Skip to main content
SpringerLink
Log in

Mesenchymal stem cells for the treatment of cartilage lesions: from preclinical findings to clinical application in orthopaedics

  • Sports Medicine
  • Published:
Knee Surgery, Sports Traumatology, Arthroscopy Aims and scope

Abstract

Purpose

The aim of this systematic review is to examine the available clinical evidence in the literature to support mesenchymal stem cell (MSC) treatment strategies in orthopaedics for cartilage defect regeneration.

Methods

The research was performed on the PubMed database considering the English literature from 2002 and using the following key words: cartilage, cartilage repair, mesenchymal stem cells, MSCs, bone marrow concentrate (BMC), bone marrow-derived mesenchymal stem cells, bone marrow stromal cells, adipose-derived mesenchymal stem cells, and synovial-derived mesenchymal stem cells.

Results

The systematic research showed an increasing number of published studies on this topic over time and identified 72 preclinical papers and 18 clinical trials. Among the 18 clinical trials identified focusing on cartilage regeneration, none were randomized, five were comparative, six were case series, and seven were case reports; two concerned the use of adipose-derived MSCs, five the use of BMC, and 11 the use of bone marrow-derived MSCs, with preliminary interesting findings ranging from focal chondral defects to articular osteoarthritis degeneration.

Conclusions

Despite the growing interest in this biological approach for cartilage regeneration, knowledge on this topic is still preliminary, as shown by the prevalence of preclinical studies and the presence of low-quality clinical studies. Many aspects have to be optimized, and randomized controlled trials are needed to support the potential of this biological treatment for cartilage repair and to evaluate advantages and disadvantages with respect to the available treatments.

Level of evidence

IV.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Adachi N, Ochi M, Deie M, Ito Y (2005) Transplant of mesenchymal stem cells and hydroxyapatite ceramics to treat severe osteochondral damage after septic arthritis of the knee. J Rheumatol 32(8):1615–1618

    PubMed  Google Scholar 

  2. Breitbach M, Bostani T, Roell W, Xia Y, Dewald O, Nygren JM, Fries JW, Tiemann K, Bohlen H, Hescheler J, Welz A, Bloch W, Jacobsen SE, Fleischmann BK (2007) Potential risks of bone marrow cell transplantation into infarcted hearts. Blood 110(4):1362–1369

    Article  PubMed  CAS  Google Scholar 

  3. Buda R, Vannini F, Cavallo M, Grigolo B, Cenacchi A, Giannini S (2010) Osteochondral lesions of the knee: a new one-step repair technique with bone-marrow-derived cells. J Bone Joint Surg Am 92(2):2–11

    Article  PubMed  Google Scholar 

  4. Cao L, Yang F, Liu G, Yu D, Li H, Fan Q, Gan Y, Tang T, Dai K (2011) The promotion of cartilage defect repair using adenovirus mediated Sox9 gene transfer of rabbit bone marrow mesenchymal stem cells. Biomaterials 32(16):3910–3920

    Article  PubMed  CAS  Google Scholar 

  5. Caplan AI, Dennis JE (2006) Mesenchymal stem cells as trophic mediators. J Cell Biochem 98(5):1076–1084

    Article  PubMed  CAS  Google Scholar 

  6. Caplan AI, Koutroupas S (1973) The control of muscle and cartilage development in the chick limb: the role of differential vascularization. J Embryol Exp Morphol 29(3):571–583

    PubMed  CAS  Google Scholar 

  7. Caplan AI (2005) Review: mesenchymal stem cells: cell-based reconstructive therapy in orthopedics. Tissue Eng 11(7–8):1198–1211

    Article  PubMed  CAS  Google Scholar 

  8. 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(3):343–353

    PubMed  Google Scholar 

  9. Chang CH, Kuo TF, Lin FH, Wang JH, Hsu YM, Huang HT, Loo ST, Fang HW, Liu HC, Wang WC (2011) Tissue engineering-based cartilage repair with mesenchymal stem cells in a porcine model. J Orthop Res 29(12):1874–1880

