Mesenchymal stem cells in connective tissue engineering and regenerative medicine: Applications in cartilage repair and osteoarthritis therapy

Histology and Histopathology

Volumn 24, Issue 3, 2009, Pages 347-366

  Mobasheri, Ali ^a   Csaki, C ^b   Clutterbuck, A L ^a   Rahmanzadeh, M ^c   Shakibaei, M ^b  

^a UNIVERSITY OF NOTTINGHAM   (United Kingdom)

^b UNIVERSITY OF MUNICH   (Germany)

^c Joint Surgery Centre Berlin   (Germany)

Author keywords

Articular cartilage; Autologous chondrocyte transplantation; Mesenchymal stem cell; Mosaicplasty; Osteoarthritis; Regenerative medicine; Tissue engineering

Indexed keywords

TISSUE SCAFFOLD;

AGING; BONE ATROPHY; BONE INJURY; CARTILAGE BIOPSY; CARTILAGE CELL; CELL DIFFERENTIATION; CELL EXPANSION; CELL ISOLATION; CHONDROCYTE IMPLANTATION; CHONDROGENESIS; CONNECTIVE TISSUE; EXPERIMENTAL MODEL; HUMAN; IN VITRO STUDY; MESENCHYMAL STEM CELL TRANSPLANTATION; MICROFRACTURE; MONOLAYER CULTURE; MOSAICPLASTY; NONHUMAN; OSTEOARTHRITIS; REGENERATIVE MEDICINE; REVIEW; SURGICAL TECHNIQUE; TISSUE ENGINEERING; TISSUE REPAIR; TREATMENT OUTCOME; WEIGHT BEARING; AGED; ARTICULAR CARTILAGE; BIOLOGICAL MODEL; CYTOLOGY; MESENCHYMAL STEM CELL; METHODOLOGY; PATHOLOGY;

ANIMALIA;

AGED; CARTILAGE, ARTICULAR; CONNECTIVE TISSUE; HUMANS; MESENCHYMAL STEM CELL TRANSPLANTATION; MESENCHYMAL STEM CELLS; MODELS, BIOLOGICAL; OSTEOARTHRITIS; REGENERATIVE MEDICINE; TISSUE ENGINEERING;

EID: 63649120787     PISSN: 02133911     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (185)

