Skip to main content

Mesenchymal stem cell-based treatment for cartilage defects in osteoarthritis


Osteoarthritis (OA) is a common disorder and the restoration of the diseased articular cartilage in patients with OA is still a challenge for researchers and clinicians. Currently, a variety of experimental strategies have investigated whether mesenchymal stem cells (MSCs) instead of chondrocytes can be used for the regeneration and maintenance of articular cartilage in OA. MSCs can modulate the immune response of individuals and positively influence the microenvironment of the stem cells already present in the diseased tissue. Through direct cell–cell interaction or the secretion of various factors, MSCs can initiate endogenous regenerative activities in the OA joint. Targeted gene-modified MSC-based therapy might further enhance the cartilage regeneration in OA. Conventionally, delivery of MSCs was attained by graft of engineered constructs derived from cell-seeded scaffolds. However, intra-articular MSCs transplantation without scaffolds is a more attractive option for OA treatment. This article briefly summarizes the current knowledge about MSC-based therapy for prevention or treatment of OA, discussing the direct intra-articular injection of MSCs for the treatment of OA in animal models and in clinical applications, as well as potential future strategies for OA treatment.

This is a preview of subscription content, access via your institution.


  1. 1.

    Wieland HA, Michaelis M, Kirschbaum BJ, Rudolphi KA (2005) Osteoarthritis—an untreatable disease? Nat Rev Drug Discov 4:331–344

    PubMed  Article  CAS  Google Scholar 

  2. 2.

    Buckwalter JA, Saltzman C, Brown T (2004) The impact of osteoarthritis: implications for research. Clin Orthop Relat Res 427:S6–S15

    PubMed  Article  Google Scholar 

  3. 3.

    Dougados M (2001) The role of anti-inflammatory drugs in the treatment of osteoarthritis: a European viewpoint. Clin Exp Rheumatol 19:S9–S14

    PubMed  Article  CAS  Google Scholar 

  4. 4.

    Pincus T, Koch GG, Sokka T et al (2001) A randomized, double-blind, crossover clinical trial of diclofenac plus misoprostol versus acetaminophen in patients with osteoarthritis of the hip or knee. Arthritis Rheum 44:1587–1598

    PubMed  Article  CAS  Google Scholar 

  5. 5.

    Eyigor S, Hepguler S, Sezak M, Oztop F, Capaci K (2006) Effects of intra-articular hyaluronic acid and corticosteroid therapies on articular cartilage in experimental severe osteoarthritis. Clin Exp Rheumatol 24:724

    PubMed  CAS  Google Scholar 

  6. 6.

    Karatosun V, Unver B, Ozden A, Ozay Z, Gunal I (2008) Intra-articular hyaluronic acid compared to exercise therapy in osteoarthritis of the ankle. A prospective randomized trial with long-term follow-up. Clin Exp Rheumatol 26:288–294

    PubMed  CAS  Google Scholar 

  7. 7.

    Schroeppel JP, Crist JD, Anderson HC, Wang J (2011) Molecular regulation of articular chondrocyte function and its significance in osteoarthritis. Histol Histopathol 26:377–394

    PubMed  CAS  Google Scholar 

  8. 8.

    Hunziker EB (2002) Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. Osteoarthritis Cartilage 10:432–463

    PubMed  Article  CAS  Google Scholar 

  9. 9.

    Steinert AF, Ghivizzani SC, Rethwilm A, Tuan RS, Evans CH, Noth U (2007) Major biological obstacles for persistent cell-based regeneration of articular cartilage. Arthritis Res Ther 9:213

    PubMed  Article  Google Scholar 

  10. 10.

    Chen FH, Tuan RS (2008) Mesenchymal stem cells in arthritic diseases. Arthritis Res Ther 10:223

    PubMed  Article  Google Scholar 

  11. 11.

    Prockop DJ (1997) Marrow stromal cells as stem cells for non-hematopoietic tissues. Science 276:71–74

    PubMed  Article  CAS  Google Scholar 

  12. 12.