    Article  PubMed  CAS  Google Scholar 

  10. Chen FH (2008) Mesenchymal stem cells in arthritic diseases. Arthr Res Ther 10(5):223

    Article  Google Scholar 

  11. Chen WC, Yao CL, Wei YH, Chu IM (2011) Evaluating osteochondral defect repair potential of autologous rabbit bone marrow cells on type II collagen scaffold. Cytotechnology 63(1):13–23

    Article  PubMed  Google Scholar 

  12. Chen J, Chen H, Li P, Diao H, Zhu S, Dong L, Wang R, Guo T, Zhao J, Zhang J (2011) Simultaneous regeneration of articular cartilage and subchondral bone in vivo using MSCs induced by a spatially controlled gene delivery system in bilayered integrated scaffolds. Biomaterials 32(21):4793–4805

    Article  PubMed  CAS  Google Scholar 

  13. Cucchiarini M, Ekici M, Schetting S, Kohn D, Madry H (2011) Metabolic activities and chondrogenic differentiation of human mesenchymal stem cells following recombinant adeno-associated virus-mediated gene transfer and overexpression of fibroblast growth factor 2. Tissue Eng Part A 17(15–16):1921–1933

    Article  PubMed  CAS  Google Scholar 

  14. Cucchiarini M, Madry H (2005) Gene therapy for cartilage defects. J Gene Med 7(12):1495–1509

    Article  PubMed  CAS  Google Scholar 

  15. 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(2):211–215

    Article  PubMed  Google Scholar 

  16. De Bari C, Dell’Accio F, Karystinou A, Guillot PV, Fisk NM, Jones EA, McGonagle D, Khan IM, Archer CW, Mitsiadis TA, Donaldson AN, Luyten FP, Pitzalis C (2008) A biomarker-based mathematical model to predict bone-forming potency of human synovial and periosteal mesenchymal stem cells. Arthritis Rheum 58(1):240–250

    Article  PubMed  Google Scholar 

  17. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop Dj, Horwitz E (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8(4):315–317

    Article  PubMed  CAS  Google Scholar 

  18. Dragoo JL, Carlson G, McCormick F, Khan-Farooqi H, Zhu M, Zuk PA, Benhaim P (2007) Healing full-thickness cartilage defects using adipose-derived stem cells. Tissue Eng 13(7):1615–1621

    Article  PubMed  CAS  Google Scholar 

  19. Emadedin M, Aghdami N, Taghiyar L, Fazeli R, Moghadasali R, Jahangir S, Farjad R, Baghaban Eslaminejad M (2012) Intra-articular injection of autologous mesenchymal stem cells in six patients with knee osteoarthritis. Arch Iran Med 15(7):422–428

    PubMed  Google Scholar 

  20. Fortier LA, Potter HG, Rickey EJ, Schnabel LV, Foo LF, Chong LR, Stokol T, Cheetham J, Nixon AJ (2010) Concentrated bone marrow aspirate improves full-thickness cartilage repair compared with microfracture in the equine model. J Bone Joint Surg Am 92(10):1927–1937

    Article  PubMed  Google Scholar 

  21. Friedenstein AJ, Piatetzky-Shapiro II, Petrakova KV (1966) Osteogenesis in transplants of bone marrow cells. J Embryol Exp Morphol 6(3):381–390

    Google Scholar 

  22. Frisbie DD, Lu Y, Kawcak CE, DiCarlo EF, Binette F, McIlwraith CW (2009) In vivo evaluation of autologous cartilage fragment-loaded scaffolds implanted into equine articular defects and compared with autologous chondrocyte implantation. Am J Sports Med 37(1):71S–80S

    Article  PubMed  Google Scholar 

  23. Giannini S, Buda R, Cavallo M, Ruffilli A, Cenacchi A, Cavallo C, Vannini F (2010) Cartilage repair evolution in post-traumatic osteochondral lesions of the talus: from open field autologous chondrocyte to bone-marrow-derived cells transplantation. Injury 41(11):1196–1203

    Article  PubMed  Google Scholar 

  24. Giannini S, Buda R, Vannini F, Cavallo M, Grigolo B (2009) One-step bone marrow-derived cell transplantation in talar osteochondral lesions. Clin Orthop Relat Res 467(12):3307–3320

