Therapeutic application of mesenchymal stem cells in bone and joint diseases

Abstract

Mesenchymal stem cells (MSCs), the non-hematopoietic progenitor cells, are multi-potent stem cells from a variety of tissues with the capability of self-renewal, proliferation, differentiation into multi-lineage cell types, as well as anti-inflammatory and immunomodulatory. These properties make MSCs an ideal source of cell therapy in bone and joint diseases. This review describes the advances of animal study and preliminary clinical application in the past few years, related to MSC-based cell therapy in the common bone and joint diseases, including osteoarthritis, rheumatoid arthritis, osteoporosis, osteonecrosis of the femoral head and osteogenesis imperfecta. It highlights the promising prospect of MSC in clinical application of bone and joint diseases.

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References

  1. 1.

    Friedenstin AJ, Chailakhjan RK, Lalykina KS (1970) The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinetics 3:393–403

    Google Scholar 

  2. 2.

    da Silva ML, Chagatelles PC, Nardi NB (2006) Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J Cell Sci 119:2204–2213

    Google Scholar 

  3. 3.

    Campagnoli C, Roberts IA, Kumar S, Bennett PR, Bellantuono I, Fisk NM (2001) Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow. Blood 98:2396–2402

    CAS  PubMed  Google Scholar 

  4. 4.

    Kim JY, Jeon HB, Yang YS, Oh W, Chang JW (2010) Application of human umbilical cord blood-derived mesenchymal stem cells in disease models. World J Stem Cells 2:34–38

    PubMed Central  PubMed  Google Scholar 

  5. 5.

    Rodriguez AM, Elabd C, Amri EZ, Aihaud G, Dani C (2005) The human adipose tissue is a source of multipotent stem cells. Biochimie 87:125–128

    CAS  PubMed  Google Scholar 

  6. 6.

    Ilancheran S, Moodley Y, Manuelpillai U (2009) Human fetal membranes: a source of stem cells for tissue regeneration and repair? Placenta 30:2–10

    CAS  PubMed  Google Scholar 

  7. 7.

    Oh W, Kim DS, Yang YS, Lee JK (2008) Immunological properties of umbilical cord blood-derived mesenchymal stromal cells. Cell Immunol 251:116–123

    CAS  PubMed  Google Scholar 

  8. 8.

    Di Nicola M, Carlo-Stella C, Magni M, Milanesi M, Longoni PD, Matteucci P, Grisanti S, Gianni AM (2002) Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 99:3838–3843

    PubMed  Google Scholar 

  9. 9.

    Ren G, Su J, Zhang L, Zhao X, Ling W, L’huillie A, Zhang J, Lu Y, Roberts AI, Ji W, Zhang H, Rabson AB, Shi Y (2009) Species variation in the mechanisms of mesenchymall stem cell-mediated immunosuppression. Stem Cells 27:1954–1962

    CAS  PubMed  Google Scholar 

  10. 10.

    Beyth S, Borovsky Z, Mevorach D, Liebergall M, Gazit Z, Aslan H, Galun E, Rachmilewitz J (2005) Human mesenchymal stem cells alter antigen-presenting cell maturation and induced T-cell unresponsiveness. Blood 105:2214–2219

    CAS  PubMed  Google Scholar 

  11. 11.

    Gharbi M, Deberg M, Henrotin Y (2011) Application for proteomic techniques in studying osteoarthritis: a review. Front Physiol 2:90

    PubMed Central  PubMed  Google Scholar 

  12. 12.

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

    CAS  Google Scholar 

  13. 13.

    Aigner T, Rose J, Martin J, Buckwalter J (2004) Aging theories of primary osteoarthritis: from epidemiology to molecular biology. Rejuvenation Res 7:134–145

    CAS  PubMed  Google Scholar 

  14. 14.

    Mobasheri A (2011) Applications of proteomics to osteoarthritis, a musculoskeletal disease characterized by aging. Front Physiol 2:108

    PubMed Central  PubMed  Google Scholar 

  15. 15.

    Nöth U, Steinert AF, Tuan RS (2008) Technology Insight: adult mesenchymal stem cells for osteoarthritis therapy: delivery modes for Mesenchymal stem cells. Nat Clin Pract Rheumatol 4:371–380

    PubMed  Google Scholar 

  16. 16.

    Ameye LG, Young MF (2006) Animal models of osteoarthritis: lessons learned while seeking the ‘Holy Grail’. Curr Opin Rheumatol 18:537–547

    PubMed  Google Scholar 

  17. 17.

    Liu Y, Shu XZ, Prestwich GD (2006) Osteochondral defect repair with autologous bone marrow-derived mesenchymal stem cells in an injectable, in situ, cross-linked synthetic extracellular matrix. Tissue Eng 12:3405–3416

    CAS  PubMed  Google Scholar 

  18. 18.

