Gene therapy for cartilage defects

Journal of Gene Medicine

Volumn 7, Issue 12, 2005, Pages 1495-1509

  Cucchiarini, Magali ^a   Madry, Henning ^a  

^a SAARLAND UNIVERSITY   (Germany)

Author keywords

Cartilage defects; Chondrocytes; Gene therapy; Transplantation vectors

Indexed keywords

ADENOVIRUS VECTOR; BONE MORPHOGENETIC PROTEIN 13; BONE MORPHOGENETIC PROTEIN 2; CARTILAGE OLIGOMERIC MATRIX PROTEIN; COLLAGEN TYPE 14; COLLAGEN TYPE 2; COLLAGEN TYPE 6; COLLAGEN TYPE 9; DECORIN; FIBROBLAST GROWTH FACTOR 2; FIBRONECTIN; GROWTH DIFFERENTIATION FACTOR 5; GROWTH FACTOR; LENTIVIRUS VECTOR; LINK PROTEIN; LIPOFECTAMINE; LIPOFECTIN; OSTEOGENIC PROTEIN 1; PARATHYROID HORMONE RELATED PROTEIN; RECOMBINANT BONE MORPHOGENETIC PROTEIN 2; RETROVIRUS VECTOR; SOMATOMEDIN C; SONIC HEDGEHOG PROTEIN; TENASCIN; TRANSCRIPTION FACTOR ETS; TRANSCRIPTION FACTOR RUNX2; TRANSCRIPTION FACTOR SOX9; TRANSFORMING GROWTH FACTOR BETA1; TRANSFORMING GROWTH FACTOR BETA2; TUMOR NECROSIS FACTOR ALPHA; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR 4; UNCLASSIFIED DRUG; UNINDEXED DRUG; WNT PROTEIN;

ARTHRITIS; ARTHROPLASTY; ARTICULAR CARTILAGE; CARTILAGE CELL; CARTILAGE TRANSPLANTATION; CELL MATURATION; CELL PROLIFERATION; CELL TRANSPLANTATION; CHONDROGENESIS; CHONDROPATHY; CONSERVATIVE TREATMENT; DRUG CLEARANCE; DRUG EFFICACY; DRUG HALF LIFE; DRUG TARGETING; GENE EXPRESSION; GENE THERAPY; GENE TRANSFER; GENETIC TRANSDUCTION; HUMAN; JOINT SURGERY; MOVEMENT THERAPY; NONHUMAN; NONVIRAL GENE DELIVERY SYSTEM; NONVIRAL GENE THERAPY; PRIORITY JOURNAL; REVIEW; STEM CELL; TISSUE REGENERATION; TISSUE REPAIR; VIRAL GENE DELIVERY SYSTEM; VIRAL GENE THERAPY;

CARTILAGE, ARTICULAR; CELL TRANSPLANTATION; CHONDROGENESIS; GENE THERAPY; GENE TRANSFER TECHNIQUES; GENETIC VECTORS; GROWTH SUBSTANCES; HUMANS; ORTHOPEDICS;

ADENOVIRIDAE; ERINACEIDAE; LENTIVIRUS;

EID: 29744465669     PISSN: 1099498X     EISSN: 15212254     Source Type: Journal    
DOI: 10.1002/jgm.824     Document Type: Review

References (176)

1. Evans CH, Robbins PD, Ghivizzani SC, et al. Clinical trial to assess the safety, feasibility, and efficacy of transferring a potentially anti-arthritic cytokine gene to human joints with rheumatoid arthritis. Hum Gene Ther 1996; 7: 1261-1280.
2. Evans CH, Ghivizzani SC, Smith P, et al. Using gene therapy to protect and restore cartilage. Clin Orthop 2000; 379: S214-219.
3. Huard J, Li Y, Peng H, et al. Gene therapy and tissue engineering for sports medicine. J Gene Med 2003; 5: 91-108.
4. Martinek V, Ueblacker P, Imhoff AB. Current concepts of gene therapy and cartilage repair. J Bone Joint Surg Br 2003; 85: 782-788.
5. Evans CH, Gouze JN, Gouze E, et al. Osteoarthritis gene therapy. Gene Ther 2004; 11: 379-389.
6. Trippel SB, Ghivizzani SC, Nixon AJ. Gene-based approaches for the repair of articular cartilage. Gene Ther 2004; 11: 351-359.
7. Hunziker EB, Michel M, Studer D. Ultrastructure of adult human articular cartilage matrix after cryotechnical processing. Microsc Res Technol 1997; 37: 271-284.
8. O'Driscoll SW. The healing and regeneration of articular cartilage. J Bone Joiznt Surg Am 1998; 80: 1795-1812.
9. Noyes FR, Stabler CL. A system for grading articular cartilage lesions at arthroscopy. Am J Sports Med 1989; 17: 505-513.
10. Hunziker EB, Rosenberg LC. Repair of partial-thickness defects in articular cartilage: cell recruitment from the synovial membrane. J Bone Joint Surg Am 1996; 78: 721-733.