1. Abramson S.B., Attur M. and Yazici Y. (2006). Prospects for disease modification in osteoarthritis. Nat. Clin. Pract. Rheumatol. 2, 304-312.
2. Ahmed I.M., Lagopoulos M., McConnell P., Soames R.W. and Sefton G.K. (1998). Blood supply of the Achilles tendon. J. Orthop. Res. 16, 591-596.
3. Ahsan T., Lottman L.M., Harwood F., Amiel D. and Sah R.L. (1999). Integrative cartilage repair: inhibition by beta-aminopropionitrile. J. Orthop. Res. 17, 850-857.
4. Alexanian A.R. and Sieber-Blum M. (2003). Differentiating adult hippocampal stem cells into neural crest derivatives. Neuroscience 118, 1-5.
5. Anderer U. and Libera J. (2002). In vitro engineering of human autogenous cartilage. J. Bone Miner. Res. 17, 1420-1429.
6. Aoki M., Yasutake M. and Murohara T. (2004). Derivation of functional endothelial progenitor cells from human umbilical cord blood mononuclear cells isolated by a novel cell filtration device. Stem Cells 22, 994-1002.
7. Arinzeh T.L. (2005). Mesenchymal stem cells for bone repair: preclinical studies and potential orthopedic applications. Foot Ankle Clin. 10, 651-665, viii.
8. Aulthouse A.L. and Solursh M. (1987). The detection of a precartilage, blastema-specific marker. Dev. Biol. 120, 377-384.
9. Barbero A., Ploegert S., Heberer M. and Martin I. (2003). Plasticity of clonal populations of dedifferentiated adult human articular chondrocytes. Arthritis Rheum. 48, 1315-1325.
10. Barry F.P. and Murphy J.M. (2004). Mesenchymal stem cells: clinical applications and biological characterization. Int. J. Biochem. Cell Biol. 36, 568-584.
11. Barry F., Boynton R.E., Liu B. and Murphy J.M. (2001). Chondrogenic differentiation of mesenchymal stem cells from bone marrow: differentiation-dependent gene expression of matrix components. Exp. Cell Res. 268, 189-200.
12. Beris A.E., Lykissas M.G., Papageorgiou C.D. and Georgoulis A.D. (2005). Advances in articular cartilage repair. Injury 36 (Suppl 4), S14-23.
13. Bieback K., Kern S., Kluter H. and Eichler H. (2004). Critical parameters for the isolation of mesenchymal stem cells from umbilical cord blood. Stem Cells 22, 625-634.
14. Bodo G., Hangody L., Szabo Z., Peham C., Schinzel M., Girtler D. and Sotonyi P. (2000). Arthroscopic autologous osteochondral mosaicplasty for the treatment of subchondral cystic lesion in the medial femoral condyle in a horse. Acta Vet. Hung. 48, 343-354.
15. Bora F.W. Jr. and Miller G. (1987). Joint physiology, cartilage metabolism, and the etiology of osteoarthritis. Hand Clin. 3, 325-336.
16. Bosnakovski D., Mizuno M., Kim G., Takagi S., Okumura M. and Fujinaga T. (2005). Isolation and multilineage differentiation of bovine bone marrow mesenchymal stem cells. Cell Tissue Res. 319, 243-253.
17. Bottai D., Fiocco R., Gelain F., Defilippis L., Galli R., Gritti A. and Vescovi L.A. (2003). Neural stem cells in the adult nervous system. J. Hematother. Stem Cell Res. 12, 655-670.
18. Breinan H.A., Minas T., Hsu H.P., Nehrer S., Sledge C.B. and Spector M. (1997). Effect of cultured autologous chondrocytes on repair of chondral defects in a canine model. J. Bone Joint Surg. Am. 79, 1439-1451.
19. Brittberg M. (1999). Autologous chondrocyte transplantation. Clin. Orthop. Relat. Res. S147-155.
20. Brittberg M. (2008). Autologous chondrocyte implantation - technique and long-term follow-up. Injury 39 (Suppl 1), S40-49.
21. Brittberg M., Lindahl A., Nilsson A., Ohlsson C., Isaksson O. and Peterson L. (1994). Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N. Engl. J. Med. 331, 889-895.
22. Brittberg M., Nilsson A., Lindahl A., Ohlsson C. and Peterson L. (1996). Rabbit articular cartilage defects treated with autologous cultured chondrocytes. Clin. Orthop. Relat. Res. 270-283.
23. Brittberg M., Peterson L., Sjogren-Jansson E., Tallheden T. and Lindahl A. (2003). Articular cartilage engineering with autologous chondrocyte transplantation. A review of recent developments. J. Bone Joint Surg. Am. 85-A Suppl 3, 109-115.
24. Brooks P.M. (2006). The burden of musculoskeletal disease - a global perspective. Clin. Rheumatol. 25, 778-781.
25. Broussard J.S. Jr. (2005). Derangement, osteoarthritis, and rheumatoid arthritis of the temporomandibular joint: implications, diagnosis, and management. Dent. Clin. North Am. 49, 327-342.
26. Buckwalter J.A. and Martin J.A. (2006). Osteoarthritis. Adv. Drug Deliv. Rev. 58, 150-167.
27. Cancedda R., Descalzi Cancedda F. and Castagnola P. (1995). Chondrocyte differentiation. Int. Rev. Cytol. 159, 265-358.
28. Cancedda R., Dozin B., Giannoni P. and Quarto R. (2003). Tissue engineering and cell therapy of cartilage and bone. Matrix Biol. 22, 81-91.
29. Canty E.G. and Kadler K.E. (2002). Collagen fibril biosynthesis in tendon: a review and recent insights. Comp. Biochem. Physiol. A Mol. Integr. Physiol. 133, 979-985.
30. Caplan A.I. (1991). Mesenchymal stem cells. J. Orthop. Res. 9, 641-650.
31. Caplan A.I. (2000). Tissue engineering designs for the future: new logics, old molecules. Tissue Eng. 6, 1-8.