    Guo X, Wang X, Zhang Y, Xia R, Hu M, Duan C (2004) Repair of large articular cartilage defects with implants of autologous mesenchymal stem cells seeded into beta-tricalcium phosphate in a sheep model. Tissue Eng 10:1818–1829

    CAS  PubMed  Google Scholar 

  19. 19.

    Hui JHP, Chen F, Thambyah A, Lee EH (2004) Treatment of chondral lesions in advanced osteochondritis dissecans: a comparative study of the efficacy of chondrocytes, mesenchymal stem cells, periosteal graft, and mosaicplasty (osteochondral autograft) in animal models. J Pediatr Orthop 24:427–433

    PubMed  Google Scholar 

  20. 20.

    Yan H, Yu C (2007) Repair of full-thickness cartilage defects with cells of different origin in a rabbit model. Arthroscopy 23:178–187

    PubMed  Google Scholar 

  21. 21.

    Kayakabe M, Tsutsumi S, Watanabe H, Kato Y, Takagishi K (2006) Transplantation of autologous rabbit BM-derived mesenchymal stromal cells embedded in hyaluronic acid gel sponge into osteochondral defects of the knee. Cytotherapy 8:343–353

    CAS  PubMed  Google Scholar 

  22. 22.

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

    CAS  PubMed  Google Scholar 

  23. 23.

    Lee KBL, Hui JHP, 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  Google Scholar 

  24. 24.

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

    PubMed  Google Scholar 

  25. 25.

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

    CAS  PubMed Central  PubMed  Google Scholar 

  26. 26.

    Sato M, Uchida K, Nakajima H, Miyazaki T, Guerrero AR, Watanabe S, Roberts S, Baba H (2012) Direct transplantation of mesenchymal stem cells into the knee joints of Hartley Strain guinea pig with spontaneous osteoarthritis. Arthritis Res Ther 14:R31

    CAS  PubMed Central  PubMed  Google Scholar 

  27. 27.

    Horie M, Sekiya I, Muneta T, Ichinose S, Matsumoto K, Saito H, Murakami T, Kobayashi E (2009) Intra-articular injected synovial stem cells differentiate into meniscal cells directly and promote meniscal regeneration without mobilization of distant organs in rat massive meniscal defect. Stem Cells 27:878–887

    CAS  PubMed  Google Scholar 

  28. 28.

    Fan J, Varshney RR, Ren L, Cai D, Wang DA (2009) Synovium-derived mesenchymal stem cells: a new cell source for musculoskeletal regeneration. Tissue Eng Part B Rev 15:75–86

    CAS  PubMed  Google Scholar 

  29. 29.

    Koga H, Shimaya M, Muneta T, Nimura A, Morito T, Hayashi M, Suzuki S, Ju YJ, Mochizuki T, Sekiya I (2008) Local adherent technique for transplanting mesenchymal stem cells as a potential treatment of cartilage defect. Arthritis Res Ther 10:R84

    PubMed Central  PubMed  Google Scholar 

  30. 30.

    Vishnubalaji R, Al-Nbaheen M, Kadalmani B, Aldahmash A, Ramesh T (2012) Comparative investigation of the differentiation capability of bone-marrow-and adipose-derived mesenchymal stem cells by qualitative and quantitative analysis. Cell Tissue Res 347:419–427

    PubMed  Google Scholar 

  31. 31.

    Guilak F, Awad HA, Fermor B, Leddy HA, Gimble JM (2004) Adipose-derived adult stem cells for cartilage tissue engineering. Biorheology 41:389–399

    CAS  PubMed  Google Scholar 

  32. 32.

    Black LL, Gaynor J, Gahring D, Adams C, Aron D, Harman S, Gingerich DA, Harman R (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. Veterinary Therapeutics 8:272–284

    PubMed  Google Scholar 

  33. 33.

    Black LL, Gaynor J, Adams C, Dhupa S, Sams AE, Taylor R, Harman S, Gingerich DA, Harman R (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 

  34. 34.

    Hou T, Xu J, Wu X, Xie Z, Luo F, Zhang Z, Zeng L (2009) Umbilical cord Wharton’s Jelly: a new potential cell source of mesenchymal stomal cells for bone tissue engineering. Tissue Eng Part A 15:2325–2334

    CAS  PubMed  Google Scholar 

  35. 35.

    Fan CG, Zhang QJ, Zhou JR (2011) Therapeutic potentials of mesenchymal stem cells derived from human umbilical cord. Stem Cell Rev 7:195–207

    PubMed  Google Scholar 

  36. 36.