11. Hunziker EB. Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. Osteoarthritis Cartilage 2002; 10: 432-463.
12. Furukawa T, Eyre DR, Koide S, et al. Biochemical studies on repair cartilage resurfacing experimental defects in the rabbit knee. J Bone Joint Surg Am 1980; 62: 79-89.
13. Shapiro F, Koide S, Glimcher MJ. Cell origin and differentiation in the repair of full-thickness defects of articular cartilage. J Bone Joint Surg Am 1993; 75: 532-553.
14. Jackson DW, Lalor PA, Aberman HM, et al. Spontaneous repair of full-thickness defects of articular cartilage in a goat model. A preliminary study. J Bone Joint Surg Am 2001; 83-A: 53-64.
15. Salter RB. The biologic concept of continuous passive motion of synovial joints. The first 18 years of basic research and its clinical application. Clin Orthop 1989; 242: 12-25.
16. O'Driscoll SW, Salter RB. The induction of neochondrogenesis in free intra-articular periosteal autografts under the influence of continuous passive motion. An experimental investigation in the rabbit. J Bone Joint Surg Am 1984; 66: 1248-1257.
17. Czitrom AA, Langer F, McKee N, et al. Bone and cartilage allotransplantation. A review of 14 years of research and clinical studies. Clin Orthop 1986; 208: 141-145.
18. Brittberg M, Lindahl A, Nilsson A, et al. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med 1994; 331: 889-895.
19. Ochi M, Uchio Y, Kawasaki K, et al. Transplantation of cartilage-like tissue made by tissue engineering in the treatment of cartilage defects of the knee. J Bone Joint Surg Br 2002; 84: 571-578.
20. Buckwalter JA, Markin HJ. Articular cartilage: degeneration and osteoarthritis, repair, regeneration, and transplantation. Instr Course Lect 1998; 47: 487-504.
21. Knutsen G, Engebretsen L, Ludvigsen TC, et al. Autologous chondrocyte implantation compared with microfracture in the knee. A randomized trial. J Bone Joint Surg Am 2004; 86-A: 455-464.
22. Tibesku CO, Szuwart T, Kleffner TO, et al. Hyaline cartilage degenerates after autologous osteochondral transplantation. J Orthop Res 2004; 22: 1210-1214.
23. Gies T. Ueber Heilung von Knorpelwunden. Deutsche Zeitschrift für Chirurgie 1883; 18: 8-34.
24. Seggel R. Experimentelle Beiträge zur Anatomic und Pathologie des Gelenkknorpels. Studien über Knorpelwunden und Defekte. Deutsche Zeitschrift für Chirurgie 1904; 21: 453-466.
25. Trippel SB. Growth factors as therapeutic agents. Instr Course Lect 1997; 46: 473-476.
26. Lo YY, Cruz TF. Involvement of reactive oxygen species in cytokine and growth factor induction of c-fos expression in chondrocytes. J Biol Chem 1995; 270: 11727-11730.
27. Fortier LA, Deak MM, Semevolos SA, et al. Insulin-like growth factor-I diminishes the activation status and expression of the small GTPase Cdc42 in articular chondrocytes. J Orthop Res 2004; 22: 436-445.
28. Rogachefsky RA, Dean DD, Howell DS, et al. Treatment of canine osteoarthritis with insulin-like growth factor-1 (IGF-1) and sodium pentosan polysulfate. Osteoarthritis Cartilage 1993; 1: 105-114.
29. Shida J, Jingushi S, Izumi T, et al. Basic fibroblast growth factor stimulates articular cartilage enlargement in young rats in vivo. J Orthop Res 1996; 14: 265-272.
30. Sellers RS, Peluso D, Morris EA. The effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) on the healing of full-thickness defects of articular cartilage. J Bone Joint Surg Am 1997; 79: 1452-1463.
31. Chuma H, Mizuta H, Kudo S, et al. One day exposure to FGF-2 was sufficient for the regenerative repair of full-thickness defects of articular cartilage in rabbits. Osteoarthritis Cartilage 2004; 12: 834-842.
32. Joyce ME, Roberts AB, Sporn MB, et al. Transforming growth factor-beta and the initiation of chondrogenesis and osteogenesis in the rat femur. J Cell Biol 1990; 110: 2195-2207.
33. Hanada K, Solchaga LA, Caplan AI, et al. BMP-2 induction and TGF-beta 1 modulation of rat periosteal cell chondrogenesis. J Cell Biochem 2001; 81: 284-294.
34. Asahina I, Sampath TK, Hauschka PV. Human osteogenic protein-1 induces chondroblastic, osteoblastic, and/or adipocytic differentiation of clonal murine target cells. Exp Cell Res 1996; 222: 38-47.
35. Klein-Nulend J, Louwerse RT, Heyligers IC, et al. Osteogenic protein (OP-1, BMP-7) stimulates cartilage differentiation of human and goat perichondrium tissue in vitro. J Biomed Mater Res 1998; 40: 614-620.
36. Gospodarowicz D. Localisation of a fibroblast growth factor and its effect alone and with hydrocortisone on 3T3 cell growth. Nature 1974; 249: 123-127.
