Skip to main content

Gene Therapy for Cartilage Tissue Engineering

  • Chapter
  • First Online:
Gene Therapy for Cartilage and Bone Tissue Engineering

Part of the book series: SpringerBriefs in Bioengineering ((BRIEFSBIOENG))

  • 1041 Accesses

Abstract

Gene therapy has converged with cartilage engineering in recent years, by which an increasing number of therapeutic genes have been explored to stimulate cartilage repair. These genes can be administered to cells via in vivo or ex vivo approaches using either viral or nonviral vectors. This chapter reviews various growth factors and delivery approaches under investigation.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 49.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 64.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Wei Y, Hu Y, Lv R, Li D (2006) Regulation of adipose-derived adult stem cells differentiating into chondrocytes with the use of rhBMP-2. Cytotherapy 8:570–579

    Google Scholar 

  2. Miljkovic N, Cooper G, Marra K (2008) Chondrogenesis, bone morphogenetic protein-4 and mesenchymal stem cells. Osteoarthritis Cartilage 16:1121–1130

    Google Scholar 

  3. Kuroda R, Usas A, Kubo S, Corsi K, Peng H, Rose T et al (2006) Cartilage repair using bone morphogenetic protein 4 and muscle-derived stem cells. Arthritis Rheum 54:433–442

    Google Scholar 

  4. Kemmis CM, Vahdati A, Weiss HE, Wagner DR (2010) Bone morphogenetic protein 6 drives both osteogenesis and chondrogenesis in murine adipose-derived mesenchymal cells depending on culture conditions. Biochem Biophys Res Commun 401:20–25

    Google Scholar 

  5. Vukicevic S, Grgurevic L (2009) BMP-6 and mesenchymal stem cell differentiation. Cytokine Growth Factor Rev 20:441–448

    Google Scholar 

  6. Pagnotto MR, Wang Z, Karpie JC, Ferretti M, Xiao X, Chu CR (2007) Adeno-associated viral gene transfer of transforming growth factor-β1 to human mesenchymal stem cells improves cartilage repair. Gene Ther 14:804–813

    Google Scholar 

  7. Han Y, Wei Y, Wang S, Song Y (2010) Cartilage regeneration using adipose-derived stem cells and the controlled-released hybrid microspheres. Joint Bone Spine 77:27–31

    Google Scholar 

  8. Jin X, Sun Y, Zhang K, Wang J, Shi T, Ju X et al (2007) Ectopic neocartilage formation from predifferentiated human adipose derived stem cells induced by adenoviral-mediated transfer of hTGF beta2. Biomaterials 28:2994–3003

    Google Scholar 

  9. Bouffi C, Thomas O, Bony C, Giteau A, Venier-Julienne M-C, Jorgensen C et al (2010) The role of pharmacologically active microcarriers releasing TGF-β3 in cartilage formation in vivo by mesenchymal stem cells. Biomaterials 31:6485–6493

    Google Scholar 

  10. Hennig T, Lorenz H, Thiel A, Goetzke K, Dickhut A, Geiger F et al (2007) Reduced chondrogenic potential of adipose tissue derived stromal cells correlates with an altered TGFbeta receptor and BMP profile and is overcome by BMP-6. J Cell Physiol 211:682–691

    Google Scholar 

  11. Feng G, Wan Y, Balian G, Laurencin CT, Li X (2008) Adenovirus-mediated expression of growth and differentiation factor-5 promotes chondrogenesis of adipose stem cells. Growth Factors 26:132–142

    Google Scholar 

  12. Fan H, Tao H, Wu Y, Hu Y, Yan Y, Luo Z (2010) TGF-beta3 immobilized PLGA-gelatin/chondroitin sulfate/hyaluronic acid hybrid scaffold for cartilage regeneration. J Biomed Mater Res A 95:982–992

    Google Scholar 

  13. Barry F, Boynton RE, Liu B, Murphy JM (2001) Chondrogenic differentiation of mesenchymal stem cells from bone marrow: differentiation-dependent gene expression of matrix components. Exp Cell Res 268:189–200

    Google Scholar 

  14. Estes BT, Wu AW, Guilak F (2006) Potent induction of chondrocytic differentiation of human adipose-derived adult stem cells by bone morphogenetic protein 6. Arthritis Rheum 54:1222–1232

    Google Scholar 

  15. Moioli EK, Hong L, Mao JJ (2007) Inhibition of osteogenic differentiation of human mesenchymal stem cells. Wound Repair Regen 15:413–421