    Wang L, Tran I, Seshareddy K, Weiss ML, Detamore MS (2009) A comparison of human bone marrow-derived mesenchymal stem cells and human umbilical cord-derived mesenchymal stromal cells for cartilage tissue engineering. Tissue Eng Part A 15:2259–2266

    CAS  PubMed  Google Scholar 

  37. 37.

    Fong CY, Subramanian A, Gauthaman K, Venugopal J, Biswas A, Ramakrishna S, Bongso A (2012) Human umbilical cord Whaton’s Jelly stem cells undergo enhanced chondrogenic differentiation when grown on nanofibrous scaffolds and in a sequential two-stage culture medium environment. Stem Cell Rev 8:195–209

    CAS  PubMed  Google Scholar 

  38. 38.

    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

    CAS  PubMed  Google Scholar 

  39. 39.

    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 knee. Osteoarthritis Cartilage 10:199–206

    CAS  PubMed  Google Scholar 

  40. 40.

    Ohgushi H, Kotobuki N, Funaoka H, Machida H, Hirose M, Tanaka Y, Takakura Y (2005) Tissue engineered ceramic artificial joint-ex vivo osteogenic differentiation of patient mesenchymal cells on total ankle joints for treatment of osteoarthritis. Biomaterials 26:4654–4661

    CAS  PubMed  Google Scholar 

  41. 41.

    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

    PubMed Central  PubMed  Google Scholar 

  42. 42.

    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 

  43. 43.

    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  Google Scholar 

  44. 44.

    Fournier C (2005) Where do T cells stand in rheumatoid arthritis? Joint Bone Spine 72:527–532

    PubMed  Google Scholar 

  45. 45.

    Firestein GS (2003) Evolving concepts of rheumatoid arthritis. Nature 423:356–361

    CAS  PubMed  Google Scholar 

  46. 46.

    Gonzalez MA, Gonzalez-Rey E, Rico L, Buscher D, Delgado M (2009) Treatment of experimental arthritis by inducing immune tolerance with human adipose-derived mesenchymal stem cells. Arthritis Rheum 60:1006–1019

    CAS  PubMed  Google Scholar 

  47. 47.

    Fox DA (1997) The role of T cells in the immunopathogenesis of rheumatoid arthritis: new perspectives. Arthritis Rheum 40:598–609

    CAS  PubMed  Google Scholar 

  48. 48.

    Ren G, Zhang L, Zhao X, Xu G, Zhang Y, Roberts AI, Zhao RC, Shi Y (2008) Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell 2:141–150

    CAS  PubMed  Google Scholar 

  49. 49.

    MacDonal GI, Augello A, De Bari C (2011) Role of mesenchymal stem cells in reestablishing immunologic tolerance in autoimmune rheumatic diseases. Arthritis Rheum 63(9):2547–2557

    Google Scholar 

  50. 50.

    Djouad F, Fritz V, Apparailly F, Louis-Plence P, Bony C, Sany J, Jorgensen C, Noel D (2005) Reversal of the immunosuppressive properties of mesenchymal stem cells by tumor necrosis factor alpha in collagen-induced arthritis. Arthritis Rheum 52:1595–1603

    CAS  PubMed  Google Scholar 

  51. 51.

    Schurgers E, Kelchtermans H, Mitera T, Geboes L, Matthys P (2010) Discrepancy between the in vitro and in vivo effect of murine mesenchymal stem cells on T-cell proliferation and collagen-induced arthritis. Arthritis Res Therapy 12:R31

    Google Scholar 

  52. 52.

    Chen B, Hu J, Liao L (2010) Flk-1 + mesenchymal stem cells aggravate collagen-induced arthritis by up-regulating interleukin-6. Clin Exp Immunol 159:292–302

    CAS  PubMed Central  PubMed  Google Scholar 

  53. 53.

    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

    CAS  PubMed  Google Scholar 

  54. 54.

    GonZalez MA, Gonzalez-Rey E, Rico L, Buscher D, Delgado M (2009) Treatment of experimental arthritis by inducing immune tolerance with human adipose-derived mesenchymal stem cells. Arthritis Rheum 60:1006–1019

    CAS  PubMed  Google Scholar 

  55. 55.

    Gonzalez-Rey E, Gonzalez MA, Varela N, O’Valle F, Hernandez-Cortes P, Rico L, Buscher D, Delgado M (2010) Human adipose-derived mesenchymal stem cells reduce inflammatory and T cell responses and induce regulatory T cells in vitro in rheumatoid arthritis. Ann Rheum Dis 69:241–248

    CAS  PubMed  Google Scholar 

  56. 56.

    Zhou B, Yuan J, Zhou Y, Ghawji M Jr, Deng YP, Lee AJ, Lee AJ, Nair U, Kang AH, Brand DD, Yoo TJ (2011) Administering human adipose-derived stem cells to prevent and treat experimental arthritis. Clin Immunol 141:328–337

    CAS  PubMed  Google Scholar 

  57. 57.