    Article  PubMed  Google Scholar 

  25. Gigante A, Calcagno S, Cecconi S, Ramazzotti D, Manzotti S, Enea D (2011) Use of collagen scaffold and autologous bone marrow concentrate as a one-step cartilage repair in the knee: histological results of second-look biopsies at 1 year follow-up. Int J Immunopathol Pharmacol 24(1 Suppl 2):69–72

    PubMed  CAS  Google Scholar 

  26. Gobbi A, Karnatzikos G, Scotti C, Mahajan V, Mazzucco L, Grigolo B (2011) One-step cartilage repair with bone marrow aspirate concentrated cells and collagen matrix in full-thickness knee cartilage lesions: results at 2 year follow up. Cartilage 2(3):286–299

    Article  Google Scholar 

  27. Grande DA, Mason J, Light E, Dines D (2003) Stem cells as platforms for delivery of genes to enhance cartilage repair. J Bone Joint Surg Am 85-A(2):111–116

    PubMed  Google Scholar 

  28. Guo X, Zheng Q, Yang S, Shao Z, Yuan Q, Pan Z, Tang S, Liu K, Quan D (2006) Repair of full-thickness articular cartilage defects by cultured mesenchymal stem cells transfected with the transforming growth factor beta1 gene. Biomed Mater 1(4):206–215

    Article  PubMed  CAS  Google Scholar 

  29. Haleem AM, Singergy AA, Sabry D, Atta HM, Rashed LA, Chu CR, El Shewy MT, Azzam A, Abdel Aziz MT (2010) The clinical use of human culture-expanded autologous bone marrow mesenchymal stem cells transplanted on platelet-rich fibrin glue in the treatment of articular cartilage defects: a pilot study and preliminary results. Cartilage 1(4):253–261

    Article  PubMed  Google Scholar 

  30. He Q, Wan C, Li G (2007) Concise review: multipotent mesenchymal stromal cells in blood. Stem Cells 25(1):69–77

    Article  PubMed  CAS  Google Scholar 

  31. Hori J, Deie M, Kobayashi T, Yasunaga Y, Kawamata S, Ochi M (2011) Articular cartilage repair using an intra-articular magnet and synovium-derived cells. J Orthop Res 29(4):531–538

    Article  PubMed  Google Scholar 

  32. Horwitz EM, Le Blanc K, Dominici M, Mueller I, Slaper-Cortenbach I, Marini FC, Deans RJ, Krause DS, Keating A (2005) International Society for Cellular Therapy. Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement. Cytotherapy 7(5):393–395

    Article  PubMed  CAS  Google Scholar 

  33. Im GI, Lee JH (2010) Repair of osteochondral defects with adipose stem cells and a dual growth factor-releasing scaffold in rabbits. J Biomed Mater Res B Appl Biomater 92(2):552–560

    PubMed  Google Scholar 

  34. Im GI, Kim HJ, Lee JH (2011) Chondrogenesis of adipose stem cells in a porous PLGA scaffold impregnated with plasmid DNA containing SOX trio (SOX-5, -6 and -9) genes. Biomaterials 32(19):4385–4392

    Article  PubMed  CAS  Google Scholar 

  35. Ivkovic A, Pascher A, Hudetz D, Maticic D, Jelic M, Dickinson S, Loparic M, Haspl M, Windhager R, Pecina M (2010) Articular cartilage repair by genetically modified bone marrow aspirate in sheep. Gene Ther 17(6):779–789

    Article  PubMed  CAS  Google Scholar 

  36. Kasemkijwattana C, Hongeng S, Kesprayura S, Rungsinaporn V, Chaipinyo K, Chansiri K (2011) Autologous bone marrow mesenchymal stem cells implantation for cartilage defects: two cases report. J Med Assoc Thai 94(3):395–400

    PubMed  Google Scholar 

  37. Katayama R, Wakitani S, Tsumaki N, Morita Y, Matsushita I, Gejo R, Kimura T (2004) Repair of articular cartilage defects in rabbits using CDMP1 gene-transfected autologous mesenchymal cells derived from bone marrow. Rheumatology (Oxford) 43(8):980–985