    Google Scholar 

  16. Tang QO, Shakib K, Heliotis M, Tsiridis E, Mantalaris A, Ripamonti U (2009) TGF-beta3: a potential biological therapy for enhancing chondrogenesis. Expert Opin Biol Ther 9:689–701

    Google Scholar 

  17. Mehlhorn AT, Niemeyer P, Kaschte K, Muller L, Finkenzeller G, Hartl D et al (2007) Differential effects of BMP-2 and TGF-beta1 on chondrogenic differentiation of adipose derived stem cells. Cell Prolif 40:809–823

    Google Scholar 

  18. Shen B, Wei A, Tao H, Diwan AD, Ma DD (2009) BMP-2 enhances TGF-beta3-mediated chondrogenic differentiation of human bone marrow multipotent mesenchymal stromal cells in alginate bead culture. Tissue Eng Part A 15:1311–1320

    Google Scholar 

  19. Lim SM, Oh SH, Lee HH, Yuk SH, Im GI, Lee JH (2010) Dual growth factor-releasing nanoparticle/hydrogel system for cartilage tissue engineering. J Mater Sci Mater Med 21:2593–2600

    Google Scholar 

  20. Otsuki S, Hanson SR, Miyaki S, Grogan SP, Kinoshita M, Asahara H et al (2010) Extracellular sulfatases support cartilage homeostasis by regulating BMP and FGF signaling pathways. Proc Natl Acad Sci U S A 107:10202–10207

    Google Scholar 

  21. Puetzer JL, Petitte JN, Loboa EG (2010) Comparative review of growth factors for induction of three-dimensional in vitro chondrogenesis in human mesenchymal stem cells isolated from bone marrow and adipose tissue. Tissue Eng Part B Rev 16:435–444

    Google Scholar 

  22. Nixon AJ, Haupt JL, Frisbie DD, Morisset SS, McIlwraith CW, Robbins PD et al (2005) Gene-mediated restoration of cartilage matrix by combination insulin-like factor-I/interleukin-1 receptor antagonist therapy. Gene Ther 12:177–186

    Google Scholar 

  23. Aghaloo T, Cowan CM, Chou YF, Zhang X, Lee H, Miao S et al (2006) Nell-1-induced bone regeneration in calvarial defects. Am J Pathol 169:903–915

    Google Scholar 

  24. Lee M, Siu RK, Ting K, Wu BM (2010) Effect of Nell-1 delivery on chondrocyte proliferation and cartilaginous extracellular matrix deposition. Tissue Eng Part A 16:1791–1800

    Google Scholar 

  25. Bi WM, Deng JM, Zhang ZP, Behringer RR, de Crombrugghe B (1999) Sox9 is required for cartilage formation. Nat Genet 22:85–89

    Google Scholar 

  26. Cao L, Yang F, Liu G, Yu D, Li H, Fan Q et al (2011) The promotion of cartilage defect repair using adenovirus mediated Sox9 gene transfer of rabbit bone marrow mesenchymal stem cells. Biomaterials 32:3910–3920

    Google Scholar 

  27. Lee J-M, Im G-I (2012) SOX trio-co-transduced adipose stem cells in fibrin gel to enhance cartilage repair and delay the progression of osteoarthritis in the rat. Biomaterials 33:2016–2024

    Google Scholar 

  28. Ghivizzani SC, Lechman ER, Tio C, Mule KM, Chada S, McCormack JE et al (1997) Direct retrovirus-mediated gene transfer to the synovium of the rabbit knee: implications for arthritis gene therapy. Gene Ther 4:977–982

    Google Scholar 

  29. Ulrich-Vinther M, Duch MR, Soballe K, O’Keefe RJ, Schwarz EM, Pedersen FS (2004) In vivo gene delivery to articular chondrocytes mediated by an adeno-associated virus vector. J Orthop Res 22:726–734

    Google Scholar 

  30. Lechman ER, Jaffurs D, Ghivizzani SC, Gambotto A, Kovesdi I, Mi ZB et al (1999) Direct adenoviral gene transfer of viral IL-10 to rabbit knees with experimental arthritis ameliorates disease in both injected and contralateral control knees. J Immunol 163:2202–2208

    Google Scholar 

  31. Oligino T, Ghivizzani SC, Wolfe D, Lechman ER, Krisky D, Mi Z et al (1999) Intra-articular delivery of a herpes simplex virus IL-1Ra gene vector reduces inflammation in a rabbit model of arthritis. Gene Ther 6:1713–1720

