Gene transfer in tissue repair: Status, challenges and future directions

Expert Opinion on Biological Therapy

Volumn 4, Issue 9, 2004, Pages 1373-1386

  Eming, Sabine A ^a   Krieg, Thomas ^a   Davidson, Jeffrey M ^b,c  

^a UNIVERSITY OF COLOGNE   (Germany)

^b VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

Gene transfer; Growth factors; Wound healing

Indexed keywords

ADENOVIRUS VECTOR; ANKYRIN; BONE MORPHOGENETIC PROTEIN; COLCHICINE; DECORIN; EPIDERMAL GROWTH FACTOR; GENE PRODUCT; GROWTH FACTOR; HERPESVIRUS VECTOR; HYPOXIA INDUCIBLE FACTOR 1; LIPOSOME; MICROSPHERE; NITRIC OXIDE; PARVOVIRUS VECTOR; PLASMID DNA; POLYMER; POLYPEPTIDE; RECOMBINANT CARDIAC ANKYRIN REPEAT PROTEIN; RECOMBINANT GROWTH FACTOR; RECOMBINANT HYPOXIA INDUCIBLE FACTOR 1; RECOMBINANT INDUCIBLE NITRIC OXIDE SYNTHASE; RECOMBINANT INTERLEUKIN 1 RECEPTOR BLOCKING AGENT; RECOMBINANT OSTEOGENIC PROTEIN 1; RECOMBINANT PLATELET DERIVED GROWTH FACTOR; RECOMBINANT PLATELET DERIVED GROWTH FACTOR B; RECOMBINANT PROTEIN; RECOMBINANT SCATTER FACTOR; RECOMBINANT SMAD PROTEIN; RECOMBINANT SOMATOMEDIN C; RECOMBINANT VASCULOTROPIN; RECOMBINANT VASCULOTROPIN 165; RETROVIRUS VECTOR; SMAD PROTEIN; UNCLASSIFIED DRUG;

CARTILAGE; CARTILAGE CELL; CELL ACTIVITY; CELL TYPE; CLINICAL TRIAL; CULTURE MEDIUM; DEVICE; DNA MODIFICATION; DRUG DELIVERY SYSTEM; EX VIVO GENE TRANSFER; EX VIVO STUDY; EXTRACELLULAR MATRIX; GAM501 GENE; GENE; GENE ACTIVATED MATRIX; GENE DELIVERY MEDIUM; GENE EXPRESSION REGULATION; GENE TARGETING; GENE TARGETING DEVICE; GENE TRANSFER; GENETICALLY MODIFIED CELL; GROWTH FACTOR GENE; HETEROLOGOUS REGULATIVE GENE EXPRESSION SYSTEM; HUMAN; IL 1RA GENE; IN VIVO GENE TRANSFER; IN VIVO STUDY; INOS GENE; KERATINOCYTE; LIGAMENT; MEDIATOR; MESENCHYME CELL; MOLECULAR GENETICS; MOLECULE; NERVE; NONHUMAN; NONVIRAL GENE DELIVERY SYSTEM; PERIPHERAL VASCULAR DISEASE; REVIEW; SKIN; SKIN FIBROBLAST; SOFT TISSUE; TECHNIQUE; TENDON; TISSUE REGENERATION; TISSUE REPAIR; TOPICAL DRUG ADMINISTRATION; TRANSGENE; TRANSGENE EXPRESSION REGULATION; VIRAL GENE DELIVERY SYSTEM; VIRUS RECOMBINANT; WOUND HEALING;

ADENOVIRIDAE; ANIMALS; DEPENDOVIRUS; DNA, RECOMBINANT; FORECASTING; GENE EXPRESSION REGULATION; GENE TRANSFER TECHNIQUES; GENETIC VECTORS; GROWTH SUBSTANCES; HERPESVIRUS 1, HUMAN; HUMANS; LIGAMENTS; LIPOSOMES; ORGAN SPECIFICITY; REGENERATION; RETROVIRIDAE; SIGNAL TRANSDUCTION; SKIN; SOFT TISSUE INJURIES; TENDON INJURIES; WOUND HEALING; WOUNDS AND INJURIES;

ADENOVIRIDAE; HERPESVIRIDAE; PARVOVIRUS; UNIDENTIFIED RETROVIRUS;

EID: 4544365089     PISSN: 14712598     EISSN: None     Source Type: Journal    
DOI: 10.1517/14712598.4.9.1373     Document Type: Review

References (129)

1. MARTIN P: Wound healing - aiming for perfect skin regeneration. Science (1997) 276:75-81 A thorough review of the biology in wound repair.
