International Orthopaedics

, Volume 39, Issue 12, pp 2363–2372 | Cite as

Efficacy of mesenchymal stem cells injection for the management of knee osteoarthritis: a systematic review and meta-analysis

  • Peng Xia
  • Xiaoju Wang
  • Qiang Lin
  • Xueping Li
Review Article



The purpose of this study was to access the efficacy of mesenchymal stem cells (MSCs) injection in the treatment of knee osteoarthritis (OA).


Studies were identified from databases (Pubmed, Embase, Cochrane Library, Biosis Previews,, CBMdisc) searched to December 2014 using a battery of keywords. We included randomized controlled and controlled clinical trials of people with knee OA comparing the outcomes of pain and function for those receiving MSCs injection with those receiving no MSCs injection. Two reviewers independently selected studies, extracted relevant data and assessed study quality. Data were pooled and meta-analyses were performed.


Seven randomized controlled and controlled clinical trials, studying a total of 314 participants with a diagnosis of knee OA were included. Overall, MSCs injection has no significant effect on pain [weighted mean difference (WMD) (95 % confidence interval (CI)) [−1.33(−3.08, 0.41), P = 0.13], and tends to improve self-reported physical function [standardized mean difference (SMD) (CI) = 2.35(0.92, 3.77), P = 0.001] at the last follow-up. But results from two high quality trials (94 patients) show a positive effect of MSCs injection on pain [WMD(CI) = −0.49 (−0.79, −0.19), P = 0.001]. Heterogeneity observed between studies regarding the effect of MSCs injection on pain and function was explained by the difference of follow-up time, outcome measures, control group, the source and dose of MSCs. The quality of evidence supporting these effect estimates was rated as low.


MSCs injection could be potentially efficacious for decreasing pain and may improve physical function in patients with knee OA. The findings of this review should be confirmed using methodologically rigorous and adequately powered clinical trials.


Mesenchymal stem cells (MSCs) Osteoarthritis (OA) Knee Meta-analysis 



We thank the National Science Foundation of China (Grant # 81272151) for financial support.