    Zuk PA, Zhu M, Ashjian P et al (2002) Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 13:4279–4295

    PubMed  Article  CAS  Google Scholar 

  13. 13.

    Romanov YA, Svintsitskaya VA, Smirnov VN (2003) Searching for alternative sources of postnatal human mesenchymal stem cells: candidate MSC-like cells from umbilical cord. Stem Cells 21:105–110

    PubMed  Article  Google Scholar 

  14. 14.

    Fukuchi Y, Nakajima H, Sugiyama D, Hirose I, Kitamura T, Tsuji K (2004) Human placenta-derived cells have mesenchymal stem/progenitor cell potential. Stem Cells 22:649–658

    PubMed  Article  CAS  Google Scholar 

  15. 15.

    De Bari C, Dell’Accio F, Tylzanowski P, Luyten FP (2001) Multipotent mesenchymal stem cells from adult human synovial membrane. Arthritis Rheum 44:1928–1942

    PubMed  Article  Google Scholar 

  16. 16.

    Zarnett R, Salter RB (1989) Periosteal neochondrogenesis for biologically resurfacing joints: its cellular origin. Can J Surg 32:171–174

    PubMed  CAS  Google Scholar 

  17. 17.

    Peng H, Huard J (2004) Muscle-derived stem cells for musculoskeletal tissue regeneration and repair. Transpl Immunol 12:311–319

    PubMed  Article  CAS  Google Scholar 

  18. 18.

    Fraser JK, Wulur I, Alfonso Z, Hedrick MH (2006) Fat tissue: an underappreciated source of stem cells for biotechnology. Trends Biotechnol 24:150–154

    PubMed  Article  CAS  Google Scholar 

  19. 19.

    Sakaguchi Y, Sekiya I, Yagishita K, Muneta T (2005) Comparison of human stem cells derived from various mesenchymal tissues: superiority of synovium as a cell source. Arthritis Rheum 52:2521–2529

    PubMed  Article  Google Scholar 

  20. 20.

    Kern S, Eichler H, Stoeve J, Kluter H, Bieback K (2006) Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells 24:1294–1301

    PubMed  Article  CAS  Google Scholar 

  21. 21.

    Sotiropoulou PA, Perez SA, Salagianni M, Baxevanis CN, Papamichail M (2006) Characterization of the optimal culture conditions for clinical scale production of human mesenchymal stem cells. Stem Cells 24:462–471

    PubMed  Article  Google Scholar 

  22. 22.

    Murphy JM, Dixon K, Beck S, Fabian D, Feldman A, Barry F (2002) Reduced chondrogenic and adipogenic activity of mesenchymal stem cells from patients with advanced osteoarthritis. Arthritis Rheum 46:704–713

    PubMed  Article  Google Scholar 

  23. 23.

    Kafienah W, Mistry S, Dickinson SC, Sims TJ, Learmonth I, Hollander AP (2007) Three-dimensional cartilage tissue engineering using adult stem cells from osteoarthritis patients. Arthritis Rheum 56:177–187

    PubMed  Article  Google Scholar 

  24. 24.

    Scharstuhl A, Schewe B, Benz K, Gaissmaier C, Buhring HJ, Stoop R (2007) Chondrogenic potential of human adult mesenchymal stem cells is independent of age or osteoarthritis etiology. Stem Cell 25:3244–3251

    Article  CAS  Google Scholar 

  25. 25.

    Dudics V, Kunstar A, Kovacs J et al (2009) Chondrogenic potential of mesenchymal stem cells from patients with rheumatoid arthritis and osteoarthritis: measurements in a microculture system. Cells Tissues Organs 189:307–316

    PubMed  Article  CAS  Google Scholar 

  26. 26.

    Jorgensen C, Djouad F, Fritz V, Apparailly F, Plence P, Noel D (2003) Mesenchymal stem cells and rheumatoid arthritis. Joint Bone Spine 70:483–485

    PubMed  Article  Google Scholar 

  27. 27.

    Uccelli A, Pistoia V, Moretta L (2007) Mesenchymal stem cells: a new strategy for immunosuppression? Trends Immunol 28:219–226

    PubMed  Article  CAS  Google Scholar 

  28. 28.