2. SINGER AJ, CLARK RA: Cutaneous wound healing. N. Engl. J. Med. (1999) 341:738-746.
3. WERNER S, GROSE R: Regulation of wound healing by growth factors and cytokines. Physiol. Rev. (2003) 83:835-870.
4. SCHEID A, MEULI M, GASSMANN M, WENGER RH: Genetically modified mouse models in studies on cutaneous wound healing. Exp. Physiol. (2000) 85:687-704. A comprehensive survey on transgenetic mouse models in cutaneous wound healing.
5. STEED DL: Modifying the wound healing response with exogenous growth factors. Clin. Plast. Surg. (1998) 25:397-405.
6. SCHARFFETTER-KOCHANEK K, MEEWES C, EMING SA et al: Chronische Wunden und Wachstumsfaktoren. Z Hautkrankheiten (1999) 74:664-672.
7. WENK J, FOITZIK A, ACHTERBERG V et al.: Selective pick-up of increased iron by deferoxamine-coupled cellulose abrogates the iron-driven induction of MMP-1 and lipid peroxidation in human dermal fibroblasts in vitro: a new dressing concept. J. Invest. Dermatol. (2001) 116:833-839.
8. GRINNELL F, HO CH, WYSOCKI A: Degradation of fibronectin and vitronectinin chronic wound fluid: analysis by cell blotting, immunoblotting, cell adhesion assays J. Invest. Dermatol. (1992) 98:410-416.
9. GRINNELL F, ZHU M: Fibronectin degradation in chronic wounds depends on the relative levels of elastase, alpha1-proteinase inhibitor, and alpha2-macroglobulin. J. Invest. Dermatol. (1996) 106:335-341.
10. BARRICK B, CAMPBELL EJ, OWEN CA: Leukocyte proteinases in wound healing: roles in physiologic and pathologic processes. Wound Repair Regen. (1999) 7:410-422. A thorough review of leukocyte proteases in wound repair.
11. WECKROTH M, VAHERI A, LAUHARANTA J, SORSA T, KONTTINEN YT: Matrix metalloproteinases, gelatinase and collagenase in chronic leg ulcers. J. Invest. Dermatol. (1996) 106:1119-1124.
12. WLASCHEK M, PEUS D, ACHTERBERG V, MEYER-INGOLD W, SCHARFFETTER-KOCHANEK K: Protease inhibitors protect growth factor activity in chronic wounds. Br. J. Dermatol. (1997) 137:646.
13. LAUER G, SOLBERG S, COLE M et al.: Expression and proteolysis of VEGF is increased in chronic wounds. J. Invest. Dermatol. (2000) 115:12-18.
14. HOFFMAN R, STARKEY S, COAD J: Wound fluid from venous leg ulcers degrades plasminogen and reduces plasmin generation by keratinocytes. J. Invest. Dermatol. (1998) 111:1140-1144.
15. WALLACE HJ, STACEY MC: Levels of TNF-α and soluble TNF receptors in chronic venous leg ulcers - correlation to healing status. J. Invest. Dermatol. (1998) 110:292-296.
16. AEPFELBACHER MA, ESSLER M, HUBER E et al.: Bacterial toxins block endothelial wound repair. Arterioscler. Thromb. Vasc. Biol. (1997) 17:1623-1629.