    Article  CAS  Google Scholar 

  38. Kim HJ, Im GI (2009) Chondrogenic differentiation of adipose tissue-derived mesenchymal stem cells: greater doses of growth factor are necessary. J Orthop Res 27(5):612–619

    Article  PubMed  Google Scholar 

  39. Koga H, Muneta T, Ju YJ, Nagase T, Nimura A, Mochizuki T, Ichinose S, von der Mark K, Sekiya I (2007) Synovial stem cells are regionally specified according to local microenvironments after implantation for cartilage regeneration. Stem Cells 25(3):689–696

    Article  PubMed  CAS  Google Scholar 

  40. Koga H, Engebretsen L, Brinchmann JE, Muneta T, Sekiya I (2009) Mesenchymal stem cell-based therapy for cartilage repair: a review. Knee Surg Sports Traumatol Arthrosc 17:1289–1297

    Article  PubMed  Google Scholar 

  41. Koga H, Muneta T, Nagase T, Nimura A, Ju YJ, Mochizuki T, Sekiya I (2008) Comparison of mesenchymal tissues-derived stem cells for in vivo chondrogenesis: suitable conditions for cell therapy of cartilage defects in rabbit. Cell Tissue Res 333(2):207–215

    Article  PubMed  Google Scholar 

  42. Koh YG, Choi YJ (2012) Infrapatellar fat pad-derived mesenchymal stem cell therapy for knee osteoarthritis. Knee doi:10.1016/j.knee.2012.04.001 (epub 14 May 2012)

  43. Kon E, Filardo G, Roffi A, Andriolo L, Marcacci M (2012) New trends for knee cartilage regeneration: from cell-free scaffolds to mesenchymal stem cells. Curr Rev Musculoskelet Med 5(3):236–243

    Article  PubMed  Google Scholar 

  44. Krampera M, Pizzolo G, Aprili G, Franchini M (2006) Mesenchymal stem cells for bone, cartilage, tendon and skeletal muscle repair. Bone 39:678–683

    Article  PubMed  CAS  Google Scholar 

  45. Kubo S, Cooper GM, Matsumoto T, Phillippi JA, Corsi KA, Usas A, Li G, Fu FH, Huard J (2009) Blocking vascular endothelial growth factor with soluble Flt-1 improves the chondrogenic potential of mouse skeletal muscle-derived stem cells. Arthritis Rheum 60(1):155–165

    Article  PubMed  CAS  Google Scholar 

  46. Kuroda R, Ishida K, Matsumoto T, Akisue T, Fujioka H, Mizuno K, Ohgushi H, Wakitani S, Kurosaka M (2007) Treatment of a full-thickness articular cartilage defect in the femoral condyle of an athlete with autologous bone-marrow stromal cells. Osteoarthritis Cartilage 15(2):226–231

    Article  PubMed  CAS  Google Scholar 

  47. Kuroda R, Usas A, Kubo S, Corsi K, Peng H, Rose T, Cummins J, Fu FH, Huard J (2006) Cartilage repair using bone morphogenetic protein 4 and muscle-derived stem cells. Arthritis Rheum 54(2):433–442

    Article  PubMed  CAS  Google Scholar 

  48. Lee JM, Kim BS, Lee H, Im GI (2012) In vivo tracking of mesenchymal stem cells using fluorescent nanoparticles in an osteochondral repair model. Mol Ther 20(7):1434–1442

    Article  PubMed  CAS  Google Scholar 

  49. Lee JM, Im GI (2012) SOX trio-co-transduced adipose stem cells in fibrin gel to enhance cartilage repair and delay the progression of osteoarthritis in the rat. Biomaterials 33(7):2016–2024

    Article  PubMed  CAS  Google Scholar 

  50. Liechty KW, MacKenzie TC, Shaaban AF, Radu A, Moseley AM, Deans R, Marshak DR, Flake AW (2000) Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep. Nat Med 6(11):1282–1286

    Article  PubMed  CAS  Google Scholar 

  51. Liu TM, Guo XM, Tan HS, Hui JH, Lim B, Lee EH (2011) Zinc-finger protein 145, acting as an upstream regulator of SOX9, improves the differentiation potential of human mesenchymal stem cells for cartilage regeneration and repair. Arthritis Rheum 63(9):2711–2720