32. Caplan A.I. (2007). Adult mesenchymal stem cells for tissue engineering versus regenerative medicine. J. Cell. Physiol. 213, 341-347.
33. Caplan A.I. and Dennis J.E. (2006). Mesenchymal stem cells as trophic mediators. J. Cell Biochem. 98, 1076-1084.
34. Caplan A.I. and Goldberg V.M. (1999). Principles of tissue engineered regeneration of skeletal tissues. Clin. Orthop. Relat. Res. 367 Suppl, S12-16.
35. Caplan A.I., Elyaderani M., Mochizuki Y., Wakitani S. and Goldberg V.M. (1997). Principles of cartilage repair and regeneration. Clin. Orthop. Relat. Res. 342, 254-269.
36. Carlberg A.L., Pucci B., Rallapalli R., Tuan R.S. and Hall D.J. (2001). Efficient chondrogenic differentiation of mesenchymal cells in micromass culture by retroviral gene transfer of BMP-2. Differentiation 67, 128-138.
37. Chiou M., Xu Y. and Longaker M.T. (2006). Mitogenic and chondrogenic effects of fibroblast growth factor-2 in adipose-derived mesenchymal cells. Biochem. Biophys. Res. Commun. 343, 644-652.
38. Chubinskaya S. and Kuettner K.E. (2003). Regulation of osteogenic proteins by chondrocytes. Int. J. Biochem. Cell Biol. 35, 1323-1340.
39. Clark K.L. (2007). Nutritional considerations in joint health. Clin. Sports Med. 26, 101-118.
40. Conget P.A. and Minguell J.J. (1999). Phenotypical and functional properties of human bone marrow mesenchymal progenitor cells. J. Cell Physiol. 181, 67-73.
41. Czitrom A.A., Langer F., McKee N. and Gross A.E. (1986). Bone and cartilage allotransplantation. A review of 14 years of research and clinical studies. Clin. Orthop. Relat. Res. 208, 141-145.
42. Darling E.M. and Athanasiou K.A. (2005). Rapid phenotypic changes in passaged articular chondrocyte subpopulations. J. Orthop. Res. 23, 425-432.
43. Day T.F., Guo X., Garrett-Beal L. and Yang Y. (2005). Wnt/beta-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis. Dev. Cell 8, 739-750.
44. De Bari C., Dell'Accio F., Tylzanowski P. and Luyten F.P. (2001). Multipotent mesenchymal stem cells from adult human synovial membrane. Arthritis Rheum. 44, 1928-1942.
45. Dell'Accio F., Vanlauwe J., Bellemans J., Neys J., De Bari C. and Luyten F.P. (2003). Expanded phenotypically stable chondrocytes persist in the repair tissue and contribute to cartilage matrix formation and structural integration in a goat model of autologous chondrocyte implantation. J. Orthop. Res. 21, 123-131.
46. Denker A.E., Haas A.R., Nicoll S.B. and Tuan R.S. (1999). Chondrogenic differentiation of murine C3H10T1/2 multipotential mesenchymal cells: I. Stimulation by bone morphogenetic protein-2 in high-density micromass cultures. Differentiation 64, 67-76.
47. Derfoul A., Perkins G.L., Hall D.J. and Tuan R.S. (2006). Glucocorticoids promote chondrogenic differentiation of adult human mesenchymal stem cells by enhancing expression of cartilage extracellular matrix genes. Stem Cells 24, 1487-1495.
48. Dominici M., Le Blanc K., Mueller I., Slaper-Cortenbach I., Marini F., Krause D., Deans R., Keating A., Prockop D. and Horwitz E. (2006). Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8, 315-317.
49. Fischer L., Boland G. and Tuan R.S. (2002a). Wnt-3A enhances bone morphogenetic protein-2-mediated chondrogenesis of murine C3H10T1/2 mesenchymal cells. J. Biol. Chem. 277, 30870-30878.
50. Fischer L., Boland G. and Tuan R.S. (2002b). Wnt signaling during BMP-2 stimulation of mesenchymal chondrogenesis. J. Cell Biochem. 84, 816-831.
51. Fortier L.A., Nixon A.J., Williams J. and Cable C.S. (1998). Isolation and chondrocytic differentiation of equine bone marrow-derived mesenchymal stem cells. Am. J. Vet. Res. 59, 1182-1187.
52. Frech T.M. and Clegg D.O. (2007). The utility of nutraceuticals in the treatment of osteoarthritis. Curr. Rheumatol. Rep. 9, 25-30.
53. Fuchs E., Tumbar T. and Guasch G. (2004). Socializing with the neighbors: stem cells and their niche. Cell 116, 769-778.
54. Gibson G.J. and Flint M.H. (1985). Type X collagen synthesis by chick sternal cartilage and its relationship to endochondral development. J. Cell Biol. 101, 277-284.
55. Goggs R., Vaughan-Thomas A., Clegg P.D., Carter S.D., Innes J.F., Mobasheri A., Shakibaei M., Schwab W. and Bondy C.A. (2005). Nutraceutical therapies for degenerative joint diseases: a critical review. Crit. Rev. Food Sci Nutr. 45, 145-164.
56. Goldring M.B. and Goldring S.R. (2007). Osteoarthritis. J. Cell Physiol. 213, 626-634.
57. Grande D.A. and Pitman M.I. (1988). The use of adhesives in chondrocyte transplantation surgery. Preliminary studies. Bull. Hosp. Jt. Dis. Orthop. Inst. 48, 140-148.
58. Grande D.A., Pitman M.I., Peterson L., Menche D. and Klein M. (1989). The repair of experimentally produced defects in rabbit articular cartilage by autologous chondrocyte transplantation. J. Orthop. Res. 7, 208-218.
59. Grigoriadis A.E., Heersche J.N. and Aubin J.E. (1988). Differentiation of muscle, fat, cartilage, and bone from progenitor cells present in a bone-derived clonal cell population: effect of dexamethasone. J. Cell Biol. 106, 2139-2151.