37. Jentzsch KD, Wellmitz G, Heder G, et al. A bovine brain fraction with fibroblast growth factor activity inducing articular cartilage regeneration in vivo. Acta Biol Med Ger 1980; 39: 967-971.
38. Hotten GC, Matsumoto T, Kimura M, et al. Recombinant human growth/differentiation factor 5 stimulates mesenchyme aggregation and chondrogenesis responsible for the skeletal development of limbs. Growth Factors 1996; 13: 65-74.
39. Amizuka N, Warshawsky H, Henderson JE, et al. Parathyroid hormone-related peptide-depleted mice show abnormal epiphyseal cartilage development and altered endochondral bone formation. J Cell Biol 1994; 126: 1611-1623.
40. Vortkamp A, Lee K, Lanske B, et al. Regulation of rate of cartilage differentiation by Indian hedgehog and PTH-related protein. Science 1996; 273: 613-622.
41. Trippel SB, Wroblewski J, Makower AM, et al. Regulation of growth-plate chondrocytes by insulin-like growth-factor I and basic fibroblast growth factor. J Bone Joint Surg Am 1993; 75: 177-189.
42. Fujimoto E, Ochi M, Kato Y, et al. Beneficial effect of basic fibroblast growth factor on the repair of full-thickness defects in rabbit articular cartilage. Arch Orthop Trauma Surg 1999; 119: 139-145.
43. Trippel SB. Growth factor actions on articular cartilage. J Rheumatol Suppl 1995; 43: 129-132.
44. Nixon AJ, Fortier LA, Williams J, et al. Enhanced repair of extensive articular defects by insulin-like growth factor-I-laden fibrin composites. J Orthop Res 1999; 17: 475-487.
45. Trippel SB, Van Wyk JJ, Foster MB, et al. Characterization of a specific somatomedin-c receptor on isolated bovine growth plate chondrocytes. Endocrinology 1983; 112: 2128-2136.
46. Erlacher L, Ng CK, Ullrich R, et al. Presence of cartilage-derived morphogenetic proteins in articular cartilage and enhancement of matrix replacement in vitro. Arthritis Rheum 1998; 41: 263-273.
47. Bi W, Deng JM, Zhang Z, et al. Sox9 is required for cartilage formation. Nat Genet 1999; 22: 85-89.
48. Inada M, Yasui T, Nomura S, et al. Maturational disturbance of chondrocytes in Cbfa1-deficient mice. Dev Dyn 1999; 214: 279-290.
49. Zhao GQ, Eberspaecher H, Seldin MF, et al. The gene for the homeodomain-containing protein Cart-1 is expressed in cells that have a chondrogenic potential during embryonic development. Mech Dev 1994; 48: 245-254.
50. Sumarsono SH, Wilson TJ, Tymms MJ, et al. Down's syndrome-like skeletal abnormalities in Ets2 transgenic mice. Nature 1996; 379: 534-537.
51. Hartmann C, Tabin CJ. Dual roles of Wnt signaling during chondrogenesis in the chicken limb. Development 2000; 127: 3141-3159.
52. Lanske B, Karaplis AC, Lee K, et al. PTH/PTHrP receptor in early development and Indian hedgehog-regulated bone growth. Science 1996; 273: 663-666.
53. Mackie EJ, Thesleff I, Chiquet-Ehrismann R. Tenascin is associated with chondrogenic and osteogenic differentiation in vivo and promotes chondrogenesis in vitro. J Cell Biol 1987; 105: 2569-2579.
54. Moser M, Bosserhoff AK, Hunziker EB, et al. Ultrastructural cartilage abnormalities in MIA/CD-RAP-deficient mice. Mol Cell Biol 2002; 22: 1438-1445.
55. Goldring MB, Fukuo K, Birkhead JR, et al. Transcriptional suppression by interleukin-1 and interferon-gamma of type II collagen gene expression in human chondrocytes. J Cell Biochem 1994; 54: 85-99.
56. Stadler J, Stefanovie-Racic M, Billiar TR, et al. Articular chondrocytes synthesize nitric oxide in response to cytokines and lipopolysaccharide. J Immunol 1991; 147: 3915-3920.
57. Shalom-Barak T, Quach J, Lotz M. Interleukin-17-induced gene expression in articular chondrocytes is associated with activation of mitogen-activated protein kinases and NF-kappaB. J Biol Chem 1998; 273: 27467-27473.
58. Pelletier JP, DiBattista JA, Roughley P, et al. Cytokines and inflammation in cartilage degradation. Rheum Dis Clin North Am 1993; 19: 545-568.
59. Blanco FJ, Ochs RL, Schwarz H, et al. Chondrocyte apoptosis induced by nitric oxide. Am J Pathol 1995; 146: 75-85.
60. Johnstone B, Hering TM, Caplan AI, et al. In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells. Exp Cell Res 1998; 238: 265-272.