    Article  PubMed  CAS  Google Scholar 

  52. Lodi D, Iannitti T, Palmieri B (2011) Stem cells in clinical practice: applications and warnings. J Exp Clin Cancer Res 30:9

    Article  PubMed  Google Scholar 

  53. Madry H, Grün UW, Knutsen G (2011) Cartilage repair and joint preservation: medical and surgical treatment options. Dtsch Arztebl Int 108(40):669–677

    PubMed  Google Scholar 

  54. Masuoka K, Asazuma T, Hattori H, Yoshihara Y, Sato M, Matsumura K, Matsui T, Takase B, Nemoto K, Ishihara M (2006) Tissue engineering of articular cartilage with autologous cultured adipose tissue-derived stromal cells using atelocollagen honeycomb-shaped scaffold with a membrane sealing in rabbits. J Biomed Mater Res B Appl Biomater 79(1):25–34

    PubMed  Google Scholar 

  55. McIlwraith CW, Frisbie DD, Rodkey WG, Kisiday JD, Werpy NM, Kawcak CE, Steadman JR (2011) Evaluation of intra-articular mesenchymal stem cells to augment healing of microfractured chondral defects. Arthroscopy 27(11):1552–1561

    Article  PubMed  Google Scholar 

  56. Mimura T, Imai S, Okumura N, Li L, Nishizawa K, Araki S, Ueba H, Kubo M, Mori K, Matsusue Y (2011) Spatiotemporal control of proliferation and differentiation of bone marrow-derived mesenchymal stem cells recruited using collagen hydrogel for repair of articular cartilage defects. J Biomed Mater Res B Appl Biomater 98B(2):360–368

    Article  CAS  Google Scholar 

  57. Mokbel AN, El Tookhy OS, Shamaa AA, Rashed LA, Sabry D, El Sayed AM (2011) Homing and reparative effect of intra-articular injection of autologus mesenchymal stem cells in osteoarthritic animal model. BMC Musculoskelet Disord 15(12):259

    Article  Google Scholar 

  58. Mosna F, Sensebé L, Krampera M (2010) Human bone marrow and adipose tissue mesenchymal stem cells: a user’s guide. Stem Cells Dev 19(10):1449–1470

    Article  PubMed  CAS  Google Scholar 

  59. Mueller MB, Tuan RS (2008) Functional characterization of hypertrophy in chondrogenesis of human mesenchymal stem cells. Arthritis Rheum 58(5):1377–1388

    Article  PubMed  CAS  Google Scholar 

  60. Nathan S, De Das S, Thambyah A, Fen C, Goh J, Lee EH (2003) Cell-based therapy in the repair of osteochondral defects: a novel use for adipose tissue. Tissue Eng 9(4):733–744

    Article  PubMed  CAS  Google Scholar 

  61. Nejadnik H, Hui JH, Feng Choong EP, Tai BC, Lee EH (2010) Autologous bone marrow-derived mesenchymal stem cells versus autologous chondrocyte implantation: an observational cohort study. Am J Sports Med 38(6):1110–1116

    Article  PubMed  Google Scholar 

  62. Pagnotto MR, Wang Z, Karpie JC, Ferretti M, Xiao X, Chu CR (2007) Adeno-associated viral gene transfer of transforming growth factor-beta1 to human mesenchymal stem cells improves cartilage repair. Gene Ther 14(10):804–813

    Article  PubMed  CAS  Google Scholar 

  63. Pak J (2011) Regeneration of human bones in hip osteonecrosis and human cartilage in knee osteoarthritis with autologous adipose-tissue-derived stem cells: a case series. J Med Case Rep 5:296

    Article  PubMed  Google Scholar 

  64. Park J, Gelse K, Frank S, von der Mark K, Aigner T, Schneider H (2006) Transgene-activated mesenchymal stem cells for articular cartilage repair: a comparison of primary bone marrow-, perichondrium/periosteum- and fat-derived cells. J Gene Med 8(1):112–125