60. Hangody L. and Fules P. (2003). Autologous osteochondral mosaicplasty for the treatment of full-thickness defects of weight-bearing joints: ten years of experimental and clinical experience. J. Bone Joint Surg. Am. 85-A (Suppl 2), 25-32.
61. Hangody L., Feczko P., Bartha L., Bodo G. and Kish G. (2001a). Mosaicplasty for the treatment of articular defects of the knee and ankle. Clin. Orthop. Relat. Res. 391 Suppl, S328-336.
62. Hangody L., Kish G., Modis L., Szerb I., Gaspar L., Dioszegi Z. and Kendik Z. (2001b). Mosaicplasty for the treatment of osteochondritis dissecans of the talus: two to seven year results in 36 patients. Foot Ankle Int. 22, 552-558.
63. Hauselmann H.J. (2001). Nutripharmaceuticals for osteoarthritis. Best Pract. Res. Clin. Rheumatol. 15, 595-607.
64. Helder M.N., Knippenberg M., Klein-Nulend J. and Wuisman P.I. (2007). Stem cells from adipose tissue allow challenging new concepts for regenerative medicine. Tissue Eng. 13, 1799-1808.
65. Henrotin Y., Sanchez C. and Balligand M. (2005). Pharmaceutical and nutraceutical management of canine osteoarthritis: present and future perspectives. Vet. J. 170, 113-123.
66. Henson F.M., Davies M.E., Skepper J.N. and Jeffcott L.B. (1995). Localisation of alkaline phosphatase in equine growth cartilage. J. Anat. 187 (Pt 1), 151-159.
67. Hill T.P., Spater D., Taketo M.M., Birchmeier W. and Hartmann C. (2005). Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes. Dev. Cell. 8, 727-738.
68. Hollander A.P., Dickinson S.C., Sims T.J., Brun P., Cortivo R., Kon E., Marcacci M., Zanasi S., Borrione A., De Luca C., Pavesio A., Soranzo C. and Abatangelo G. (2006). Maturation of tissue engineered cartilage implanted in injured and osteoarthritic human knees. Tissue Eng. 12, 1787-1798.
69. Hong L., Colpan A. and Peptan I.A. (2006). Modulations of 17-beta estradiol on osteogenic and adipogenic differentiations of human mesenchymal stem cells. Tissue Eng. 12, 2747-2753.
70. Hunter D.J. (2008). Are there promising biologic therapies for osteoarthritis? Curr. Rheumatol. Rep. 10, 19-25.
71. Hunziker E.B. (2001). Growth-factor-induced healing of partial-thickness defects in adult articular cartilage. Osteoarthritis Cartilage 9, 22-32.
72. Hunziker E.B. (2002). Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. Osteoarthritis Cartilage 10, 432-463.
73. Huss R., Lange C., Weissinger E.M., Kolb H.J. and Thalmeier K. (2000). Evidence of peripheral blood-derived, plastic-adherent CD34(-/low) hematopoietic stem cell clones with mesenchymal stem cell characteristics. Stem Cells 18, 252-260.
74. Im G.I., Kim D.Y., Shin J.H., Hyun C.W. and Cho W.H. (2001). Repair of cartilage defect in the rabbit with cultured mesenchymal stem cells from bone marrow. J. Bone Joint Surg. Br. 83, 289-294.
75. Im G.I., Shin Y.W. and Lee K.B. (2005). Do adipose tissue-derived mesenchymal stem cells have the same osteogenic and chondrogenic potential as bone marrow-derived cells? Osteoarthritis Cartilage 13, 845-853.
76. Indrawattana N., Chen G., Tadokoro M., Shann L.H., Ohgushi H., Tateishi T., Tanaka J. and Bunyaratvej A. (2004). Growth factor combination for chondrogenic induction from human mesenchymal stem cell. Biochem. Biophys. Res. Commun. 320, 914-919.
77. Jaiswal R.K., Jaiswal N., Bruder S.P., Mbalaviele G., Marshak D.R. and Pittenger M.F. (2000). Adult human mesenchymal stem cell differentiation to the osteogenic or adipogenic lineage is regulated by mitogen-activated protein kinase. J. Biol. Chem. 275, 9645-9652.
78. Jakob M., Demarteau O., Schafer D., Hintermann B., Dick W., Heberer M. and Martin I. (2001). Specific growth factors during the expansion and redifferentiation of adult human articular chondrocytes enhance chondrogenesis and cartilaginous tissue formation in vitro. J. Cell. Biochem. 81, 368-377.
79. Jenniskens Y.M., Koevoet W., de Bart A.C., Weinans H., Jahr H., Verhaar J.A., DeGroot J. and van Osch G.J. (2006). Biochemical and functional modulation of the cartilage collagen network by IGF1, TGFbeta2 and FGF2. Osteoarthritis Cartilage 14, 1136-1146.
80. Jian H., Shen X., Liu I., Semenov M., He X. and Wang X.F. (2006). Smad3-dependent nuclear translocation of beta-catenin is required for TGF-beta1-induced proliferation of bone marrow-derived adult human mesenchymal stem cells. Genes Dev. 20, 666-674.
81. Johnstone B., Hering T.M., Caplan A.I., Goldberg V.M. and Yoo J.U. (1998). In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells. Exp. Cell Res. 238, 265-272.
82. Jurgensen K., Aeschlimann D., Cavin V., Genge M. and Hunziker E.B. (1997). A new biological glue for cartilage-cartilage interfaces: tissue transglutaminase. J. Bone Joint Surg. Am. 79, 185-193.
83. Kajiwara R., Ishida O., Kawasaki K., Adachi N., Yasunaga Y. and Ochi M. (2005). Effective repair of a fresh osteochondral defect in the rabbit knee joint by articulated joint distraction following subchondral drilling. J. Orthop. Res. 23, 909-915.
84. Kannus P. (2000). Structure of the tendon connective tissue. Scand. J. Med. Sci. Sports 10, 312-320.
85. Kelm J.M. and Fussenegger M. (2004). Microscale tissue engineering using gravity-enforced cell assembly. Trends Biotechnol. 22, 195-202.