61. Pereira RF, Halford KW, O'Hara MD, et al. Cultured adherent cells from marrow can serve as long-lasting precursor cells for bone, cartilage, and lung in irradiated mice. Proc Natl Acad Sci USA 1995; 92: 4857-4861.
62. Peng H, Huard J. Muscle-derived stem cells for musculoskeletal tissue regeneration and repair. Transpl Immunol 2004; 12: 311-319.
63. Nishimura K, Solchaga LA, Caplan AI, et al. Chondroprogenitor cells of synovial tissue. Arthritis Rheum 1999; 42: 2631-2637.
64. Mason JM, Grande DA, Barcia M, et al. Expression of human bone morphogenic protein 7 in primary rabbit periosteal cells: potential utility in gene therapy for osteochondral repair. Gene Ther 1998; 5: 1098-1104.
65. Grande DA, Mason J, Light E, Dines D. Stem cells as platforms for delivery of genes to enhance cartilage repair. J Bone Joint Surg Am 2003; 85-A(Suppl 2): 111-116.
66. Gelse K, von der Mark K, Aigner T, et al. Articular cartilage repair by gene therapy using growth factor-producing mesenchymal cells. Arthritis Rheum 2003; 48: 430-441.
67. Day CS, Kasemkijwattana C, Menetrey J, et al. Myoblast-mediated gene transfer to the joint. J Orthop Res 1997; 15: 894-903.
68. Adachi N, Sato K, Usas A, et al. Muscle derived, cell based ex vivo gene therapy for treatment of full thickness articular cartilage defects. J Rheumatol 2002; 29: 1920-1930.
69. Nixon AJ, Brower-Toland BD, Bent SJ, et al. Insulinlike growth factor-I gene therapy applications for cartilage repair. Clin Orthop 2000; 43: S201-213.
70. Turgeman G, Pittman DD, Muller R, et al. Engineered human mesenchymal stem cells: a novel platform for skeletal cell mediated gene therapy. J Gene Med 2001; 3: 240-251.
71. Mosca JD, Hendricks JK, Buyaner D, et al. Mesenchymal stem cells as vehicles for gene delivery. Clin Orthop 2000; 379: S71-90.
72. Allay JA, Dennis JE, Haynesworth SE, et al. LacZ and interleukin-3 expression in vivo after retroviral transduction of marrow-derived human osteogenic mesenchymal progenitors. Hum Gene Ther 1997; 8: 1417-1427.
73. Milbrandt T, Berthoux L, Christenson V, et al. Tracing transduced cells in osteochondral defects. J Pediatr Orthop 2003; 23: 430-436.
74. Madry H, Cucchiarini M, Terwilliger EF, et al. Efficient and persistent gene transfer into articular cartilage using recombinant adeno-associated virus vectors in vitro and in vivo. Hum Gene Ther 2003; 14: 393-402.
75. Ito H, Goater JJ, Tiyapatanaputi P, et al. Light-activated gene transduction of recombinant adeno-associated virus in human mesenchymal stem cells. Gene Ther 2004; 11: 34-41.
76. Cucchiarini M, Madry H, Ma C, et al. Improved tissue repair in articular cartilage defects in vivo by rAAV-mediated overexpression of human fibroblast growth factor 2. Mol Ther 2005; 12: 229-238.
77. Katayama R, Wakitani S, Tsumaki N, et al. Repair of articular cartilage defects in rabbits using CDMP1 gene-transfected autologous mesenchymal cells derived from bone marrow. Rheumatology (Oxford) 2004; 43: 980-985.
78. Hoelters J, Ciccarella M, Drechsel M, et al. Nonviral genetic modification mediates effective transgene expression and functional RNA interference in human mesenchymal stem cells. J Gene Med 2005; 7: 718-728.
79. Rosen V, Nove J, Song JJ, et al. Responsiveness of clonal limb bud cell lines to bone morphogenetic protein 2 reveals a sequential relationship between cartilage and bone cell phenotypes. J Bone Miner Res 1994; 9: 1759-1768.
80. Carlberg AL, Pucci B, Rallapalli R, et al. Efficient chondrogenic differentiation of mesenchymal cells in micromass culture by retroviral gene transfer of BMP-2. Differentiation 2001; 67: 128-138.
81. Duprez DM, Coltey M, Amthor H, et al. Bone morphogenetic protein-2 (BMP-2) inhibits muscle development and promotes cartilage formation in chick limb bud cultures. Dev Biol 1996; 174: 448-452.
82. Nochi H, Sung JH, Lou J, et al. Adenovirus mediated BMP-13 gene transfer induces chondrogenic differentiation of murine mesenchymal progenitor cells. J Bone Miner Res 2004; 19: 111-122.
83. Mandell I, Yoo JU, Johnstone B. Gene delivery to mesenchymal cells. Trans Orthop Res Soc 1999; 24: 112.
84. Tsuchiya H, Kitoh H, Sugiura F, et al. Chondrogenesis enhanced by overexpression of sox9 gene in mouse bone marrow-derived mesenchymal stem cells. Biochem Biophys Res Commun 2003; 301: 338-343.