    Article  PubMed  CAS  Google Scholar 

  65. Quarto R, Mastrogiacomo M, Cancedda R, Kutepov SM, Mukhachev V, Lavroukov A, Kon E, Marcacci M (2001) Repair of large bone defects with the use of autologous bone marrow stromal cells. N Engl J Med 344(5):385–386

    Article  PubMed  CAS  Google Scholar 

  66. Re’em T, Witte F, Willbold E, Ruvinov E, Cohen S (2012) Simultaneous regeneration of articular cartilage and subchondral bone induced by spatially presented TGF-beta and BMP-4 in a bilayer affinity binding system. Acta Biomater 8(9):3283–3293

    Article  PubMed  Google Scholar 

  67. Rubio D, Garcia-Castro J, Martín MC, de la Fuente R, Cigudosa JC, Lloyd AC, Bernad A (2005) Spontaneous human adult stem cell transformation. Cancer Res 65(8):3035–3039

    PubMed  CAS  Google Scholar 

  68. 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(8):2521–2529

    Article  PubMed  Google Scholar 

  69. Saw KY, Anz A, Merican S, Tay YG, Ragavanaidu K, Jee CSY, McGuire DA (2011) Articular cartilage regeneration with autologous peripheral blood progenitor cells and hyaluronic acid after arthroscopic subchondral drilling: a report of 5 cases with histology. Arthroscopy 27(4):493–506

    Article  PubMed  Google Scholar 

  70. Saw KY, Hussin P, Loke SC, Azam M, Chen HC, Tay YG, Low S, Wallin KL, Ragavanaidu K (2009) Articular cartilage regeneration with autologous marrow aspirate and hyaluronic acid: an experimental study in a goat model. Arthroscopy 25(12):1391–1400

    Article  PubMed  Google Scholar 

  71. Schäffler A, Büchler C (2007) Concise review: adipose tissue-derived stromal cells-basic and clinical implications for novel cell-based therapies. Stem Cells 25(4):818–827

    Article  PubMed  Google Scholar 

  72. Sensebé L, Krampera M, Schrezenmeier H, Bourin P, Giordano R (2010) Mesenchymal stem cells for clinical application. Vox Sang 98(2):93–107

    Article  PubMed  Google Scholar 

  73. Shimomura K, Ando W, Tateishi K, Nansai R, Fujie H, Hart DA, Kohda H, Kita K, Kanamoto T, Mae T, Nakata K, Shino K, Yoshikawa H, Nakamura N (2010) The influence of skeletal maturity on allogenic synovial mesenchymal stem cell-based repair of cartilage in a large animal model. Biomaterials 31(31):8004–8011

    Article  PubMed  CAS  Google Scholar 

  74. Singer NG, Caplan AI (2011) Mesenchymal stem cells: mechanisms of inflammation. Annu Rev Pathol 6:457–478

    Article  PubMed  CAS  Google Scholar 

  75. Spencer ND, Gimble JM, Lopez MJ (2011) Mesenchymal stromal cells: past, present, and future. Vet Surg 40(2):129–139

    Article  PubMed  Google Scholar 

  76. Sukarto A, Yu C, Flynn LE, Amsden BG (2012) Co-delivery of adipose-derived stem cells and growth factor-loaded microspheres in RGD-grafted N-methacrylate glycol chitosan gels for focal chondral repair. Biomacromolecules 13(8):2490–2502

    Article  PubMed  CAS  Google Scholar 

  77. Varma HS, Dadarya B, Vidyarthi A (2010) The new avenues in the management of osteoarthritis of knee-stem cells. J Indian Med Assoc 108:583–585

    PubMed  CAS  Google Scholar 

  78. Venkatesan JK, Ekici M, Madry H, Schmitt G, Kohn D, Cucchiarini M (2012) SOX9 gene transfer via safe, stable, replication-defective recombinant adeno-associated virus vectors as a novel, powerful tool to enhance the chondrogenic potential of human mesenchymal stem cells. Stem Cell Res Ther 3(3):22

    Article  PubMed  Google Scholar 

  79. Vinatier C, Bouffi C, Merceron C, Gordeladze J, Brondello JM, Jorgensen C, Weiss P, Guicheux J, Noël D (2009) Cartilage tissue engineering: towards a biomaterial-assisted mesenchymal stem cell therapy. Curr Stem Cell Res Ther 4(4):318–329