    Google Scholar 

  32. Pan RY, Chen SL, Xiao X, Liu DW, Peng HJ, Tsao YP (2000) Therapy and prevention of arthritis by recombinant adeno-associated virus vector with delivery of interleukin-1 receptor antagonist. Arthritis Rheum 43:289–297

    Google Scholar 

  33. Gouze E, Pawliuk R, Pilapil C, Gouze JN, Fleet C, Palmer GD et al (2002) In vivo gene delivery to synovium by lentiviral vectors. Mol Ther 5:397–404

    Google Scholar 

  34. Frisbie DD, Ghivizzani SC, Robbins PD, Evans CH, McIlwraith CW (2002) Treatment of experimental equine osteoarthritis by in vivo delivery of the equine interleukin-1 receptor antagonist gene. Gene Ther 9:12–20

    Google Scholar 

  35. Mease PJ, Wei N, Fudman EJ, Kivitz AJ, Schechtman J, Trapp RG et al (2010) Safety, tolerability, and clinical outcomes after intraarticular injection of a recombinant adeno-associated vector containing a tumor necrosis factor antagonist gene: results of a phase 1/2 study. J Rheumatol 37:692–703

    Google Scholar 

  36. Mease P, Wei N, Fudman E, Kivitz A, Schechtman J, Trapp R et al (2008) Safety and clinical outcomes after intra-articular administration of a recombinant adeno-associated vector containing a TNF antagonist gene. Arthritis Rheum 58:S433–S434

    Google Scholar 

  37. Mi ZB, Ghivizzani SC, Lechman ER, Jaffurs D, Glorioso JC, Evans CH et al (2000) Adenovirus-mediated gene transfer of insulin-like growth factor 1 stimulates proteoglycan synthesis in rabbit joints. Arthritis Rheum 43:2563–2570

    Google Scholar 

  38. Mi Z, Ghivizzani SC, Lechman E, Glorioso JC, Evans CH, Robbins PD (2003) Adverse effects of adenovirus-mediated gene transfer of human transforming growth factor beta 1 into rabbit knees. Arthritis Res Ther 5:R132–R139

    Google Scholar 

  39. Watanabe S, Imagawa T, Boivin GP, Gao GP, Wilson JM, Hirsch R (2000) Adeno-associated virus mediates long-term gene transfer and delivery of chondroprotective IL-4 to murine synovium. Mol Ther 2:147–152

    Google Scholar 

  40. Cucchiarini M, Madry H, Ma C, Thurn T, Zurakowski D, Menger MD et al (2005) Improved tissue repair in articular cartilage defects in vivo by rAAV-mediated overexpression of human fibroblast growth factor 2. Mol Ther 12:229–238

    Google Scholar 

  41. Cucchiarini M, Thurn T, Weimer A, Kohn D, Terwilliger EF, Madry H (2007) Restoration of the extracellular matrix in human osteoarthritic articular cartilage by overexpression of the transcription factor SOX9. Arthritis Rheum 56:158–167

    Google Scholar 

  42. Cucchiarini M, Orth P, Madry H (2013) Direct rAAV SOX9 administration for durable articular cartilage repair with delayed terminal differentiation and hypertrophy in vivo. J Mol Med 91:625–636

    Google Scholar 

  43. Gouze E, Pawliuk R, Gouze JN, Pilapil C, Fleet C, Palmer GD et al (2003) Lentiviral-mediated gene delivery to synovium: potent intra-articular expression with amplification by inflammation. Mol Ther 7:460–466

    Google Scholar 

  44. Moreland LW, Baumgartner SW, Schiff MH, Tindall EA, Fleischmann RM, Weaver AL et al (1997) Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein. N Engl J Med 337:141–147

    Google Scholar 

  45. Moreland LW (1998) Soluble tumor necrosis factor receptor (p75) fusion protein (ENBREL) as a therapy for rheumatoid arthritis. Rheum Dis Clin North Am 24:579–591

    Google Scholar 

  46. Evans CH, Ghivizzani SC, Robbins PD (2008) Arthritis gene therapy’s first death. Arthritis Res Ther 10:110

    Google Scholar 

  47. Frank KM, Hogarth DK, Miller JL, Mandal S, Mease PJ, Samulski RJ et al (2009) Brief report: investigation of the cause of death in a gene-therapy trial. N Engl J Med 361:161–169