85. Ikeda T, Kamekura S, Mabuchi A, et al. The combination of SOX5, SOX6, and SOX9 (die SOX trio) provides signals sufficient for induction of permanent cartilage. Arthritis Rheum 2004; 50: 3561-3573.
86. Hoffmann A, Czichos S, Kaps C, et al. The T-box transcription factor Brachyury mediates cartilage development in mesenchymal stem cell line C3H10T1/2. J Cell Sci 2002; 115: 769-781.
87. Niyibizi C, Smith P, Mi Z, et al. Transfer of proalpha2(I) cDNA into cells of a murine model of human Osteogenesis Imperfecta restores synthesis of type I collagen comprised of alphal(I) and alpha2(I) heterotrimers in vitro and in vivo. J Cell Biochem 2001; 83: 84-91.
88. Okayama M, Yoshimura M, Muto M, et al. Transformation of chicken chondrocytes by Rous sarcoma virus. Cancer Res 1977; 37: 712-717.
89. Muto M, Yoshimura M, Okayama M, et al. Cellular transformation and differentiation. Effect of Rous sarcoma virus transformation on sulfated proteoglycan synthesis by chicken chondrocytes. Proc Natl Acad Sci U S A 1977; 74: 4173-4177.
90. Baragi VM, Renkiewicz RR, Jordan H, et al. Transplantation of transduced chondrocytes protects articular cartilage from interleukin 1-induced extracellular matrix degradation. J Clin Invest 1995; 96: 2454-2460.
91. Arai Y, Kubo T, Kobayashi K, et al. Adenovirus vector-mediated gene transduction to chondrocytes: in vitro evaluation of therapeutic efficacy of transforming growth factor-beta 1 and heat shock protein 70 gene transduction. J Rheumatol 1997; 24: 1787-1795.
92. Baragi VM, Renkiewicz RR, Qiu L, et al. Transplantation of adenovirally transduced allogeneic chondrocytes into articular cartilage defects in vivo. Osteoarthritis Cartilage 1997; 5: 275-282.
93. Kang R, Marui T, Ghivizzani SC, et al. Ex vivo gene transfer to chondrocytes in full-thickness articular cartilage defects: a feasibility study. Osteoarthritis Cartilage 1997; 5: 139-143.
94. Hirschmann F, Verhoeyen E, Wirth D. et al. Vital marking of articular chondrocytes by retroviral infection using green fluorescence protein. Osteoarthritis Cartilage 2002; 10: 109-118.
95. Benya PD, Padilla SR, Nimni ME. Independent regulation of collagen types by chondrocytes during the loss of differentiated function in culture. Cell 1978; 15: 1313-1321.
96. Hofmann C, Sandig V, Jennings G, et al. Efficient gene transfer into human hepatocytes by baculovirus vectors. Proc Natl Acad Sci U S A 1995; 92: 10 099-10 103.
97. Ho YC, Chen HC, Wang KC, et al. Highly efficient baculovirus-mediated gene transfer into rat chondrocytes. Biotechnol Bioeng 2004; 88: 643-651.
98. Li Y, Tew SR, Russell AM, et al. Transduction of passaged human articular chondrocytes with adenoviral, retroviral, and lentiviral vectors and the effects of enhanced expression of SOX9. Tissue Eng 2004; 10: 575-584.
99. Arai Y, Kubo T, Fushiki S, et al. Gene delivery to human chondrocytes by an adeno associated virus vector. J Rheumatol 2000; 27: 979-982.
100. Ulrich-Vinther M, Maloney MD, Goater JJ, et al. Light-activated gene transduction enhances adeno-associated virus vector-mediated gene expression in human articular chondrocytes. Arthritis Rheum 2002; 46: 2095-2104.
101. Long F. Linsenmayer TF. Tissue-specific regulation of the type X collagen gene. Analyses by in vivo footprinting and transfection with a proximal promoter region. J Biol Chem 1995; 270: 31310-31314.
102. Goldring MB, Birkhead JR, Suen LF, et al. Interleukin-1 beta-modulated gene expression in immortalized human chondrocytes. J Clin Invest 1994; 94: 2307-2316.
103. Pallante RM, Niu Z, Zhao Y, et al. The chick alpha2(I) collagen gene contains two functional promoters, and its expression in chondrocytes is regulated at both transcriptional and post-transcriptional levels. J Biol Chem 1996; 271: 25 233-25 239.
104. Lu Valle P, Iwamoto M, Fanning P, et al. Multiple negative elements in a gene that codes for an extracellular matrix protein, collagen X, restrict expression to hypertrophic chondrocytes. J Cell Biol 1993; 121: 1173-1179.
105. Dharmavaram RM, Liu G, Tuan RS, et al. Stable transfection of human fetal chondrocytes with a type II procollagen minigene: expression of the mutant protein and alterations in the structure of the extracellular matrix in vitro. Arthritis Rheum 1999; 42: 1433-1442.
106. Kim HJ, Greenleaf JF, Kinnick RR, et al. Ultrasound-mediated transfection of mammalian cells. Hum Gene Ther 1996; 7: 1339-1346.