    Article  PubMed  CAS  Google Scholar 

  80. Wakitani S, Goto T, Pineda SJ, Young RG, Mansour JM, Caplan AI, Goldberg VM (1994) Mesenchymal cell-based repair of large, full-thickness defects of articular cartilage. J Bone Joint Surg Am 76(4):579–592

    PubMed  CAS  Google Scholar 

  81. 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(3):199–206

    Article  PubMed  CAS  Google Scholar 

  82. Wakitani S, Yamamoto T (2002) Response of the donor and recipient cells in mesenchymal cell transplantation to cartilage defect. Microsc Res Tech 58(1):14–18

    Article  PubMed  Google Scholar 

  83. Wakitani S, Mitsuoka T, Nakamura N, Toritsuka Y, Nakamura Y, Horibe S (2004) Autologous bone marrow stromal cell transplantation for repair of full-thickness articular cartilage defects in human patellae: two case reports. Cell Transplant 13(5):595–600

    Article  PubMed  Google Scholar 

  84. Wakitani S, Nawata M, Tensho K, Okabe T, Machida H, Ohgushi H (2007) Repair of articular cartilage defects in the patello-femoral joint with autologous bone marrow mesenchymal cell transplantation: three case reports involving nine defects in five knees. J Tissue Eng Regen Med 1(1):74–79

    Article  PubMed  Google Scholar 

  85. Wakitani S, Okabe T, Horibe S, Mitsuoka T, Saito M, Koyama T, Nawata M, Tensho K, Kato H, Uematsu K, Kuroda R, Kurosaka M, Yoshiya S, Hattori K, Ohgushi H (2011) Safety of autologous bone marrow-derived mesenchymal 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(2):146–150

    Article  PubMed  Google Scholar 

  86. Xie X, Wang Y, Zhao C, Guo S, Liu S, Jia W, Tuan RS, Zhang C (2012) Comparative evaluation of MSCs from bone marrow and adipose tissue seeded in PRP-derived scaffold for cartilage regeneration. Biomaterials 33(29):7008–7018

    Article  PubMed  CAS  Google Scholar 

  87. Zhang Y, Wang F, Chen J, Ning Z, Yang L (2012) Bone marrow-derived mesenchymal stem cells versus bone marrow nucleated cells in the treatment of chondral defects. Int Orthop 36(5):1079–1086

    Article  PubMed  Google Scholar 

  88. Zscharnack M, Hepp P, Richter R, Aigner T, Schulz R, Somerson J, Josten C, Bader A, Marquass B (2010) Repair of chronic osteochondral defects using predifferentiated mesenchymal stem cells in an ovine model. Am J Sports Med 38(9):1857–1869

    Article  PubMed  Google Scholar 

Download references

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Biomechanics Laboratory, III Clinic, Rizzoli Orthopaedic Institute, Via Di Barbiano, 1/10, 40136, Bologna, Italy

    Giuseppe Filardo & Elizaveta Kon

  2. NABI Laboratory, III Clinic, Rizzoli Orthopaedic Institute, Bologna, Italy

    Giuseppe Filardo, Alice Roffi & Elizaveta Kon

  3. Experimental Orthopaedics and Osteoarthritis Research, Saarland University, Homburg, Germany

    Henning Madry & Magali Cucchiarini

  4. Department of Orthopaedic Surgery, Clinical Hospital Center, University of Zagreb, Zagreb, Croatia

    Mislav Jelic

Authors
  1. Giuseppe Filardo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Henning Madry
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mislav Jelic
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alice Roffi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Magali Cucchiarini
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Elizaveta Kon
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Elizaveta Kon.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Filardo, G., Madry, H., Jelic, M. et al. Mesenchymal stem cells for the treatment of cartilage lesions: from preclinical findings to clinical application in orthopaedics. Knee Surg Sports Traumatol Arthrosc 21, 1717–1729 (2013). https://doi.org/10.1007/s00167-012-2329-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00167-012-2329-3

Keywords

Search

Navigation