17. BOWLER PG: Wound pathophysiology, infection and therapeutic options. Ann. Med. (2002) 34:419-427.
18. BARBIERI JT: Pseudomonas aeruginosa exoenzyme S, a bifunctional type-III secreted cytotoxin. Int. J. Med. Microbiol. (2000) 290:381-387.
19. KÖRBLING M, ESTROV Z: Adult stem cells for tissue repair - a new therapeutic concept? N. Engl. J. Med. (2003) 349:570-582. Retrospective evaluation of various models of adult stem cells derived from bone marrow and peripheral blood, and their potential therapeutic applications.
20. VACANTI JP, LANGER R: Tissue engineering: the design and fabrication of living replacement devices for surgical reconstruction and transplantation. Lancet (1999) 354(Suppl. 1):32-34.
21. ANGER R: Biomaterials in drug delivery and tissue engineering: one laboratory's experience. Acc. Chem. Res. (2000) 33:94-101.
22. MULLIGAN RC: The basic science of gene therapy. Science (1993) 260:926-932.
23. LEVINE F, FRIEDMANN T: Gene therapy. Am. J. Dis. Child. (1993) 147:1167-1174.
24. KHAVARI PA: Therapeutic gene delivery to the skin. Mol. Med. Today (1997) 3:533-538. A detailed evaluation of gene delivery strategies in skin.
25. KHAVARI PA, KRUEGER GG: Cutaneous gene delivery. Adv. Clin. Res. (1997) 5:27-35.
26. KOOTSTRA NA, VERMA IM: Gene therapy with viral vectors. Annu. Rev. Pharmacol. Toxicol. (2003) 43:413-439. A thorough review of viral vectors used for gene therapy.
27. FRIEDMANN T: A brief history of gene therapy. Nat. Genet. (1992) 2:93-98.
28. MORGAN JR, TOMPKINS RG, YARMUSH ML: Advances in recombinant retroviruses for gene delivery. Adv. Drug Deliv. Rev. (1993) 12:143-158. A detailed survey on retroviral biology.
29. LEDOUX JM, LANDAZURI N, YARMUSH ML, MORGAN JR: Complexation of retrovirus with cationic and anionic polymers increases the efficiency of gene transfer. Hum. Gene Ther. (2001) 12:1611-1621.
30. NALDINI L, BLÖMER U, GALLAY P et al.: In vivo delivery and stable transduction of nondividing cells by a lentiviral vector. Science (1996) 272:263-267.
31. KUHN U, TERUNUMA A, PFUTZNER W, FOSTER RA, VOGEL JC: In vivo assessment of gene delivery to kerarinocytes by lentiviral vectors. J. Virol. (2002) 76:1496-1504.
32. SIPRASHVILI Z, KHAVARI PA: Lentivectors for regulated and reversible cutaneous gene delivery. Mol. Ther. (2004) 9:93-100.
33. PALMER TD, ROSMAN GJ, OSBORNE WR, MILLER AD: Genetically modified skin fibroblasts persist long after transplantation but gradually inactivate introduced genes. Proc. Natl. Acad. Sci. USA (1991) 88:1330-1334.
34. ROEMER K, FRIEDMANN T: Concepts and strategies for human gene therapy. Eur. J. Biochem. (1992) 208:211-225.
35. CHALLITA PM, KOHN DB: Lack of expression from retroviral vector after transduction of murine hematopoetic stem cells is associated with methylation in vivo. Proc. Natl. Acad. Sci. USA (1994) 91:2567-2571.
36. DANOS O, MULLIGAN R: Safe and efficient generation of recombinant retroviruses with amphotropic and ecotropic host ranges. Proc. Natl. Acad. Sci. USA (1988) 85:6460-6464.
37. HACEIN-BEY-ABINA S, VON KALLE C, SCHMIDT M et al.: A serious adverse event after successful gene therapy for X-linked severe combined immunodeficiency. N. Engl. J. Med. (2003) 348:255-256. Retroviral vector-induced target cell transformation in human gene therapy trial.