86. Kern S., Eichler H., Stoeve J., Kluter H. and Bieback K. (2006). Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells 24, 1294-1301.
87. Kitagaki J., Iwamoto M., Liu J.G., Tamamura Y., Pacifci M. and Enomoto-Iwamoto M. (2003). Activation of beta-catenin-LEF/TCF signal pathway in chondrocytes stimulates ectopic endochondral ossification. Osteoarthritis Cartilage 11, 36-43.
88. Knippenberg M., Helder M.N., Zandieh Doulabi B., Wuisman P.I. and Klein-Nulend J. (2006). Osteogenesis versus chondrogenesis by BMP-2 and BMP-7 in adipose stem cells. Biochem. Biophys. Res. Commun. 342, 902-908.
89. Koch T.G., Heerkens T., Thomsen P.D. and Betts D.H. (2007). Isolation of mesenchymal stem cells from equine umbilical cord blood. BMC Biotechnol. 7, 26.
90. Koga H., Muneta T., Ju Y.J., Nagase T., Nimura A., Mochizuki T., Ichinose S., von der Mark K. and Sekiya I. (2007). Synovial stem cells are regionally specified according to local microenvironments after implantation for cartilage regeneration. Stem Cells 25, 689-696.
91. Kogler G., Sensken S., Airey J.A., Trapp T., Muschen M., Feldhahn N., Liedtke S., Sorg R.V., Fischer J., Rosenbaum C., Greschat S., Knipper A., Bender J., Degistirici O., Gao J., Caplan A.I., Colletti E.J., Almeida-Porada G., Muller H.W., Zanjani E. and Wernet P. (2004). A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential. J. Exp. Med. 200, 123-135.
92. Kramer P.R., Nares S., Kramer S.F., Grogan D. and Kaiser M. (2004). Mesenchymal stem cells acquire characteristics of cells in the periodontal ligament in vitro. J. Dent. Res. 83, 27-34.
93. Krampera M., Pizzolo G., Aprili G. and Franchini M. (2006). Mesenchymal stem cells for bone, cartilage, tendon and skeletal muscle repair. Bone 39, 678-683.
94. Lange C., Schroeder J., Stute N., Lioznov M.V. and Zander A.R. (2005). High-potential human mesenchymal stem cells. Stem Cells Dev. 14, 70-80.
95. Lee C.R., Grodzinsky A.J., Hsu H.P. and Spector M. (2003). Effects of a cultured autologous chondrocyte-seeded type II collagen scaffold on the healing of a chondral defect in a canine model. J. Orthop. Res. 21, 272-281.
96. Liu Y., Shu X.Z. and Prestwich G.D. (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.
97. Longobardi L., O'Rear L., Aakula S., Johnstone B., Shimer K., Chytil A., Horton W.A., Moses H.L. and Spagnoli A. (2006). Effect of IGF-I in the chondrogenesis of bone marrow mesenchymal stem cells in the presence or absence of TGF-beta signaling. J. Bone Miner. Res. 21, 626-636.
98. Luyten F.P., Yu Y.M., Yanagishita M., Vukicevic S., Hammonds R.G. and Reddi A.H. (1992). Natural bovine osteogenin and recombinant human bone morphogenetic protein-2B are equipotent in the maintenance of proteoglycans in bovine articular cartilage explant cultures. J. Biol. Chem. 267, 3691-3695.
99. Magne D., Vinatier C., Julien M., Weiss P. and Guicheux J. (2005). Mesenchymal stem cell therapy to rebuild cartilage. Trends Mol. Med. 11, 519-526.
100. Mainil-Varlet P., Rieser F., Grogan S., Mueller W., Saager C. and Jakob R.P. (2001). Articular cartilage repair using a tissue-engineered cartilage-like implant: an animal study. Osteoarthritis Cartilage 9 Suppl A, S6-15.
101. Majumdar M.K., Banks V., Peluso D.P. and Morris E.A. (2000). Isolation, characterization, and chondrogenic potential of human bone marrow-derived multipotential stromal cells. J. Cell Physiol. 185, 98-106.
102. Marco F., Lopez-Oliva F., Fernandez Fernandez-Arroyo J.M., de Pedro J.A., Perez A.J., Leon C. and Lopez-Duran L. (1993). Osteochondral allografts for osteochondritis dissecans and osteonecrosis of the femoral condyles. Int. Orthop. 17, 104-108.
103. Marlovits S., Hombauer M., Truppe M., Vecsei V. and Schlegel W. (2004). Changes in the ratio of type-I and type-II collagen expression during monolayer culture of human chondrocytes. J. Bone Joint Surg. Br. 86, 286-295.
104. Marlovits S., Tichy B., Truppe M., Gruber D. and Vecsei V. (2003). Chondrogenesis of aged human articular cartilage in a scaffold-free bioreactor. Tissue Eng. 9, 1215-1226.
105. Marlovits S., Zeller P., Singer P., Resinger C. and Vecsei V. (2006). Cartilage repair: generations of autologous chondrocyte transplantation. Eur. J. Radiol. 57, 24-31.
106. McAlindon T.E. (2006). Nutraceuticals: do they work and when should we use them? Best Pract. Res. Clin. Rheumatol. 20, 99-115.
107. Mehlhorn A.J. and Brown D.A. (2007). Safety concerns with fluoroquinolones. Ann. Pharmacother. 41, 1859-1866.
108. Meinel L., Hofmann S., Karageorgiou V., Zichner L., Langer R., Kaplan D. and Vunjak-Novakovic G. (2004). Engineering cartilage-like tissue using human mesenchymal stem cells and silk protein scaffolds. Biotechnol. Bioeng. 88, 379-391.
109. Mercier N.R., Costantino H.R., Tracy M.A. and Bonassar L.J. (2005). Poly(lactide-co-glycolide) microspheres as a moldable scaffold for cartilage tissue engineering. Biomaterials. 26, 1945-1952.