    Liu Y, Mu R, Wang S, Long L, Liu X, Li R, Sun J, Guo J, Zhang X, Guo J, Yu P, Li C, Liu X, Huang Z, Wang D, Li H, Gu Z, Liu B, Li Z (2010) Therapeutic potential of human umbilical cord mesenchymal stem cells in the treatment of rheumatoid arthritis. Arthritis Res Ther 12:R210

    PubMed Central  PubMed  Google Scholar 

  58. 58.

    Choi JJ, Yoo SA, Park SJ, Kang YJ, Kim WU, Oh IH, Cho CS (2008) Mesenchymal stem cells overexpressing interleukin-10 attenuate collagen-induced arthritis in mice. Clin Exp Immunol 153:269–276

    CAS  PubMed Central  PubMed  Google Scholar 

  59. 59.

    Park MJ, Park HS, Cho ML, Oh HJ, Cho YG, Min SY, Chung BH, Lee JW, Kim HY, Cho SG (2011) Transforming growth factor β-transduced mesenchymal stem cells ameliorate experimental autoimmune arthritis through reciprocal regulation of Treg/Th17 cells and osteoclastogenesis. Arthritis Rheum 63:1668–1680

    CAS  PubMed  Google Scholar 

  60. 60.

    Ra JC, Kang SK, Shin IS, Park HG, Joo SA, Kim JG, Kang BC, Lee YS, Nakama K, Piao M, Sohl B, Kurtz A (2011) Stem cell treatment for patients with autoimmune disease by systemic infusion of culture-expanded autologous adipose tissue derived mesenchymal stem cells. J Transl Med 9:181

    PubMed Central  PubMed  Google Scholar 

  61. 61.

    Liang J, Li X, Zhang H, Wang D, Feng X, Wang H, Hua B, Liu B, Sun L (2012) Allogeneic mesenchymal stem cells transplantation in patients with refractory RA. Clin Rheumatol 31:157–161

    PubMed  Google Scholar 

  62. 62.

    Peng KY, Horing LY, Sung HC, Huang HC, Wu RT (2011) Antiosteoporotic activity of dioscorea alata L.cv. Phyto through driving mesenchymal stem cells differentiation for bone formation. Evid Based Complement Alternat Med 2011:712892

    PubMed Central  PubMed  Google Scholar 

  63. 63.

    Raisz LA (2005) Pathogenies of osteoporosis: concepts, conflicts, and prospects. J Clin Invest 115:3318–3325

    CAS  PubMed Central  PubMed  Google Scholar 

  64. 64.

    Wang Z, Goh J, De Das S, Ge Z, Ouyang H, Chong JS, Low SL, Lee EH (2006) Efficacy of bone marrow-derived stem cells in strengthening osteoporotic bone in a rabbit model. Tissue Eng 12:1753–1761

    CAS  PubMed  Google Scholar 

  65. 65.

    Turgeman G, Aslan H, Gazit Z, Gazit D (2002) Cell-mediated gene therapy for bone formation and regeneration. Curr Opin Mol Ther 4:390–394

    CAS  PubMed  Google Scholar 

  66. 66.

    Bruder SP, Fink DJ, Caplan AI (1994) Mesenchymal stem cells in bone development, bone repair, and skeletal regeneration therapy. J Cell Biochem 56:283–294

    CAS  PubMed  Google Scholar 

  67. 67.

    Nuttall ME, Patton AJ, Olivera DJ, Nadeau DP, Gowen M (1998) Human trabecular bone cells are able to express both osteoblastic and adipocytic phenotype: implications for osteopenic disorders. J Bone Miner Res 13:371–382

    CAS  PubMed  Google Scholar 

  68. 68.

    Turgeman G, Zilberman Y, Zhou S, Kelly P, Moutsatsos IK, Kharode YP, Borella LE, Bex FJ, Komm BS, Bodine PV, Gazit D (2002) Systemically administered rh BMP-2 promotes MSC activity and reverses bone and cartilage loss in osteopenic mice. J Cell Biochem 86:461–474

    CAS  PubMed  Google Scholar 

  69. 69.

    Zhou S, Zilberman Y, Wassermann K, Bain SD, Sadovsky Y, Gazit D (2001) Estrogen modulates estrogen receptor alpha and beta expression, osteogenic activity, and apoptosis in mesenchymal stem cells (MSCs) of osteoporotic mice. J Cell Biochem Suppl 36(Suppl):144–155

    PubMed  Google Scholar 

  70. 70.

    Ocarino Nde M, Boeloni JN, Jorgetti V, Gomes DA, Goes AM, Serakides R (2010) Intra-bone marrow injection of mesenchymal stem cells improves the femur bone mass of osteoporotic female rats. Connect Tissue Res 51:426–433

    PubMed  Google Scholar 

  71. 71.