38. MARSHALL E: Second child in French trial is found to have leukemia. Science (2003) 299:320. Retroviral vector-induced target cell transformation in human gene therapy trial.
39. TERSKIKH VV, VASILIEV AV: Cultivation and transplantation of epidermal keratinocytes. Int. Rev. Cytol. (1999) 188:41-72.
40. BURT AM, PALLETT CD, SLOANE JP et al.: Survival of cultured allografts in patients with burns assessed with probe specific for y chromosomes. Br. Med. J. (1989)298:915-917. Clinical study evaluating survival of cultured epithelial allografts.
41. WILSON JM: Adenovirus as gene-delivery vehicles. N. Engl. J. Med. (1996) 334:1185-1187.
42. WANG Q, FINER MH: Second-generation adenovirus vectors. Nat. Med. (1996) 2:714-716.
43. SCHIEDNER G, MORAL N, PARKS RJ et al.: Genomic DNA transfer with high-capacity adenovirus vector results in improved in vivo gene expression and decreased toxicity. Nat. Genet. (1998) 18:180-183.
44. KAFRI T, MORGAN D, KRAHL D, SARVETNICK N, SHERMAN L, VERMA I: Cellular immune response to adenoviral vector infected cells does not require de novo viral gene expression: implications for gene therapy. Proc. Natl. Acad. Sci. USA (1998) 95:11377-11382.
45. MONAHAN PE, SAMULSKI RJ: AAV vectors: is clinical success on the horizon? Gene Ther. (2000) 7:24-30.
46. ROIZMAN B: The function of HSV genes: a primer for genetic engineering of novel vectors. Proc. Natl. Acad. Sci. USA (1996) 93:11307-11312.
47. GLORIOSO JC, GOINS WF, SCHMIDT MC et al.: Engineering HSV vectors for human gene therapy. Adv. Pharmacol. (1997) 40:103-136.
48. YAO F, ERIKSSON E: A novel anti-HSV type 1 specific HSV type 1 recombinant. Hum. Gene Ther. (1999) 10:1811-1818.
49. COSTANTINI LC, BAKOWSKA JC, BREAKEFILD XO, ISACSON O: Gene therapy in the CNS. Gene Ther. (2000) 7:93-109.
50. FELGNER PL, RHODES G: Gene therapeutics. Nature (1991) 349:351-352.
51. ORITZ-URDA S, THYAGARAJAN B, KEENE DR et al.: Stable nonviral genetic correction of inherited human skin disease. Nat. Med. (2002) 8:1166-1171. Novel approach to non-viral stable genomic integration of large DNA sequences using the φ31 bacteriophage integrase.
52. HENGGE UR, CHAN EF, FOSTER RA, WALKER PS, VOGEL JC: Cytokine gene expression in epidermis with both biological effects following injection of naked DNA. Nat. Genet. (1995) 10:161-166. Direct injection of plasmid DNA into pig skin results in transient expression of a biologically active factor in the epidermis.
53. SUN L, XU L, CHANG H et al.: Transfection with aFGF cDNA improves wound healing. J. Invest. Dermatol. (1997) 108:313-318.
54. MEULI M, LIU Y, LIGGITT D et al.: Efficient gene expression in skin wound sites following local plasmid injection. J. Invest. Dermatol. (2001) 131:131-135.
55. SAWAMURA D, YASUKAWA K, KODAMA K et al.: The majority of keratinocytes incorporate intradermally injected plasmid DNA regardless of size but only a small proportion of cells can express the gene product. J. Invest. Dermatol. (2002) 118:967-971.
56. CIERNIK IF, KRAYENBÜHL BH, CARBONE DP: Puncture-mediated gene transfer to the skin. Hum. Gene Ther. (1996) 7:893-899.
57. ERIKSSON E, YAO F, SVENSJÖ T et al.: In vivo gene transfer to skin and wound by microseeding. J. Surg. Res. (1998) 78:85-91.
58. KLEIN TM, WOLF ED, WU R, SANFORD JC: High-velocity microprojectiles for delivering nucleic acids into living cells. Nature (1987) 327:70-73.