110. Meyers M.H., Jones R.E., Bucholz R.W. and Wenger D.R. (1983). Fresh autogenous grafts and osteochondral allografts for the treatment of segmental collapse in osteonecrosis of the hip. Clin. Orthop. Relat. Res. 174, 107-112.
111. Miao D. and Scutt A. (2002). Histochemical localization of alkaline phosphatase activity in decalcified bone and cartilage. J. Histochem. Cytochem. 50, 333-340.
112. Murakami S., Kan M., McKeehan W.L. and de Crombrugghe B. (2000). Up-regulation of the chondrogenic Sox9 gene by fibroblast growth factors is mediated by the mitogen-activated protein kinase pathway. Proc. Natl. Acad. Sci. USA 97, 1113-1118.
113. Murphy J.M., Fink D.J., Hunziker E.B. and Barry F.P. (2003). Stem cell therapy in a caprine model of osteoarthritis. Arthritis Rheum. 48, 3464-3474.
114. Nakayama N., Duryea D., Manoukian R., Chow G. and Han C.Y. (2003). Macroscopic cartilage formation with embryonic stem-cell-derived mesodermal progenitor cells. J. Cell Sci. 116, 2015-2028.
115. Naumann A., Dennis J.E., Awadallah A., Carrino D.A., Mansour J.M., Kastenbauer E. and Caplan A.I. (2002). Immunochemical and mechanical characterization of cartilage subtypes in rabbit. J. Histochem. Cytochem. 50, 1049-1058.
116. Nixon A.J., Brower-Toland B.D., Bent S.J., Saxer R.A., Wilke M.J., Robbins P.D. and Evans C.H. (2000). Insulinlike growth factor-I gene therapy applications for cartilage repair. Clin. Orthop. Relat. Res. 379 Suppl, S201-213.
117. Noel D., Djouad F. and Jorgense C. (2002). Regenerative medicine through mesenchymal stem cells for bone and cartilage repair. Curr. Opin. Investig. Drugs. 3, 1000-1004.
118. Ochi M., Uchio Y., Kawasaki K., Wakitani S. and Iwasa J. (2002). Transplantation of cartilage-like tissue made by tissue engineering in the treatment of cartilage defects of the knee. J. Bone Joint Surg. Br. 84, 571-578.
119. Oeppen J. and Vaupel J.W. (2002). Demography. Broken limits to life expectancy. Science 296, 1029-1031.
120. Otto W.R. and Rao J. (2004). Tomorrow's skeleton staff: mesenchymal stem cells and the repair of bone and cartilage. Cell Prolif. 37, 97-110.
121. Peterson L., Brittberg M., Kiviranta I., Akerlund E.L. and Lindahl A. (2002). Autologous chondrocyte transplantation. Biomechanics and long-term durability. Am. J. Sports Med. 30, 2-12.
122. Peterson L., Minas T., Brittberg M., Nilsson A., Sjogren-Jansson E. and Lindahl A. (2000). Two- to 9-year outcome after autologous chondrocyte transplantation of the knee. Clin. Orthop. Relat. Res. 374, 212-234.
123. Pittenger M.F., Mackay A.M., Beck S.C., Jaiswal R.K., Douglas R., Mosca J.D., Moorman M.A., Simonetti D.W., Craig S. and Marshak D.R. (1999). Multilineage potential of adult human mesenchymal stem cells. Science 284, 143-147.
124. Qu C.Q., Zhang G.H., Zhang L.J. and Yang G.S. (2007). Osteogenic and adipogenic potential of porcine adipose mesenchymal stem cells. In Vitro Cell Dev. Biol. Anim. 43, 95-100.
125. Quinn T.M., Grodzinsky A.J., Buschmann M.D., Kim Y.J. and Hunziker E.B. (1998a). Mechanical compression alters proteoglycan deposition and matrix deformation around individual cells in cartilage explants. J. Cell Sci. 111 (Pt 5), 573-583.
126. Quinn T.M., Grodzinsky A.J., Hunziker E.B. and Sandy J.D. (1998b). Effects of injurious compression on matrix turnover around individual cells in calf articular cartilage explants. J. Orthop. Res. 16, 490-499.
127. Quintavalla J., Uziel-Fusi S., Yin J., Boehnlein E., Pastor G., Blancuzzi V., Singh H.N., Kraus K.H., O'Byrne E. and Pellas T.C. (2002). Fluorescently labeled mesenchymal stem cells (MSCs) maintain multilineage potential and can be detected following implantation into articular cartilage defects. Biomaterials 23, 109-119.
128. Rahfoth B., Weisser J., Sternkopf F., Aigner T., von der Mark K. and Brauer R. (1998). Transplantation of allograft chondrocytes embedded in agarose gel into cartilage defects of rabbits. Osteoarthritis Cartilage 6, 50-65.
129. Richardson S.M., Mobasheri A., Freemont A.J. and Hoyland J.A. (2007). Intervertebral disc biology, degeneration and novel tissue engineering and regenerative medicine therapies. Histol. Histopathol. 22, 1033-1041.
130. Riesle J., Hollander A.P., Langer R., Freed L.E. and Vunjak-Novakovic G. (1998). Collagen in tissue-engineered cartilage: types, structure, and crosslinks. J. Cell Biochem. 71, 313-327.
131. Ringe J., Kaps C., Burmester G.R. and Sittinger M. (2002). Stem cells for regenerative medicine: advances in the engineering of tissues and organs. Naturwissenschaften 89, 338-351.
132. Roach H.I., Aigner T., Soder S., Haag J. and Welkerling H. (2007). Pathobiology of osteoarthritis: pathomechanisms and potential therapeutic targets. Curr. Drug Targets 8, 271-282.
133. Sailor L.Z., Hewick R.M. and Morris E.A. (1996). Recombinant human bone morphogenetic protein-2 maintains the articular chondrocyte phenotype in long-term culture. J. Orthop. Res. 14, 937-945.
134. Sakaguchi Y., Sekiya I., Yagishita K. and 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.
135. Schmitt B., Ringe J., Haupl T., Notter M., Manz R., Burmester G.R., Sittinger M. and Kaps C. (2003). BMP2 initiates chondrogenic lineage development of adult human mesenchymal stem cells in high-density culture. Differentiation 71, 567-577.