    Egermann M, Gerhardt C, Barth A, Maestroni GJ, Schnerder E, Alini M (2011) Pinealectomy affects bone mineral density and structure-an experimental study in sheep. BMC Musculoskelet Disord 12:271

    PubMed Central  PubMed  Google Scholar 

  72. 72.

    Jerome C, Missbach M, Gamse R (2011) Balicatib, a cathepsin K inhibitor, stimulates periosteal bone formation in monkeys. Osteoporos Int 22:3001–3011

    CAS  PubMed  Google Scholar 

  73. 73.

    Tang YC, Tang W, Tian WD, Chen XZ, Li SW (2006) A study on repairing mandibular defect by means of tissue-engineering and human bone morphogenetic protein-2 gene transfection in osteoporotic rats. Zhonghua Kou Qiang Yi Xue Za Zhi 41:430–431

    PubMed  Google Scholar 

  74. 74.

    Hsiao FS, Cheng CC, Peng SY, Huang HY, Lian WS, Jan ML, Fang YT, Cheng EC, Lee KH, Cheng WT, Lin SP, Wu SC (2010) Isolation of therapeutically functional mouse bone marrow mesenchymal stem cells within 3 h by an effective single-step plastic-adherent method. Cell Prolif 43:235–248

    CAS  PubMed  Google Scholar 

  75. 75.

    Bianco P, Riminucci M, Gronthos S, Robey PG (2001) Bone marrow stromal stem cells: nature, biology, and potential applications. Stem Cells 19:180–192

    CAS  PubMed  Google Scholar 

  76. 76.

    Kanakaris NK, Petsatodis G, Tagil M, Giannoudis PV (2009) Is there a role for bone morphogenetic proteins in osteoporotic fractures? Injury 40(Suppl 3):S21–S26

    PubMed  Google Scholar 

  77. 77.

    Turgeman G, Pittman DD, Muller R, Kurkalli BG, Zhou S, Pelled G, Peyser A, Ziberman Y, Moutsatsos IK, Gazit D (2001) Engineered human mesenchymal stem cells: a novel platform for skeletal cell mediated gene therapy. J Gene Med 3:240–251

    CAS  PubMed  Google Scholar 

  78. 78.

    Egermann M, Baltzer AW, Adamaszek S, Evans C, Robbins P, Schneider E, Lill CA (2006) Direct adenoviral transfer of bone morphogenetic protein-2 cDNA enhances fracture healing in osteoporotic sheep. Hum Gene Ther 17:507–517

    CAS  PubMed  Google Scholar 

  79. 79.

    Kumar S, Mahendra G, Nagy TR, Ponnazhagan S (2004) Osteogenic differentiation of recombinant adeno-associated virus 2-transduced murine mesenchymal stem cells and development of an immunocompetent mouse model for ex vivo osteoporosis gene therapy. Hum Gene Ther 15:1197–1206

    CAS  PubMed  Google Scholar 

  80. 80.

    Zhang XS, Linkhart TA, Chen ST, Peng H, Wergedal JE, Guttierez GG, Sheng MH, Lau KH, Baylink DJ (2004) Local ex vivo gene therapy with bone marrow stromal cells expressing human BMP4 promotes endosteal bone formation in mice. J Gene Med 6:4–15

    CAS  PubMed  Google Scholar 

  81. 81.

    Hu J, Qi MC, Zou SJ, Li JH, Luo E (2007) Callus formation enhanced by BMP-7 ex vivo gene therapy during distraction osteogenesis in rats. J Orthop Res 25:241–251

    CAS  PubMed  Google Scholar 

  82. 82.

    Dumon RJ, Dyoub H, Li JZ, Dumont AS, Kallmes DF, Hankins GR, Helm GA (2002) Ex vivo bone morphogenetic protein-9 gene therapy using human mesenchymal stem cells induces spinal fusion in rodents. Neurosurgery 51:1239–1245

    Google Scholar 

  83. 83.

    Kim D, Cho SW, Her SJ, Yang JY, Kim SW, Kim SY, Shin CS (2006) Retrovirus-mediated gene transfer of receptor activator of nuclear factor-kappaB-Fc prevents bone loss in ovariectomized mice. Stem Cells 24:1798–1805

    CAS  PubMed  Google Scholar 

  84. 84.

    Cho SW, Sun HJ, Yang JY, Jung JY, An JH, Cho HY, Choi HJ, Kim SW, Kim SY, Kim D, Shin CS (2009) Transplantation of mesenchymal stem cells overexpressing RANK-Fc or CXCR4 prevents bone loss in ovariectomized mice. Mol Ther 17:1979–1987

    CAS  PubMed  Google Scholar 

  85. 85.