59. YANG NS, BURKHOLDER J, ROBERTS B, MARTINELL B, MCCABE D: In vivo and in vitro gene transfer to mammalian somatic cells by particle bombardment. Proc. Natl. Acad. Sci. USA (1990) 87:9568-9572.
60. WILLIAMS RS, JOHNSTON SA, RIEDY M, DEVIT MJ, MCELLIGOT SG, SANFORD JC: Introduction of foreign genes into tissues of living mice by DNA-coated microprojectiles. Proc. Natl. Acad. Sci. USA (1991) 88:2726-2730.
61. CHENG L, ZIEGELHOFFER PR, YANG NS: In vivo promoter activity and transgene expression in mammalian somatic tissues evaluated by using particle bombardment. Proc. Natl. Acad. Sci. USA (1993) 90:4455-4459.
62. SUN WH, BURKHOLDER JK, SUN J et al.: In vivo cytokine gene transfer by gene gun reduces tumor growth in mice. Proc. Natl. Acad. Sci. USA (1995) 92:2889-2893.
63. YANG NS, SUN WH: Gene gun and other non-viral approaches for cancer gene therapy. Nat. Med. (1995) 1:481-483.
64. DAVIDSON JM, KRIEG T, EMING SA.: Particle-mediated gene therapy of wounds. Wound Repair Regen. (2000) 8:452-459.
65. FELGNER PL, RINGOLD GM: Canonic liposome-mediated transfection. Nature (1989) 337:387-388.
66. LI L, HOFFMAN RM: The feasibility of targeted selective gene therapy of the hair follicle. Nat. Genet. (1995) 1:705-706.
67. TRUBETSKOY VS, TORCHILIN VP, KENNEL S, HUANG L.: Cationic liposomes enhance targeted delivery and expression of exogenous DNA mediated by N-terminal modified poly(L-lysine)-antibody conjugate in mouse lung endothelial cells. Biochem. Biophys. Acta (1992) 1131:311-313.
68. EMING SA, MORGAN JR, BERGER A: Gene therapy for tissue repair approaches and prospects. Br. J. Plast. Surg. (1997) 50:491-500.
69. LA CAVA A, BILETTA R, GAIETTA G et al.: Cell-mediated DNA transport between distant inflammatory sites following intradermal DNA immunization in the presence of adjuvant. J. Immunol. (2000) 164:1340-1345.
70. BONADIO J: Tissue engineering via local gene delivery. J. Mol. Med. (2000) 78:303-311.
71. SHEA LD, SMILEY E, BONADIO J, MOONEY DJ: DNA delivery from polymer matrices for tissue engineering. Nat. Biotechnol. (1999) 17:551-554. Sustained delivery of plasmid DNA from poly(lactide-co-grycolide) matrices led to the transfection of large numbers of cells in vivo.
72. BONADIO J, SMILY E, PATIL P, GOLDSTEIN S: Localized, direct plasmid gene delivery in vivo: prolonged therapy results in reproducible tissue regeneration. Nat. Med. (1999) 5:753-759.
73. DOUKAS J, CHANDLER LA, GONZALES AM et al.: Matrix immobilization enhances the tissue repair activity of growth factor gene therapy vectors. Hum. Gene Ther. (2001) 12:783-798.
74. JAAKKOLA P, AHONEN M, KÄHÄRI VM, JALKANEN M: Transcriptional targeting of adenoviral gene delivery into migrating wound keratinocytes using FiRE, a growth factor-inducible regulatory element. Gene Ther. (2000) 7:1640-6147.
75. GOSSEN M, BUJARD H: Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc. Natl. Acad. Sci. USA (1992) 89:5547-5551.
76. GOSSEN M, FREUNDLIEB S, BENDER G, MULLER G, HILLEN W, BUJARD H: Transcriptional activation by tetracyclines in mammalian cells. Science (1995) 268:1766-1769.