136. Schulze-Tanzil G., de Souza P., Villegas Castrejon H., John T., Merker H.J., Scheid A. and Shakibaei M. (2002). Redifferentiation of dedifferentiated human chondrocytes in high-density cultures. Cell Tissue Res. 308, 371-379.
137. Schulze-Tanzil G., Mobasheri A., Clegg P.D., Sendzik J., John T. and Shakibaei M. (2004a). Cultivation of human tenocytes in high-density culture. Histochem. Cell Biol. 122, 219-228.
138. Schulze-Tanzil G., Mobasheri A., de Souza P., John T. and Shakibaei M. (2004b). Loss of chondrogenic potential in dedifferentiated chondrocytes correlates with deficient Shc-Erk interaction and apoptosis. Osteoarthritis Cartilage 12, 448-458.
139. Sendzik J., Shakibaei M., Schafer-Korting M. and Stahlmann R. (2005). Fluoroquinolones cause changes in extracellular matrix, signalling proteins, metalloproteinases and caspase-3 in cultured human tendon cells. Toxicology 212, 24-36.
140. Shakibaei M. and De Souza P. (1997). Differentiation of mesenchymal limb bud cells to chondrocytes in alginate beads. Cell Biol. Int. 21, 75-86.
141. Shakibaei M. and Merker H.J. (1999). Beta1-integrins in the cartilage matrix. Cell Tissue Res. 296, 565-573.
142. Shakibaei M. and Stahlmann R. (2001). Ultrastructure of Achilles tendon from rats after treatment with fleroxacin. Arch. Toxicol. 75, 97-102.
143. Shakibaei M. and Stahlmann R. (2003). Ultrastructural changes induced by the des-F(6)-quinolone garenoxacin (BMS-284756) and two fluoroquinolones in Achilles tendon from immature rats. Arch. Toxicol. 77, 521-526.
144. Shakibaei M., Schroter-Kermani C. and Merker H.J. (1993). Matrix changes during long-term cultivation of cartilage (organoid or high-density cultures). Histol. Histopathol. 8, 463-470.
145. Shakibaei M., De Souza P. and Merker H.J. (1997). Integrin expression and collagen type II implicated in maintenance of chondrocyte shape in monolayer culture: an immunomorphological study. Cell Biol. Int. 21, 115-125.
146. Shakibaei M., Pfister K., Schwabe R., Vormann J. and Stahlmann R. (2000). Ultrastructure of Achilles tendons of rats treated with ofloxacin and fed a normal or magnesium-deficient diet. Antimicrob. Agents Chemother. 44, 261-266.
147. Shakibaei M., de Souza P., van Sickle D. and Stahlmann R. (2001a). Biochemical changes in Achilles tendon from juvenile dogs after treatment with ciprofloxacin or feeding a magnesium-deficient diet. Arch. Toxicol. 75, 369-374.
148. Shakibaei M., Schulze-Tanzil G., de Souza P., John T., Rahmanzadeh M., Rahmanzadeh R. and Merker H.J. (2001b). Inhibition of mitogen-activated protein kinase kinase induces apoptosis of human chondrocytes. J. Biol. Chem. 276, 13289-13294.
149. Shakibaei M., Seifarth C., John T., Rahmanzadeh M. and Mobasheri A. (2006). Igf-I extends the chondrogenic potential of human articular chondrocytes in vitro: molecular association between Sox9 and Erk1/2. Biochem. Pharmacol. 72, 1382-1395.
150. Shen G. (2005). The role of type X collagen in facilitating and regulating endochondral ossification of articular cartilage. Orthod. Craniofac. Res. 8, 11-17.
151. Short B., Brouard N., Occhiodoro-Scott T., Ramakrishnan A. and Simmons P.J. (2003). Mesenchymal stem cells. Arch. Med. Res. 34, 565-571.
152. Shukunami C., Oshima Y. and Hiraki Y. (2001). Molecular cloning of tenomodulin, a novel chondromodulin-I related gene. Biochem. Biophys. Res. Commun. 280, 1323-1327.
153. Sledge S.L. (2001). Microfracture techniques in the treatment of osteochondral injuries. Clin. Sports Med. 20, 365-377.
154. Solchaga L.A., Penick K., Porter J.D., Goldberg V.M., Caplan A.I. and Welter J.F. (2005a). FGF-2 enhances the mitotic and chondrogenic potentials of human adult bone marrow-derived mesenchymal stem cells. J. Cell Physiol. 203, 398-409.
155. Solchaga L.A., Temenoff J.S., Gao J., Mikos A.G., Caplan A.I. and Goldberg V.M. (2005b). Repair of osteochondral defects with hyaluronan- and polyester-based scaffolds. Osteoarthritis Cartilage 13, 297-309.
156. Solursh M. (1989). Extracellular matrix and cell surface as determinants of connective tissue differentiation. Am. J. Med. Genet. 34, 30-34.
157. Sonoyama W., Liu Y., Fang D., Yamaza T., Seo B.M., Zhang C., Liu H., Gronthos S., Wang C.Y., Shi S. and Wang S. (2006). Mesenchymal stem cell-mediated functional tooth regeneration in swine. PLoS ONE 1, e79.
158. Stegenga B., de Bont L.G., Boering G. and van Willigen J.D. (1991). Tissue responses to degenerative changes in the temporomandibular joint: a review. J. Oral Maxillofac. Surg. 49, 1079-1088.
159. Tallheden T., Brittberg M., Peterson L. and Lindahl A. (2006). Human articular chondrocytes - plasticity and differentiation potential. Cells Tissues Organs 184, 55-67.
160. Tallheden T., Karlsson C., Brunner A., Van Der Lee J., Hagg R., Tommasini R. and Lindahl A. (2004). Gene expression during redifferentiation of human articular chondrocytes. Osteoarthritis Cartilage 12, 525-535.