    Lien CY, Chih-Yuan Ho K, Lee OK, Blunn GW, Su Y (2009) Restoration of bone mass and strength in glucocorticoid-treated mice by systemic transplantation of CXCR4 and cbfa-1 co-expressing mesenchymal stem cells. J Bone Miner Res 24:837–848

    CAS  PubMed  Google Scholar 

  86. 86.

    Chen HT, Lee MJ, Chen CH et al (2012) Proliferation and differentiation potential of human adipose-derived mesenchymal stem cells isolated from elderly patients with osteoporotic fractures. J Cell Mol Med 16:582–593

    CAS  PubMed  Google Scholar 

  87. 87.

    Wang CJ, Wang FS, Huang CC, Yang KD, Weng LH, Huang HY (2005) Treatment for osteonecrosis of the femoral head: comparison of extracorporeal shock waves with core decompression and bone-grafting. J Bone Joint Surg Am 87:2380–2387

    PubMed  Google Scholar 

  88. 88.

    Feitosa ML, Fadel L, Beltrao-Braga PC et al (2010) Successful transplant of mesenchymal stem cells in induced osteonecrosis of the ovine femoral head: preliminary results. Acta Cir Bras 25:416–422

    PubMed  Google Scholar 

  89. 89.

    Chan TW, Dalinka MK, Steinberg ME, Kressel HY (1991) MRI appearance of femoral head osteonecrosis following core decompression and bone grafting. Skeletal Radiol 20:103–107

    CAS  PubMed  Google Scholar 

  90. 90.

    Wassenaar RP, Verburg H, Taconis WK, van der Eijken JW (1996) Avascular osteonecrosis of the femoral head treated with a vascularized iliac bone graft: preliminary results and follow-up with radiography and MR imaging. Radiographics 16:585–594

    CAS  PubMed  Google Scholar 

  91. 91.

    Hernigou P, Beaujean F (2002) Treatment of osteonecrosis with autologous bone marrow grafting. Clin Orthop 405:14–23

    PubMed  Google Scholar 

  92. 92.

    Hernigou P, Manicom O, Poignard A et al (2004) Core decompression with marrow stem cells. Operative Tech Orthop 14:68–74

    Google Scholar 

  93. 93.

    Gangji V, Hauzeur JP, Matos C, De Maertelaer V, Toungouz M, Lambermont M (2004) Treatment of osteonecrosis of the femoral head with implantation of autologous bone-marrow cells. A pilot study. J Bone Joint Surg Am 86-A:1153–1160

    PubMed  Google Scholar 

  94. 94.

    Wang BL, Sun W, Shi ZC et al (2010) Treatment of nontraumatic osteonecrosis of the femoral head with the implantation of core decompression and concentrated autologous bone marrow containing mononuclear cells. Arch Orthop Trauma Surg 130:859–865

    PubMed  Google Scholar 

  95. 95.

    Hernigou P, Poignard A, Zilber S, Rouard H (2009) Cell therapy of hip osteonecrosis with autologous bone marrow grafting. Indian J Orthop 43:40–45

    PubMed Central  PubMed  Google Scholar 

  96. 96.

    GangJi V, De Maertelaer V, Hauzeur JP (2011) Autologous bone marrow cell implantation in the treatment of non-traumatic osteonecrosis of the femoral head: five year follow-up of a prospective controlled study. Bone 49:1005–1009

    PubMed  Google Scholar 

  97. 97.

    Hernigou P (1998) Growth factors released from bone marrow are promising tools in orthopedic surgery. Rev Rhum Engl Ed 65:79–84

    CAS  PubMed  Google Scholar 

  98. 98.

    Noel D, Djouad F, Jorgense C (2002) Regenerative medicine through mesenchymal stem cells for bone and cartilage repair. Curr Opin Investig Drugs 3:1000–1004

    PubMed  Google Scholar 

  99. 99.

    Kuo TK, Ho JH, Lee OK (2009) Mesenchymal stem cell therapy for nonmusculoskeletal diseases: emerging applications. Cell Transplant 18:1013–1028

    PubMed  Google Scholar 

  100. 100.

    Cui Q, Xiao Z, Li X, Saleh KJ, Balian G (2006) Use of genetically engineered bone-marrow stem cells to treat femoral defects: an experimental study. J Bone Joint Surg Am 88(Suppl 3):167–172

    PubMed  Google Scholar 

  101. 101.

    Matsuya H, Kushida T, Asada T, Umeda M, Wada T, Iida H (2008) Regenerative effects of transplanting autologous mesenchymal stem cells on corticosteroid-induced osteonecrosis in rabbits. Mod Rhheumatol 18:132–139

    Google Scholar 

  102. 102.