    Chen X, Armstrong MA, Li G (2006) Mesenchymal stem cells in immunoregulation. Immunol Cell Biol 84:413–421

    PubMed  Article  CAS  Google Scholar 

  29. 29.

    Caplan AI, Dennis JE (2006) Mesenchymal stem cells as trophic mediators. J Cell Biochem 98:1076–1084

    PubMed  Article  CAS  Google Scholar 

  30. 30.

    Koelling S, Miosge N (2009) Stem cell therapy for cartilage regeneration in osteoarthritis. Expert Opin Biol Ther 9:1399–1405

    PubMed  Article  Google Scholar 

  31. 31.

    Fan H, Hu Y, Zhang C, Li X, Lv R, Qin L, Zhu R (2006) Cartilage regeneration using mesenchymal stem cells and a PLGA-gelatin/chondroitin/hyaluronate hybrid scaffold. Biomaterials 27:4573–4580

    PubMed  Article  CAS  Google Scholar 

  32. 32.

    Qi Y, Zhao T, Xu K, Dai T, Yan W (2011) The restoration of full-thickness cartilage defects with mesenchymal stem cells (MSCs) loaded and cross-linked bilayer collagen scaffolds on rabbit model. Mol Biol Rep. doi: 10.1007/s11033-011-0853-8

  33. 33.

    Qi YY, Chen X, Jiang YZ et al (2009) Local delivery of autologous platelet in collagen matrix simulated in situ articular cartilage repair. Cell Transplant 18:1161–1169

    PubMed  Article  Google Scholar 

  34. 34.

    Wang W, Li B, Yang J et al (2010) The restoration of full-thickness cartilage defects with BMSCs and TGF-beta 1 loaded PLGA/fibrin gel constructs. Biomaterials 31:8964–8973

    PubMed  Article  CAS  Google Scholar 

  35. 35.

    Lee KB, Hui JH, Song IC, Ardany L, Lee EH (2007) Injectable mesenchymal stem cell therapy for large cartilage defects–a porcine model. Stem Cells 25:2964–2971

    PubMed  Article  Google Scholar 

  36. 36.

    Horie M, Sekiya I, Muneta T et al (2009) Intra-articular Injected synovial stem cells differentiate into meniscal cells directly and promote meniscal regeneration without mobilization to distant organs in rat massive meniscal defect. Stem Cells 27:878–887

    PubMed  Article  CAS  Google Scholar 

  37. 37.

    Agung M, Ochi M, Yanada S, Adachi N, Izuta Y, Yamasaki T, Toda K (2006) Mobilization of bone marrow-derived mesenchymal stem cells into the injured tissues after intraarticular injection and their contribution to tissue regeneration. Knee Surg Sports Traumatol Arthrosc 14:1307–1314

    PubMed  Article  Google Scholar 

  38. 38.

    Chen WP, Bao JP, Hu PF, Feng J, Wu LD (2010) Alleviation of osteoarthritis by Trichostatin A, a histone deacetylase inhibitor, in experimental osteoarthritis. Mol Biol Rep 37:3967–3972

    PubMed  Article  CAS  Google Scholar 

  39. 39.

    Murphy JM, Fink DJ, Hunziker EB, Barry FP (2003) Stem cell therapy in a caprine model of osteoarthritis. Arthritis Rheum 48:3464–3474

    PubMed  Article  Google Scholar 

  40. 40.

    van der Kraan PM, Vitters EL, van de Putte LB, van den Berg WB (1989) Development of osteoarthritic lesions in mice by “metabolic” and “mechanical” alterations in the knee joints. Am J Pathol 135:1001–1014

    PubMed  Google Scholar 

  41. 41.

    Guingamp C, Gegout-Pottie P, Philippe L, Terlain B, Netter P, Gillet P (1997) Mono-iodoacetate-induced experimental osteoarthritis: a dose-response study of loss of mobility, morphology, and biochemistry. Arthritis Rheum 40:1670–1679

    PubMed  Article  CAS  Google Scholar 

  42. 42.