161. Tamamura Y., Otani T., Kanatani N., Koyama E., Kitagaki J., Komori T., Yamada Y., Costantini F., Wakisaka S., Pacifici M., Iwamoto M. and Enomoto-Iwamoto M. (2005). Developmental regulation of Wnt/beta-catenin signals is required for growth plate assembly, cartilage integrity, and endochondral ossification. J. Biol. Chem. 280, 19185-19195.
162. Till J.E. and McCulloch E.A. (1980). Hemopoietic stem cell differentiation. Biochim. Biophys. Acta 605, 431-459.
163. Trubiani O., Di Primio R., Traini T., Pizzicannella J., Scarano A., Piattelli A. and Caputi S. (2005). Morphological and cytofluorimetric analysis of adult mesenchymal stem cells expanded ex vivo from periodontal ligament. Int. J. Immunopathol. Pharmacol. 18, 213-221.
164. Trubiani O., Orsini G., Caputi S. and Piatelli A. (2006). Adult mesenchymal stem cells in dental research: a new approach for tissue engineering. Int. J. Immunopathol. Pharmacol. 19, 451-460.
165. Trumble T.N. (2005). The use of nutraceuticals for osteoarthritis in horses. Vet. Clin. North Am. Equine Pract. 21, 575-597, v-vi.
166. Tsutsumi S., Shimazu A., Miyazaki K., Pan H., Koike C., Yoshida E., Takagishi K. and Kato Y. (2001). Retention of multilineage differentiation potential of mesenchymal cells during proliferation in response to FGF. Biochem. Biophys. Res. Commun. 288, 413-419.
167. Tuli R., Li W.J. and Tuan R.S. (2003). Current state of cartilage tissue engineering. Arthritis Res. Ther. 5, 235-238.
168. Ukai R., Honmou O., Harada K., Houkin K., Hamada H. and Kocsis J.D. (2007). Mesenchymal stem cells derived from peripheral blood protects against ischemia. J. Neurotrauma. 24, 508-520.
169. Vachon A., Bramlage L.R., Gabel A.A. and Weisbrode S. (1986). Evaluation of the repair process of cartilage defects of the equine third carpal bone with and without subchondral bone perforation. Am. J. Vet Res. 47, 2637-2645.
170. von der Mark K. (1980). Immunological studies on collagen type
171. von der Mark K., Gauss V., von der Mark H. and Muller P. (1977). Relationship between cell shape and type of collagen synthesised as chondrocytes lose their cartilage phenotype in culture. Nature 267, 531-532.
172. Wakitani S., Goto T., Pineda S.J., Young R.G., Mansour J.M., Caplan A.I. and Goldberg V.M. (1994). Mesenchymal cell-based repair of large, full-thickness defects of articular cartilage. J. Bone Joint Surg. Am. 76, 579-592.
173. Wakitani S., Goto T., Young R.G., Mansour J.M., Goldberg V.M. and Caplan A.I. (1998). Repair of large full-thickness articular cartilage defects with allograft articular chondrocytes embedded in a collagen gel. Tissue Eng. 4, 429-444.
174. Wakitani S., Imoto K., Yamamoto T., Saito M., Murata N. and 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.
175. Watt S.M. and Contreras M. (2005). Stem cell medicine: umbilical cord blood and its stem cell potential. Semin. Fetal Neonatal Med. 10, 209-220.
176. Weigl M., Cieza A., Cantista P., Reinhardt J.D. and Stucki G. (2008). Determinants of disability in chronic musculoskeletal health conditions: a literature review. Eur. J. Phys. Rehabil. Med. 44, 67-79.
177. Williams J.T., Southerland S.S., Souza J., Calcutt A.F. and Cartledge R.G. (1999). Cells isolated from adult human skeletal muscle capable of differentiating into multiple mesodermal phenotypes. Am. Surg. 65, 22-26.
178. Wohl G., Goplen G., Ford J., Novak K., Hurtig M., McPherson R., McGann L., Schachar N. and Zernicke R.F. (1998). Mechanical integrity of subchondral bone in osteochondral autografts and allografts. Can. J. Surg. 41, 228-233.
179. Yamamoto N., Akamatsu H., Hasegawa S., Yamada T., Nakata S., Ohkuma M., Miyachi E., Marunouchi T. and Matsunaga K. (2007). Isolation of multipotent stem cells from mouse adipose tissue. J. Dermatol. Sci. 48, 43-52.
180. Yoo J.U., Barthel T.S., Nishimura K., Solchaga L., Caplan A.I., Goldberg V.M. and Johnstone B. (1998). The chondrogenic potential of human bone-marrow-derived mesenchymal progenitor cells. J. Bone Joint Surg. Am. 80, 1745-1757.
181. Zhang Z., McCaffery J.M., Spencer R.G. and Francomano C.A. (2004). Hyaline cartilage engineered by chondrocytes in pellet culture: histological, immunohistochemical and ultrastructural analysis in comparison with cartilage explants. J. Anat. 205, 229-237.
182. Zhou S., Eid K. and Glowacki J. (2004). Cooperation between TGF-beta and Wnt pathways during chondrocyte and adipocyte differentiation of human marrow stromal cells. J. Bone Miner. Res. 19, 463-470.
183. Zuk P.A., Zhu M., Ashjian P., De Ugarte D.A., Huang J.I., Mizuno H., Alfonso Z.C., Fraser J.K., Benhaim P. and Hedrick M.H. (2002). Human adipose tissue is a source of multipotent stem cells. Mol. Biol. Cell 13, 4279-4295.
184. Zuk P.A., Zhu M., Mizuno H., Huang J., Futrell J.W., Katz A.J., Benhaim P., Lorenz H.P. and Hedrick M.H. (2001). Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 7, 211-228.
185. Zvaifler N.J., Marinova-Mutafchieva L., Adams G., Edwards C.J., Moss J., Burger J.A. and Maini R.N. (2000). Mesenchymal precursor cells in the blood of normal individuals. Arthritis Res. 2, 477-488.