77. NO D, YAO TP, EVANS RM: Ecdysone-inducible gene expression in mammalian cells and transgenic mice. Proc. Natl. Acad. Sci. USA (1996) 93:3346-3351.
78. WANG Y, O'MALLEY BW JR, TSAI SY, O'MALLEY BW: A regulatory system for use in gene transfer. Proc. Natl. Acad. Sci. USA (1994) 91:8180-8184.
79. WANG X, LIEFER K, TSAI SY, O'MALLEY BW, ROOP D: Development of gene-switch transgenic mice that inducibly express TGF-b1 in the epidermis. Proc. Natl. Acad. Sci. USA (1999) 96:8483-8488.
80. RIVERA VM, CLACKSON T, NATESAN S et al.: A humanized system for pharmacologic control of gene expression. Nat. Med. (1996) 2:1028-1032.
81. LIBERLES S, DIVER S, AUSTIN D, SCHREIBERS: Inducible gene expression and protein tanslocation using nontoxic ligands identified by mammalian three-hybrid screen. Proc. Natl. Acad. Sci. USA (1997) 94:7825-7830.
82. PFÜTZNER W, TERUNUMA A, TOCK CL et al.: Topical colchicine selection of keratinocytes transduced with the multidrug resistance gene (MDR1) can sustain and enhance transgene expression in vivo. Proc. Natl. Acad. Sci. USA (2002) 99:13096-13101.
83. KRUEGER GG, MORGAN JR, JORGENSEN CM: Modified skin to treat disease: potential and limitations. J. Invest. Dermatol. (1994) 103:76S-84S.
84. HENGGE UR, TAICHMAN LB, KAUR P et al.: How realistic is cutaneous gene therapy? Exp. Dermatol. (1999) 8:419-431.
85. EMING SA, LEE J, SNOW RG, TOMPKINS RG et al.: Genetically modified human epidermis overexpressing PDGF-A directs the development of a cellular and vascular connective tissue stroma when transplanted to athymic mice. J. Invest. Dermatol. (1995) 105:756-763.
86. EMING SA, SNOW RG, YARMUSH ML et al.: Targeted expression of IGF-1 to human keratinocytes: modification of the autocrine control of keratinocyte proliferation. J. Invest. Dermatol. (1996) 106:113-120.
87. EMING SA, MEDALIE DA, TOMPKINS RG, YARMUSH ML, MORGAN JR: Genetically modified human keratinocytes overexpressing PDGF-A enhance the performance of a composite skin graft. Hum. Gene Ther. (1998) 9:529-539.
88. MESRI EA, FEDEROFF HJ, BROWNLEE M: Expression of VEGF from a defective HSV-1 amplicon vector induces angiogenesis in mice. Circ. Res. (1995) 76:161-167.
89. BREITBART AS, MASON JM, URMACHER C et al.: Gene-enhanced tissue engineering: application for wound healing using cultured dermal fibroblasts transduced retrovirally with the PDGF-B gene. Ann. Plast. Surg. (1999) 43:632-639.
90. MACHENS HG, MORGAN JR, BERTHIAUME F, STEFANOVICH P, REIMER R, BERGER AC: Genetically modified fibroblasts induce angiogenesis in the rat epigastric island flap. Langenbecks Arch. Surg. (1998) 383:345-350.
91. ANDREE C, SWAIN WF, PAGE CP et al.: In vivo transfer and expression of a human epidermal growth factor gene accelerates wound repair. Proc. Natl. Acad. Sci. USA (1994) 91:12188-12192.
92. EMING SA, WHISITT JS, HE L, KRIEG T, MORGAN JR, DAVIDSON JM: Particle-mediated gene transfer of PDGF isoforms promotes wound repair. J. Invest. Dermatol. (1999) 112:297-302.
93. GHAZIZADEH S, HARRINGTHON R, TAICHMAN L: In vivo transduction of mouse epidermis with recombinant retroviral vectors: implications for cutaneous gene therapy. Gene Ther. (1999) 6:1267-1275.