  1. 1.
    Pop T, Szczygielska D, Druzbicki M (2007)Epidemiology and cost of conservative treatment of patients with degenerative joint disease of the hip and knee. Ortop Traumatol Rehabil 9:405–412PubMedGoogle Scholar
  2. 2.
    Quintana JM, Arostegui I, Escobar A et al (2008)Prevalence of knee and hip osteoarthritis and the appropriateness of joint replacement in an older population. Arch Intern Med 168:1576–1584CrossRefPubMedGoogle Scholar
  3. 3.
    Zhang Y, Jordan JM (2008)Epidemiology of osteoarthritis. Rheum Dis Clin North Am 34:515–529PubMedCentralCrossRefPubMedGoogle Scholar
  4. 4.
    Simon LS (1999)Osteoarthritis. Curr Rheumatol Rep 1:45–7CrossRefPubMedGoogle Scholar
  5. 5.
    ACR (2000)American College of Rheumatology Subcommittee on osteoarthritis guidelines. Recommendations for the medical management of osteoarthritis of the hip and knee. 2000 Update. Arthritis Rheum 43:1905–1915CrossRefGoogle Scholar
  6. 6.
    Felson DT, Zhang Y, Anthony JM et al (1992)Weight loss reduces the risk for symptomatic knee osteoarthritis in woman. The Framingham Study. Ann Intern Med 116:535–539CrossRefPubMedGoogle Scholar
  7. 7.
    Zang W, Moskowitz RW, Nuki G et al (2008)OARSI recommendations for the management of hip and knee osteoarthritis. Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthritis Cartilage 16:137–162CrossRefGoogle Scholar
  8. 8.
    Bellamy N, Campbell J, Robinson V et al (2006)Intraarticular corticosteroid for treatment of osteoarthritis of the knee. Cochrane Database Sys Rev 19:CD005328Google Scholar
  9. 9.
    Hepper CT, Halvorson JJ, Duncan ST et al (2009)The efficacy and duration of intra-articularcorticosteroid injection for knee osteoarthritis: a systematic review of level I studies. J Am Acad Orthop Surg 17:638–646PubMedGoogle Scholar
  10. 10.
    Alhadlaq A, Mao JJ (2004)Mesenchymal stem cells: isolation and therapeutics. Stem Cells Dev 13:436–448CrossRefPubMedGoogle Scholar
  11. 11.
    Wakitani S, Okabe T, Horibe S et al (2010)Safety of autologous bone marrow-derivedmesenchymal stem cell transplantation for cartilage repair in 41 patients with 45 joints followed for up to 11 years and 5 months. J Tissue Eng Regen Med 5:146–150CrossRefGoogle Scholar
  12. 12.
    Wakitani S, Nawata M, Tensho K et al (2007)Repair of articular cartilage defects in the patello-femoraljoint with autologous bone marrow mesenchymal cell transplantation: three case reports involving nine defects in five knees. J Tissue Eng Regen Med 1:74–79CrossRefPubMedGoogle Scholar
  13. 13.
    Koh YG, Jo SB, Kwon OR et al (2013)Mesenchymal stem cell injections improve symptoms of knee osteoarthritis. Arthroscopy 29:748–755CrossRefPubMedGoogle Scholar
  14. 14.
    Davatchi F, Abdollahi BS, Mohyeddin M et al (2011)Mesenchymal stem cell therapy for knee osteoarthritis. Preliminary report of four patients. Int J Rheum Dis 14:211–215CrossRefPubMedGoogle Scholar
  15. 15.
    Jo CH, Lee YG, Shin WH et al (2014)Intra-articularinjection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a proof-of-conceptclinical trial. Stem Cells 32:1254–1266Google Scholar
  16. 16.
    Banares R, Albillos A, Rincon D et al (2002)Endoscopic treatment versus endoscopic plus pharmacologic treatment for acute variceal bleeding: a meta-analysis. Hepatology 35:609–615CrossRefPubMedGoogle Scholar
  17. 17.
    Jüni P, Reichenbach S, Dieppe P (2006)Osteoarthritis: rational approach to treating the individual. Best Pract Res Clin Rheumatol 20:721–740CrossRefPubMedGoogle Scholar
  18. 18.
    Higgins JPT, Thompson SG, Deeks JJ et al (2003)Measuring inconsistency in meta-analyses. BMJ 327:557–560PubMedCentralCrossRefPubMedGoogle Scholar
  19. 19.
    Centeno CJ, Freeman MD (2014)Percutaneous injection of autologous, culture-expandedmesenchymal stem cells into carpometacarpal hand joints: a case series with an untreated comparison group. Wien Med Wochenschr 164:83–87CrossRefPubMedGoogle Scholar
  20. 20.
    Chen K, Man C, Zhang B et al (2013)Effect of in vitro chondrogenic differentiation of autologous mesenchymal stem cells on cartilage and subchondral cancellous bone repair in osteoarthritis of temporomandibular joint. Int J Oral Maxillofac Surg 42:240–248CrossRefPubMedGoogle Scholar
  21. 21.
    Yang XH, Peng L, Liu YS et al (2013)Bone marrow mesenchymal stem cell transplantation for the treatment of temporomandibular joint osteoarthrosis. Chin J Tissue Eng Res 17:3488–3494Google Scholar