    Janusz MJ, Hookfin EB, Heitmeyer SA et al (2001) Moderation of iodoacetate-induced experimental osteoarthritis in rats by matrix metalloproteinase inhibitors. Osteoarthritis Cartilage 9:751–760

    PubMed  Article  CAS  Google Scholar 

  43. 43.

    Stoop R, Buma P, van der Kraan PM et al (2001) Type II collagen degradation in articular cartilage fibrillation after anterior cruciate ligament transection in rats. Osteoarthritis Cartilage 9:308–315

    PubMed  Article  CAS  Google Scholar 

  44. 44.

    Janusz MJ, Bendele AM, Brown KK, Taiwo YO, Hsieh L, Heitmeyer SA (2002) Induction of osteoarthritis in the rat by surgical tear of the meniscus: inhibition of joint damage by a matrix metalloproteinase inhibitor. Osteoarthritis Cartilage 10:785–791

    PubMed  Article  CAS  Google Scholar 

  45. 45.

    Jean YH, Wen ZH, Chang YC et al (2006) Hyaluronic acid attenuates osteoarthritis development in the anterior cruciate ligament-transected knee: association with excitatory amino acid release in the joint dialysate. J Orthop Res 24:1052–1061

    PubMed  Article  CAS  Google Scholar 

  46. 46.

    Frisbie DD, Kisiday JD, Kawcak CE, Werpy NM, McIlwraith CW (2009) Evaluation of adipose-derived stromal vascular fraction or bone marrow-derived mesenchymal stem cells for treatment of osteoarthritis. J Orthop Res 27:1675–1680

    PubMed  Article  Google Scholar 

  47. 47.

    Toghraie FS, Chenari N, Gholipour MA, Faghih Z, Torabinejad S, Dehghani S, Ghaderi A (2011) Treatment of osteoarthritis with infrapatellar fat pad derived mesenchymal stem cells in Rabbit. Knee 18:71–75

    PubMed  Article  CAS  Google Scholar 

  48. 48.

    Augello A, Tasso R, Negrini SM, Cancedda R, Pennesi G (2007) Cell therapy using allogeneic bone marrow mesenchymal stem cells prevents tissue damage in collagen-induced arthritis. Arthritis Rheum 56:1175–1186

    PubMed  Article  CAS  Google Scholar 

  49. 49.

    Black LL, Gaynor J, Gahring D et al (2007) Effect of adipose-derived mesenchymal stem and regenerative cells on lameness in dogs with chronic osteoarthritis of the coxofemoral joints: a randomized, double-blinded, multicenter, controlled trial. Vet Ther 8:272–284

    PubMed  Google Scholar 

  50. 50.

    Black LL, Gaynor J, Adams C et al (2008) Effect of intraarticular injection of autologous adipose-derived mesenchymal stem and regenerative cells on clinical signs of chronic osteoarthritis of the elbow joint in dogs. Vet Ther 9:192–200

    PubMed  Google Scholar 

  51. 51.

    Huang K, Zhang C, Zhang XW, Bao JP, Wu LD (2011) Effect of dehydroepiandrosterone on aggrecanase expression in articular cartilage in a rabbit model of osteoarthritis. Mol Biol Rep 38:3569–3572

    PubMed  Article  CAS  Google Scholar 

  52. 52.

    Roberts S, Genever P, McCaskie A, Bari CD (2011) Prospects of stem cell therapy in osteoarthritis. Regen Med 6:351–366

    PubMed  Article  Google Scholar 

  53. 53.

    Wakitani S, Imoto K, Yamamoto T, Saito M, Murata N, Yoneda M (2002) Human autologous culture expanded bone marrow mesenchymal cell transplantation for repair of cartilage defects in osteoarthritic knees. Osteoarthritis Cartilage 10:199–206

    PubMed  Article  CAS  Google Scholar 

  54. 54.