107. Viengchareun S, Thenet-Gauci S, Steimberg N, et al. The transfection of rabbit articular chondrocytes is independent of their differentiation state. In Vitro Cell Dev Biol Anim 1997; 33: 15-17.
108. Beier F, Vornehm S, Poschl E, et al. Localization of silencer and enhancer elements in the human type X collagen gene. J Cell Biochem 1997; 66: 210-218.
109. Madry H, Trippel SB. Efficient lipid-mediated gene transfer to articular chondrocytes. Gene Ther 2000; 7: 286-291.
110. Smith P, Shuler FD, Georgescu HI, et al. Genetic enhancement of matrix synthesis by articular chondrocytes: comparison of different growth factor genes in the presence and absence of interleukin-1. Arthritis Rheum 2000; 43: 1156-1164.
111. Brower-Toland BD, Saxer RA, Goodrich LR, et al. Direct adenovirus-mediated insulin-like growth factor I gene transfer enhances transplant chondrocyte function. Hum Gene Ther 2001; 12: 117-129.
112. Shuler FD, Georgescu HI, Niyibizi C, et al. Increased matrix synthesis following adenoviral transfer of a transforming growth factor beta1 gene into articular chondrocytes. J Orthop Res 2000; 18: 585-592.
113. Moller HD, Fu FH, Niyibizi C, et al. TGFβ-1-Gentransfer in Gelenkknorpelzellen. Stimulierende Wirkung in der extrazellulären Matrixsynthese. Orthopäde 2000; 29: 75-79.
114. Dinser R, Kreppel F, Zaucke F, et al. Comparison of long-term transgene expression after non-viral and adenoviral gene transfer into primary articular chondrocytes. Histochem Cell Biol 2001; 116: 69-77.
115. Stove J, Fiedler J, Huch K, et al. Lipofection of rabbit chondrocytes and long lasting expression of a lacZ reporter system in alginate beads. Osteoarthritis Cartilage 2002; 10: 212-217.
116. Madry H, Padera B, Seidel J, et al. Gene transfer of a human insulin-like growth factor I cDNA enhances tissue engineering of cartilage. Hum Gene Ther 2002; 13: 1621-1630.
117. Madry H, Cucchiarini M, Stein U, et al. Sustained transgene expression in cartilage defects in vivo after transplantation of articular chondrocytes modified by lipid-mediated gene transfer in a gel suspension delivery system. J Gene Med 2003; 5: 502-509.
118. von der Mark K, Gauss V, von der Mark H, et al. Relationship between cell shape and type of collagen synthesis as chondrocytes lose their cartilage phenotype in culture. Nature 1977; 267: 531-532.
119. Doherty PJ, Zhang H, Tremblay L, et al. Resurfacing of articular cartilage explants with genetically-modified human chondrocytes in vitro. Osteoarthritis Cartilage 1998; 6: 153-159.
120. Madry H, Zurakowski D, Trippel SB. Overexpression of human insulin-like growth factor-I promotes new tissue formation in an ex vivo model of articular chondrocyte transplantation. Gene Ther 2001; 8: 1443-1449.
121. Hidaka C, Quitoriano M, Warren RF, et al. Enhanced matrix synthesis and in vitro formation of cartilage-like tissue by genetically modified chondrocytes expressing BMP-7. J Orthop Res 2001; 19: 751-758.
122. Madry H, Emkey G, Zurakowski D, et al. Overexpression of human fibroblast growth factor 2 stimulates cell proliferation in an ex vivo model of articular chondrocyte transplantation. J Gene Med 2004; 6: 238-245.
123. Diduch DR, Jordan LC, Mierisch CM, et al. Marrow stromal cells embedded in alginate for repair of osteochondral defects. Arthroscopy 2000; 16: 571-577.
124. Madry H, Kaul G, Cucchiarini M, et al. Enhanced repair of articular cartilage defects in vivo by transplanted chondrocytes overexpressing insulin-like growth factor I (IGF-I). Gene Ther 2005; 12: 1171-1179.
125. Kaul G, Cucchiarini M, Arntzen D, et al. Local stimulation of articular cartilage repair by transplantation of encapsulated chondrocytes overexpressing human fibroblast growth factor 2 (FGF-2) in vivo. J Gene Med 2005; in press.
126. Madry H, Thum T, Terwilliger EF, et al. rAAV-mediated overexpression of human sox9 in normal human and osteoarthritic articular cartilage explants stimulates the synthesis of type-II collagen and extracellular matrix in situ (abstract). Trans Orthop Res Soc 2005; 51: 942.
127. Tew SR, Li Y, Pothacharoen P, et al. Retroviral transduction with SOX9 enhances re-expression of the chondrocyte phenotype in passaged osteoarthritic human articular chondrocytes. Osteoarthritis Cartilage 2005; 13: 80-89.
128. Enomoto-Iwamoto M, Enomoto H, Komori T, et al. Participation of Cbfa1 in regulation of chondrocyte maturation. Osteoarthritis Cartilage 2001; 9(Suppl A): S76-84.