    Li ZH, Liao W, Cui XL et al (2011) Intravenous transplantation of allogeneic bone marrow mesenchymal stem cells and its directional migration to the necrotic femoral head. Int J Med Sci 8:74–83

    PubMed Central  PubMed  Google Scholar 

  103. 103.

    Yan Z, Hang D, Guo C, Chen Z (2009) Fate of mesenchymal stem cells transplanted to osteonecrosis of femoral head. J Orthop Res 27:442–446

    PubMed  Google Scholar 

  104. 104.

    Peng J, Wen C, Wang A et al (2011) Micro-CT-based bone ceramic scaffolding and its performance after seeding with mesenchymal stem cells for repair of load-bearing bone defect in canine femoral head. J Biomed Mater Res B Appl Biomater 96:316–325

    PubMed  Google Scholar 

  105. 105.

    Feitosa ML, Fadel L, Beltrao-Braga PC et al (2010) Successful transplant of mesenchymal stem cells in induced osteonecrosis of the ovine femoral head: preliminary results. Acta Cir Bras 25:416–422

    PubMed  Google Scholar 

  106. 106.

    Yang J, Wang L, Xu Y, Wang J, Wang Y (2008) An experimental study on treatment of steroid-associated femoral head necrosis with simvastatin and BMSCs transplantation. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 22:290–294

    CAS  PubMed  Google Scholar 

  107. 107.

    Wen Q, Zhou L, Zhou C, Zhou M, Luo W, Ma L (2012) Change in hepatocyte growth factor concentration promote mesenchymal stem cell-mediated osteogenic regeneration. J Cell Mol Med 16:1260–1273

    CAS  PubMed  Google Scholar 

  108. 108.

    Liu BY, Zhao DW (2009) Treatment for osteonecrosis of femoral head by hVEGF-165 gene modified marrow stromal stem cells under arthroscope. Zhonghua Yi Xue Za Zhi 89:2629–2633

    CAS  PubMed  Google Scholar 

  109. 109.

    Zhang C, Wang KZ, Qiang H et al (2010) Angiopoiesis and bone regeneration via co-expression of the hVEGF and hBMP genes from an adeno-associated viral vector in vitro and in vivo. Acta Pharmacol Sin 31:821–830

    CAS  PubMed  Google Scholar 

  110. 110.

    Shi ZB, Wang KZ (2010) Effects of recombinant adeno-associated viral vectors on angiopoiesis and osteogenesis in cultured rabbit bone marrow stem cells via co-expressing hVEGF and hBMP genes: a preliminary study in vitro. Tissue Cell 42:314–321

    CAS  PubMed  Google Scholar 

  111. 111.

    Zhang C, Ma Q, Qiang H, Li M, Dang X, Wang K (2010) Study on effect of recombinant adeno-associated virus co-expressing human vascular endothelial growth factor 165 and human bone morphogenetic protein 7 genes on bone regeneration and angiopoiesis in vivo. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 24:1449–1454

    CAS  PubMed  Google Scholar 

  112. 112.

    Tang TT, Lu B, Yue B et al (2007) Treatment of osteonecrosis of the femoral head with hBMP-2-gene-modified tissue-engineered bone in goats. J Bone Joint Surg Br 89:127–129

    CAS  PubMed  Google Scholar 

  113. 113.

    Xiao ZM, Jiang H, Zhan XL, Wu ZG, Zhang XL (2008) Treatment of osteonecrosis of femoral head with BMSCs-seeded bio-derived bone materials combined with rhBMP-2 in rabbits. Chin J Traumatol 11:165–170

    CAS  PubMed  Google Scholar 

  114. 114.

    Chang T, Tang K, Tao X et al (2010) Treatment of early avascular necrosis of femoral head by core decompression combined with autologous bone marrow mesenchymal stem cells transplantation. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 24:739–743

    PubMed  Google Scholar 

  115. 115.

    Zhao D, Cui D, Wang B et al (2012) Treatment of early stage osteonecrosis of the femoral head with autologous implantation of bone marrow-derived and cultured mesenchymal stem cells. Bone 50:325–330

    PubMed  Google Scholar 

  116. 116.

    Pak J (2012) Autologous adipose tissue-derived stem cells induce persistent bone-like tissue in osteonecrotic femoral heads. Pain Physician 15:75–85

    PubMed  Google Scholar 

  117. 117.

    Byers PH, Wallis GA, Willing MC (1991) Osteogenesis imperfecta: translation of mutation to phenotype. J Med Genet 28:433–442

    CAS  PubMed  Google Scholar 

  118. 118.

    Cabral WA, Marini JC (2004) High proportion of mutant osteoblasts is compatible with normal skeletal function in mosaic carriers of osteogenesis imperfecta. Am J Hum Genet 74:752–760

    CAS  PubMed Central  PubMed  Google Scholar 

  119. 119.