  22. 22.
    Centeno CJ, Busse D, Kisiday J et al (2008)Increased knee cartilage volume in degenerative joint disease using percutaneously implanted, autologous mesenchymal stem cells. Pain Physician 11:343PubMedGoogle Scholar
  23. 23.
    Gupta ED, Nayyer N, Chin SP et al (2010)Clinical safety and efficacy of autologous bone marrow mesenchymal stem cell injection for the treatment of severe osteoarthritis. Int J Rheum Dis 13:42CrossRefGoogle Scholar
  24. 24.
    Slynarski K, Deszczynski J, Karpinski J (2006)Fresh bone marrow and periosteum transplantation for cartilage defects of the knee. Transplant Proc 38:318–319CrossRefPubMedGoogle Scholar
  25. 25.
    Orozco L, Munar A, Soler R et al (2013)Treatment of knee osteoarthritis with autologous mesenchymal stem cells: a pilot study. Transplantation 95:1535–1541CrossRefPubMedGoogle Scholar
  26. 26.
    Orozco L, Munar A, Soler R et al (2014)Treatment of knee osteoarthritis with autologous mesenchymal stem cells: two-yearfollow-up results. Transplantation 97:e66–e68CrossRefPubMedGoogle Scholar
  27. 27.
    Varma HS, Dadarya B, Vidyarthi A (2010)The new avenues in the management of osteo-arthritisof knee–stem cells. J Indian Med Assoc 108:583–585PubMedGoogle Scholar
  28. 28.
    Wong KL, Lee KBL, Tai BC et al (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: J Arthrosc Relat Surg 29:2020–2028CrossRefGoogle Scholar
  29. 29.
    Koh Y, Choi Y (2012)Infrapatellar fat pad-derivedmesenchymal stem cell therapy for knee osteoarthritis. Knee 19:902–907CrossRefPubMedGoogle Scholar
  30. 30.
    Koh YG, Kwon OR, Kim YS et al (2014)Comparative outcomes of open-wedgehigh tibial osteotomy with platelet-richplasma alone or in combination with mesenchymal stem cell treatment: a prospective study. Arthroscopy 30:1453–1460CrossRefPubMedGoogle Scholar
  31. 31.
    Orozco L, Munar A, Soler R et al. (2014)Treatment of knee osteoarthritis with allogenic mesenchymal stem cells., Identifier: NCT01586312
  32. 32.
    Gan F, Tang C, Guo D et al (2014)The treatment of mesenchymal stem cell transplantation for knee osteoarthritis: a clinical observation study. Modern Diagn Treat 3512–13 (Article in Chinese)Google Scholar
  33. 33.
    Tan Y, Jiang M, Yu H et al (2013)Therapeutic effect of arthroscopy combined with autologous bone marrow stem cell grafting on knee osteoarthritis. J Tradit Chin Orthop Traumatol 35–38 (Article in Chinese)Google Scholar
  34. 34.
    Gómez-Barrena E, Solá CA, Bunu CP (2014)Regulatory authorities and orthopaedic clinical trials on expanded mesenchymal stem cells. Int Orthop 38:1803–1809CrossRefPubMedGoogle Scholar
  35. 35.
    Hernigou P (2015)Bone transplantation and tissue engineering, part IV. Mesenchymal stem cells: history in orthopedic surgery from Cohnheim and Goujon to the Nobel Prize of Yamanaka. Int Orthop 39:807–817CrossRefPubMedGoogle Scholar
  36. 36.
    Wang X, Wang Y, Gou W et al (2013)Role of mesenchymal stem cells in bone regeneration and fracture repair: a review. Int Orthop 37:2491–2498PubMedCentralCrossRefPubMedGoogle Scholar
  37. 37.
    Jang S-J, Kim J-D, Cha S-S(2013)Platelet-richplasma (PRP)injections as an effective treatment for early osteoarthritis. Eur J Orthop Surg Traumatol 23:573–580Google Scholar
  38. 38.
    Halpern B, Chaudhury S, Rodeo SA et al (2013)Clinical and MRI outcomes after platelet-richplasma treatment for knee osteoarthritis. Clin J Sport Med 23:238–239CrossRefPubMedGoogle Scholar
  39. 39.
    Gobbi A, Karnatzikos G, Mahajan V et al (2012)Platelet-richplasma treatment in symptomatic patients with knee osteoarthritis: preliminary results in a group of active patients. Sports Health 4:162–172Google Scholar
  40. 40.
    Sampson S, Reed M, Silvers H et al (2010)Injection of platelet-richplasma in patients with primary and secondary knee osteoarthritis: a pilot study. Am J Phys Med Rehabil 89:961–969CrossRefPubMedGoogle Scholar
  41. 41.
    Filardo G, Kon E, Buda R et al (2011)Platelet-richplasma intra-articularknee injections for the treatment of degenerative cartilage lesions and osteoarthritis. Knee Surg Sports Traumatol Arthosc 19:528–535Google Scholar

Copyright information

© SICOT aisbl 2015

Authors and Affiliations

  1. 1.Department of Rehabilitation Medicine, Nanjing First HospitalNanjing Medical UniversityNanjingChina

Personalised recommendations