concept with 7 years of extended follow-up. Stem Cells Transl Med 6(2):613–621CrossRefGoogle Scholar
- 36.Park YB, Ha CW, Kim JA, Rhim JH, Park YG, Chung JY, Lee HJ (2016) Effect of transplanting various concentrations of a composite of human umbilical cord blood-derived mesenchymal stem cells and hyaluronic acid hydrogel on articular cartilage repair in a rabbit model. PLoS One 11(11):e0165446CrossRefGoogle Scholar