    Millington-Ward S, Allers C, Tuohy G et al (2002) Validation in mesenchymal progenitor cells of a mutation-independent ex vivo approach to gene therapy for osteogenesis imperfecta. Hum Mol Gent 11:2201–2206

    CAS  Google Scholar 

  120. 120.

    Caplan AI (1995) Osteogenesis imperfecta, rehabilitation medicine, fundamental research and mesenchymal stem cells. Connect Tissue Res 31:S9–S14

    CAS  PubMed  Google Scholar 

  121. 121.

    Pereira RF, O’Hara MD, Laptev AV et al (1998) Marrow stromal cells as a source of progenitor cells for nonhematopoietic tissues in transgenic mice with a phenotype of osteogenesis imperfecta. Pro Natl Acad Sci USA 95:1142–1147

    CAS  Google Scholar 

  122. 122.

    Guillot PV, Abass O, Bassett JH et al (2008) Intrauterine transplantation of human fetal mesenchymal stem cells from first-trimester blood repairs bone and reduces fractures in osteogenesis imperfecta mice. Blood 111:1717–1725

    CAS  PubMed  Google Scholar 

  123. 123.

    Horwitz EM, Prockop DJ, Fitzpatrick LA et al (1999) Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nat Med 5:309–313

    CAS  PubMed  Google Scholar 

  124. 124.

    Horwitz EM, Prockop DJ, Gordon PL et al (2001) Clinical responses to bone marrow transplantation in children with severe osteogenesis imperfecta. Blood 97:1227–1231

    CAS  PubMed  Google Scholar 

  125. 125.

    Horwitz EM, Gordon PL, Koo WK et al (2002) Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: implications for cell therapy of bone. Proc Natl Acad Sci USA 99:8932–8937

    CAS  PubMed  Google Scholar 

  126. 126.

    Le Blanc K, Gotherstrom C, Ringden O et al (2005) Fetal mesenchymal stem-cell engraftment in bone after in utero transplantation in a patients with severe osteogenesis imperfecta. Transplantation 79:1607–1614

    PubMed  Google Scholar 

  127. 127.

    Millington-Ward S, McMahon HP, Allen D et al (2004) RNAi of COL1A1 in mesenchymal progenitor cells. Eur J Hum Genet 12:864–866

    CAS  PubMed  Google Scholar 

  128. 128.

    Ljunggren O, Lindahl K, Rubin CJ, Kindmark A (2011) Allele-specific gene silencing in osteogenesis imperfecta. Endocr Dev 21:85–90

    CAS  PubMed  Google Scholar 

  129. 129.

    Jaganathan BG, Bonnet D (2012) Human mesenchymal stromal cells senesce with exogenous OCT4. Cytotherapy 14:1054–1063

    CAS  PubMed  Google Scholar 

  130. 130.

    Symonds CE, Galderisi U, Giordano A (2009) Aging of the inceptive cellular population: the relationship between stem cells and aging. Aging (Albany NY) 1:372–381

    CAS  Google Scholar 

  131. 131.

    Galderisi U, Helmbold H, Squillaro T, Alessio N, Komm N, Khadang B, Cipollaro M, Bohn W, Giordano A (2009) In vitro senescence of rat mesenchymal stem cell is accompanied by downregulation of stemness-related and DNA damage repair genes. Stem Cells Dev 18:1033–1042

    CAS  PubMed  Google Scholar 

  132. 132.

    Liu TM, Ng WM, Tan HS, Vinitha D, Yang Z, Fan JB, Zou Y, Hui JH, Lee EH, Lim B (2012) Molecular basis of immortalization of human mesenchymal stem cells by combination of p53 knockdown and human telomerase reverse transcriptase overexpression. Stem Cells Dev Aug 21 [Epub ahead of print]

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Acknowledgments

This work was supported by the Key Project for Drug Research and Development from the Ministry of Science and Technology of China (2010ZX09401-302-5-07). The authors thank Professor Zhongchao Han in National Research Center for Stem Cell Engineering and Technology for critical reading of the manuscript.

Conflict of interest

The funder has no role in study design and the manuscript preparation. All authors indicate no actual and potential conflicts of interest.

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Correspondence to Jinxiang Han.

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Liu, Y., Wu, J., Zhu, Y. et al. Therapeutic application of mesenchymal stem cells in bone and joint diseases. Clin Exp Med 14, 13–24 (2014). https://doi.org/10.1007/s10238-012-0218-1

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Keywords

  • Mesenchymal stem cells (MSCs)
  • Osteoarthritis (OA)
  • Osteogenesis imperfecta (OI)
  • Osteoporosis
  • Osteonecrosis of the femoral head (ONFH)
  • Rheumatoid arthritis (RA)