94. GRUSS CJ, SATYAMOORTHY K, BERKING C: Stroma formation and angiogenesis by overexpression of growth factors, cytokines, and proteolytic enzymes in human skin grafted to SCID mice. J. Invest. Dermatol. (2003) 120:683-692.
95. BENN SI, WHITSITT JS, BROADLY KN et al.: Enhancement of wound healing in rat skin following particle bombardment with cDNAs encoding TGF-β1. J. Clin. Invest. (1996) 98:2894-2902.
96. JESCHKE MG, RICHTER G, HERNDON DN: Therapeutic success and efficacy of nonviral liposomal cDNA gene transfer to the skin in vivo is dose dependent. Gene Ther. (2001) 8:1777-1784.
97. YAMASAKI K, EDLINGTON HDJ, MCCLOSKY C et al.: Reversal of impaired wound repair in iNOS-deficient mice by topical adenoviral-mediated iNOS gene transfer. J. Clin. Invest. (1998) 101:967-971.
98. LIECHTY KW, MACKENZIE TC, SHAABAN AF et al.: Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep. Nat. Med. (2000) 6:1282-1286.
99. DESROSIERS EA, YAHIA L, RIVARD CH: Proliferative and matrix synthesis response of canine anterior cruciate ligament fibroblasts submitted to combined growth factors. J. Orthop. Res. (1996) 14:200-202.
100. HILDEBRAND KA, FRANK CB, HART DA: Gene intervention in ligament and tendon: current status, challenges, future directions. Gene Ther. (2004) 11:368-378.
101. NAKAMURA N, HART DA, BOORMAN RS et al.: Decorin antisense gene therapy improves functional healing of early rabbit ligament scar with enhanced collagen fibrillogenesis in vivo. J. Orthop. Res. (2000) 18:517-523.
102. NAKAMURA N, SHINO K, NATSUUME T: Early biological effect of in vivo gene transfer of PDGF-B into healing patellar ligament. Gene Ther. (1998) 5:1165-1170.
103. LOU J, TU Y, BURNS M, SILVA MJ, MANSKE P: BMP-12 gene transfer augmentation of lacerated tendon repair. J. Orthop. Res. (2001) 19:1199-1202.
104. FUJISATE T, SAJIKI T, LIU O et al.: Effects of bFGF on cartilage regeneration in chondrocyte-seeded collagen sponge scaffold. Biomateriats (1996) 17:155-162.
105. TRIPPEL SB, GHIVIZZANI SC, NIXON AJ: Gene-based approaches for the repair of articular cartilage. Gene Ther. (2004) 11:351-359.
106. BARAGI VM, RENKIEWICZ RR, JORDAN H et al.: Transplantation of transduced chondrocytes protects articular cartilage from IL-1 induced extracellular matrix degradation. J. Clin. Invest. (1995) 96:2454-2460.
107. MADRY H, CUCCHIARINI M, TERWILLIGER EF, TRIPPEL SB: Recombinant adeno-associated virus vectors efficiently and persistently transduce chondrocytes in normal and osteoarthritic human articular cartilage. Hum. Gene Ther. (2003) 14:393-402.
108. GOODRICH LR: Long-term biochemical analysis of articular cartilage repaired with genetically modified chondrocytes expressing IGF-1. Vet. Surg. (2003) 32:1-2.
109. HIDAKA C, GOODRICH LR, CHEN CT, WARREN RF, CRYSTAL RG, NIXON AJ: Acceleration of cartilage repair by genetically modified chondrocytes over expressing bone morphogenetic protein-7. J. Orthop. Res. (2003) 21:573-583.
110. LIECHTY KW, NESBIT M, HERLYN M, RADU A, ADZICK NS, CROMBLEHOLME TM: Adenoviral-mediated overexpression of PDGF-B corrects ischemic impaired wound healing. J. Invest. Dermatol. (1999) 113:375-383.
111. HAAS AR,TUAN RS: MurineC3H10T1/2 multipotential cells as an in vitro model of mesenchymal chondrogenesis. Methods Mol. Biol. (2000) 137:383-389.