    Centeno CJ, Busse D, Kisiday J, Keohan C, Freeman M, Karli D (2008) Increased knee cartilage volume in degenerative joint disease using percutaneously implanted, autologous mesenchymal stem cells. Pain Physician 11:343–353

    PubMed  Google Scholar 

  55. 55.

    Davatchi F, Abdollahi BS, Mohyeddin M, Shahram F, Nikbin B (2011) Mesenchymal stem cell therapy for knee osteoarthritis. Preliminary report of four patients. Int J Rheum Dis 14:211–215

    PubMed  Article  Google Scholar 

  56. 56.

    Noth U, Steinert AF, Tuan RS (2008) Technology insight: adult mesenchymal stem cells for osteoarthritis therapy. Nat Clin Pract Rheumatol 4:371–380

    PubMed  Google Scholar 

  57. 57.

    Evans CH, Ghivizzani SC, Robbins PD (2006) Will arthritis gene therapy become a clinical reality? Nat Clin Pract Rheumatol 2:344–345

    PubMed  Article  Google Scholar 

  58. 58.

    Evans CH, Gouze JN, Gouze E, Robbins PD, Ghivizzani SC (2004) Osteoarthritis gene therapy. Gene Ther 11:379–389

    PubMed  Article  CAS  Google Scholar 

  59. 59.

    Hu B, Ren JL, Zhang JR, Ma Q, Liu YP, Mao TQ (2010) Enhanced treatment of articular cartilage defect of the knee by intra-articular injection of Bcl-xL-engineered mesenchymal stem cells in rabbit model. J Tissue Eng Regen Med 4:105–114

    PubMed  Article  CAS  Google Scholar 

  60. 60.

    Matsumoto T, Cooper GM, Gharaibeh B (2009) Cartilage repair in a rat model of osteoarthritis through intraarticular transplantation of muscle-derived stem cells expressing bone morphogenetic protein 4 and soluble Flt-1. Arthritis Rheum 60:1390–1405

    PubMed  Article  Google Scholar 

  61. 61.

    Evans CH, Robbins PD, Ghivizzani SC (1996) Clinical trial to assess the safety, feasibility, and efficacy of transferring a potentially anti-arthritic cytokine gene to human joints with rheumatoid arthritis. Hum Gene Ther 7:1261–1280

    PubMed  Article  CAS  Google Scholar 

  62. 62.

    Evans CH, Robbins PD, Ghivizzani SC (2005) Gene transfer to human joints: progress toward a gene therapy of arthritis. Proc Natl Acad Sci USA 102:8698–8703

    PubMed  Article  CAS  Google Scholar 

  63. 63.

    Centeno CJ, Schultz JR, Cheever M, Robinson B, Freeman M, Marasco W (2010) Safety and complications reporting on the re-implantation of culture-expanded mesenchymal stem cells using autologous platelet lysate technique. Curr Stem Cell Res Ther 5:81–93

    PubMed  Article  CAS  Google Scholar 

  64. 64.

    Alfaqeh H, Norhamdan MY, Chua KH, Chen HC, Aminuddin BS, Ruszymah BH (2008) Cell based therapy for osteoarthritis in a sheep model: gross and histological assessment. Med J Malaysia 63:S37–S38

    Google Scholar 

  65. 65.

    Koelling S, Kruegel J, Irmer M, Path JR, Sadowski B, Miro X, Miosge N (2009) Migratory chondrogenic progenitor cells from repair tissue during the later stages of human osteoarthritis. Cell Stem Cell 4:324–335

    PubMed  Article  CAS  Google Scholar 

Download references


The project was supported by the Science Technology Program of Zhejiang Province (2008C13025) and the Natural Science Foundation of China (81071259)

Conflicts of interest

All authors have no conflicts of interest.

Author information



Corresponding author

Correspondence to Weiqi Yan.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Qi, Y., Feng, G. & Yan, W. Mesenchymal stem cell-based treatment for cartilage defects in osteoarthritis. Mol Biol Rep 39, 5683–5689 (2012).

Download citation


  • Osteoarthritis
  • Mesenchymal stem cells
  • Cartilage defects
  • Intra-articular injection