129. Iwamoto M, Kitagaki J, Tamamura Y, et al. Runx2 expression and action in chondrocytes are regulated by retinoid signaling and parathyroid hormone-related peptide (PTHrP). Osteoarthritis Cartilage 2003; 11: 6-15.
130. Bandara G, Mueller GM, Galea-Lauri J. Intraarticular expression of biologically active interleukin 1-receptor- antagonist protein by ex vivo gene transfer. Proc Natl Acad Sci U S A 1993; 90: 10 764-10 768.
131. Nita I, Ghivizzani SC, Galea-Lauri J, et al. Direct gene delivery to synovium. An evaluation of potential vectors in vitro and in vivo. Arthritis Rheum 1996; 39: 820-828.
132. Muller-Ladner U, Roberts CR, Franklin BN, et al. Human IL-1Ra gene transfer into human synovial fibroblasts is chondroprotective. J Immunol 1997; 158: 3492-3498.
133. Muller-Ladner U, Evans CH, Franklin BN, et al. Gene transfer of cytokine inhibitors into human spovial fibroblasts in the SCID mouse model. Arthritis Rheum 1999; 42: 490-497.
134. Pap T, Gay RE, Muller-Ladner U, et al. Ex vivo gene transfer in the years to come. Arthritis Res 2002; 4: 10-12.
135. Robbins PD, Evans CH, Chernajovsky Y. Gene therapy for arthritis. Gene Ther 2003; 10: 902-911.
136. Makarov SS, Olsen JC, Johnston WN, et al. Suppression of experimental arthritis by gene transfer of interleukin 1 receptor antagonist cDNA. Proc Natl Acad Sci U S A 1996; 93: 402-406.
137. Pelletier JP, Caron JP, Evans C, et al. In vivo suppression of early experimental osteoarthritis by interleukin-1 receptor antagonist using gene therapy. Arthritis Rheum 1997; 40: 1012-1019.
138. Gouze E, Pawliuk R, Pilapil C, et al. In vivo gene delivery to synovium by lentiviral vectors. Mol Ther 2002; 5: 397-404.
139. Roessler BJ, Allen ED, Wilson JM, et al. Adenoviral-mediated gene transfer to rabbit synovium in vivo. J Clin Invest 1993; 92: 1085-1092.
140. Ikeda T, Kubo T, Arai Y, et al. Adenovirus mediated gene delivery to the joints of guinea pigs. J Rheumatol 1998; 25: 1666-1673.
141. Ghivizzani SC, Lechman ER, Tio C, et al. Direct retrovirus-mediated gene transfer to the synovium of the rabbit knee: implications for arthritis gene therapy. Gene Ther 1997; 4: 977-982.
142. Pan RY, Xiao X, Chen SL, et al. Disease-inducible transgene expression from a recombinant adeno-associated virus vector in a rat arthritis model. J Virol 1999; 73: 3410-3417.
143. Goater J, Muller R, Kollias G, et al. Empirical advantages of adeno-associated viral vectors in vivo gene therapy for arthritis. J Rheumatol 2000; 27: 983-989.
144. Watanabe S, Kim KN, Imagawa T, et al. On the mechanism of protection of distal joints after local gene transfer in collagen-induced arthritis. Hum Gene Ther 2000; 11: 751-758.
145. Zhang HG, Xie J, Yang P, et al. Adeno-associated virus production of soluble tumor necrosis factor receptor neutralizes tumor necrosis factor alpha and reduces arthritis. Hum Gene Ther 2000; 11: 2431-2442.
146. Tomita T, Hashimoto H, Tomita N, et al. In vivo direct gene transfer into articular cartilage by intraarticular injection mediated by HVJ (Sendai virus) and liposomes. Arthritis Rheum 1997; 40: 901-906.
147. Lee KH, Song SU, Hwang TS, et al. Regeneration of hyaline cartilage by cell-mediated gene therapy using transforming growth factor beta 1-producing fibroblasts. Hum Gene Ther 2001; 12: 1805-1813.
148. Ulrich-Vinther M, Duch MR, Soballe K, et al. In vivo gene delivery to articular chondrocytes mediated by an adeno-associated virus vector. J Orthop Res 2004; 22: 726-734.
149. Pan RY, Chen SL, Xiao X, et al. Therapy and prevention of arthritis by recombinant adeno-associated virus vector with delivery of interleukin-1 receptor antagonist. Arthritis Rheum 2000; 43: 289-297.
150. Gelse K, Jiang QJ, Aigner T, et al. Fibroblast-mediated delivery of growth factor complementary DNA into mouse joints induces chondrogenesis but avoids the disadvantages of direct viral gene transfer. Arthritis Rheum 2001; 44: 1943-1953.
151. Mi Z, Ghivizzani SC, Lechinan E, et al. Adverse effects of adenovirus-mediated gene transfer of human transforming growth factor beta 1 into rabbit knees. Arthritis Res Ther 2003; 5: R132-139.
152. Mi Z, Ghivizzani SC, Lechman ER, et al. Adenovirus-mediated gene transfer of insulin-like growth factor 1 stimulates proteoglycan synthesis in rabbit joints. Arthritis Rheum 2000; 43: 2563-2570.