112. MASON JM, GRANDE DA, BARCIA M, GRANT R, PERGOLIZZI RG, BREITBART AS: Expression of human bone morphogenic protein 7 in primary rabbit periostal cells: potential utility in gene therapy for osteochondral repair. Gene Ther. (1998) 5:1098-1104.
113. GELSE K, VON DER MARK K, AIGNER T, PARK J, SCHNEIDER H: Articular cartilage repair by gene therapy using growth factor-producing mesenchymal cells. Arthritis Rheum. (2003) 48:430-441.
114. ROBBINS PD, EVANS CH, CHERNAJOVSKY Y: Gene therapy for arthritis. Gene Ther. (2003) 10:902-911.
115. GLATZEL M, FLECHSING E, NAVARRO B et al.: Adenoviral and adeno-associated viral transfer of genes to the peripheral nervous system. Proc. Natl. Acad. Sci. USA (2000) 97:442-447.
116. ZHANG F, LINEAWEAVER WC: Gene transfer with DNA strand technique and peripheral nerve injury. J. Long Term Eff. Med. Implants (2002) 12:85-96.
117. SHY ME, TANI M, SHI YJ et al.: An adenoviral vector can transfer lacZ expression into Schwann cells in culture and sciatic nerve. Ann. Neurol. (1995) 38:429-436.
118. SORENSEN J, HAASE G, KRARUP C et al.: Gene transfer to Schwann cells after peripheral nerve injury: a delivery system for therapeutic agents. Ann. Neurol. (1998) 43:205-211.
119. SAKAMOTO T, WATABE K, OHASHI T et al.: Adenoviral vector mediated GDNF gene transfer prevents death of adult facial motoneurons. Neuroreport (2000) 11:1857-1869.
120. TERASAKI K, KANZAKI T, OKU T, SHINAGAWA A: Recombinant human tissue inhibitor of MMP-2 (rhTIMP-2) accelerated wound healing. J. Invest. Dermatol. (1996) 107:517-523.
121. LAUER G, SOLBERG S, COLE M, KRIEG T, EMING SA: Generation of a novel proteolysis resistant VEGF165 variant by a site-directed mutation at the plasmin sensitive cleavage site. FEBS Lett. (2002) 531:309-313. Mutation at the plasmin cleavage site increases VEGF165 stability and activity at the chronic wound site.
122. ERDAG G, MORGAN JR: IL-1a and IL-6 enhance the antibacterial properties of cultured composite keratinocyte grafts. Ann. Surg. (2002) 235:113-124.
123. ELSON DA, THURSTON G, HUANG LE et al.: Induction of hypervascularity without leakage or inflammation in transgenic mice overexpressing hypoxia-inducible factor-1alpha. Genes Dev. (2001) 15:2520-32.
124. BRADDOCK M: The transcription factor Egr-1: a potential drug in wound healing and tissue repair. Ann. Med. (2001) 33:313-318.
125. DAVIDSON JM: Cardiac ankyrin repeat protein (CARP): transcriptional regulation and neovascularization. Am. J. Pathol. (2004) (In Press).
126. DE CROMBRUGGHE B, LEFEBVRE V, BEHRINGER RR, BI W, MURAKAMI S, HUANG W: Transcriptional mechanisms of chondrocyte differentiation. Matrix Biol. (2000) 19:389-394.
127. WATANABE H, DE CAESTECKER MP, YAMADA Y: Transcriptional crosstalk between Smad, ERK1/2, and p38 mitogen activated protein kinase pathways regulates TGF-b-induced aggrecan gene expression in chondrogenic ATDC5 cells. J. Biol. Chem. (2001) 276:14466-14473.
128. ASHCROFT GS, YANG X, GLICK AB et al.: Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory response. Nat. Cell Biol. (1999) 1:260-266.
129. SOHN YD, LIM HJ, HWANG KC et al.: A novel recombinant basic FGF and its secretion. Biochem. Biophys. Res. Commun. (2001) 284:931-936.