153. Fragonas E, Valente M, Pozzi-Mucelli M, et al. Articular cartilage repair in rabbits by using suspensions of allogenic chondrocytes in alginate. Biomaterials 2000; 21: 795-801.
154. Rahfoth B, Weisser J, Sternkopf F, et al. Transplantation of allograft chondrocytes embedded in agarose gel into cartilage defects of rabbits. Osteoarthritis Cartilage 1998; 6: 50-65.
155. Hunter CJ, Levenston ME. Maturation and integration of tissue-engineered cartilages within an in vitro defect repair model. Tissue Eng 2004; 10: 736-746.
156. Kawamura S, Wakitani S, Kimura T, et al. Articular cartilage repair. Rabbit experiments with a collagen gel biomatrix and chondrocytes cultured in it. Acta Orthop Scand 1998; 69: 56-62.
157. Ikeda T, Kubo T, Nakanishi T, et al. Ex vivo gene delivery using an adenovirus vector in treatment for cartilage defects. J Rheumatol 2000; 27: 990-996.
158. Perka C, Schultz O, Spitzer RS, et al. The influence of transforming growth factor beta1 on mesenchymal cell repair of full-thickness cartilage defects. J Biomed Mater Res 2000; 52: 543-552.
159. Driesang IM, Hunziker EB. Delamination rates of tissue flaps used in articular cartilage repair. J Orthop Res 2000; 18: 909-911.
160. Yokoo N, Saito T, Uesugi M, et al. Repair of articular cartilage defect by autologous transplantation of basic fibroblast growth factor gene-transduced chondrocytes with adeno-associated virus vector. Arthritis Rheum 2005; 52: 164-170.
161. Freed LE, Grande DA, Lingbin Z, et al. Joint resurfacing using allograft chondrocytes and synthetic biodegradable polymer scaffolds. J Biomed Mater Res 1994; 28: 891-899.
162. Perka C, Sittinger M, Schultz O, et al. Tissue engineered cartilage repair using cryopreserved and noncryopreserved chondrocytes. Clin Orthop 2000; 378: 245-254.
163. Schaefer D, Martin I, Jundt G, et al. Tissue-engineered composites for the repair of large osteochondral defects. Arthritis Rheum 2002; 46: 2524-2534.
164. Goomer RS, Deftos LJ, Terkeltaub R, et al. High-efficiency non-viral transfection of primary chondrocytes and perichondrial cells for ex-vivo gene therapy to repair articular cartilage defects. Osteoarthritis Cartilage 2001; 9: 248-256.
165. Ueblacker P, Wagner B, Kruger A, et al. Inducible nonviral gene expression in the treatment of osteochondral defects. Osteoarthritis Cartilage 2004; 12: 711-719.
166. Pascher A, Palmer GD, Steinert A, et al. Gene delivery to cartilage defects using coagulated bone marrow aspirate. Gene Ther 2004; 11: 133-141.
167. Mierisch CM, Wilson HA, Turner MA, et al. Chondrocyte transplantation into articular cartilage defects with use of calcium alginate: the fate of the cells. J Bone Joint Surg Am 2003; 85-A: 1757-1767.
168. Kobayashi N, Koshino T, Uesugi M, et al. Gene marking in adeno-associated virus vector infected periosteum derived cells for cartilage repair. J Rheumatol 2002; 29: 2176-2180.
169. Hidaka C, Goodrich LR, Chen CT, et al. Acceleration of cartilage repair by genetically modified chondrocytes over expressing bone morphogenetic protein-7. J Orthop Res 2003; 21: 573-583.
170. Sellers RS, Zhang R, Glasson SS, et al. Repair of articular cartilage defects one year after treatment with recombinant human bone morphogenetic protein-2 (rhBMP-2). J Bone Joint Surg Am 2000; 82: 151-160.
171. Wakitani S, Kimura T, Hirooka A, et al. Repair of rabbit articular surfaces with allograft chondrocytes embedded in collagen gel. J Bone Joint Surg Br 1989; 71: 74-80.
172. Mason JM, Breitbart AS, Barcia M, et al. Cartilage and bone regeneration using gene-enhanced tissue engineering. Clin Orthop 2000; 379: S171-178.
173. Soon-Shiong P, Heintz RE, Merideth N, et al. Insulin independence in a type 1 diabetic patient after encapsulated islet transplantation. Lancet 1994; 343: 950-951.
174. Schek RM, Hollister SJ, Krebsbach PH. Delivery and protection of adenoviruses using biocompatible hydrogels for localized gene therapy. Mol Ther 2004; 9: 130-138.
175. Jeschke MG, Barrow RE, Hawkins HK, et al. Effect of multiple gene transfers of insulinlike growth factor I complementary DNA gene constructs in rats after thermal injury. Arch Surg 1999; 134: 1137-1141.
176. Hunziker EB. Biologic repair of articular cartilage. Defect models in experimental animals and matrix requirements. Clin Orthop 1999; 367: S135-146.