    Google Scholar 

  48. Vinatier C, Mrugala D, Jorgensen C, Guicheux J, Noel D (2009) Cartilage engineering: a crucial combination of cells, biomaterials and biofactors. Trends Biotechnol 27:307–314

    Google Scholar 

  49. Gelse K, Schneider H (2006) Ex vivo gene therapy approaches to cartilage repair. Adv Drug Deliv Rev 58:259–284

    Google Scholar 

  50. Lieberman JR, Ghivizzani SC, Evans CH (2002) Gene transfer approaches to the healing of bone and cartilage. Mol Ther 6:141–147

    Google Scholar 

  51. Arai Y, Kubo T, Fushiki S, Mazda O, Nakai H, Iwaki Y et al (2000) Gene delivery to human chondrocytes by an adeno associated virus vector. J Rheumatol 27:979–982

    Google Scholar 

  52. Ulrich-Vinther M, Maloney MD, Goater JJ, Soballe K, Goldring MB, O’Keefe RJ et al (2002) Light-activated gene transduction enhances adeno-associated virus vector-mediated gene expression in human articular chondrocytes. Arthritis Rheum 46:2095–2104

    Google Scholar 

  53. Trippel SB, Ghivizzani SC, Nixon AJ (2004) Gene-based approaches for the repair of articular cartilage. Gene Ther 11:351–359

    Google Scholar 

  54. Gelse K, Jiang QJ, Aigner T, Ritter T, Wagner K, Poschl E et al (2001) Fibroblast-mediated delivery of growth factor complementary DNA into mouse joints induces chondrogenesis but avoids the disadvantages of direct viral gene transfer. Arthritis Rheum 44:1943–1953

    Google Scholar 

  55. Cottard V, Valvason C, Falgarone G, Lutomski D, Boissier MC, Bessis N (2004) Immune response against gene therapy vectors: influence of synovial fluid on adeno-associated virus mediated gene transfer to chondrocytes. J Clin Immunol 24:162–169

    Google Scholar 

  56. Gouze E, Gouze J-N, Palmer GD, Pilapil C, Evans CH, Ghivizzani SC (2007) Transgene persistence and cell turnover in the diarthrodial joint: implications for gene therapy of chronic joint diseases. Mol Ther 15:1114–1120

    Google Scholar 

  57. Madry H, Kaul G, Cucchiarini M, Stein U, Zurakowski D, Remberger K et al (2005) Enhanced repair of articular cartilage defects in vivo by transplanted chondrocytes overexpressing insulin-like growth factor I (IGF-I). Gene Ther 12:1171–1179

    Google Scholar 

  58. Hidaka C, Goodrich LR, Chen CT, Warren RF, Crystal RG, Nixon AJ (2003) Acceleration of cartilage repair by genetically modified chondrocytes overexpressing bone morphogenetic protein-7. J Orthop Res 21:573–583

    Google Scholar 

  59. Yokoo N, Saito T, Uesugi M, Kobayashi N, Xin K-Q, Okuda K et al (2005) Repair of articular cartilage defect by autologous transplantation of basic fibroblast growth factor gene-transduced chondrocytes with adeno-associated virus vector. Arthritis Rheum 52:164–170

    Google Scholar 

  60. Chen H-C, Chang Y-H, Chuang C-K, Lin C-Y, Sung L-Y, Wang Y-H et al (2009) The repair of osteochondral defects using baculovirus-mediated gene transfer with de-differentiated chondrocytes in bioreactor culture. Biomaterials 30:674–681

    Google Scholar 

  61. Zhang XL, Mao ZB, Yu CL (2004) Suppression of early experimental osteoarthritis by gene transfer of interleukin-1 receptor antagonist and interleukin-10. J Orthop Res 22:742–750

    Google Scholar 

  62. Evans CH, Robbins PD, Ghivizzani SC, Wasko MC, Tomaino MM, Kang R et al (2005) Gene transfer to human joints: progress toward a gene therapy of arthritis. Proc Natl Acad Sci U S A 102:8698–8703

    Google Scholar 

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

    Google Scholar 

  64. Gelse K, von der Mark K, Aigner T, Park J, Schneider H (2003) Articular cartilage repair by gene therapy using growth factor- producing mesenchymal cells. Arthritis Rheum 48:430–441

    Google Scholar 

  65. Zhu S, Zhang B, Man C, Ma Y, Hu J (2011) NEL-like molecule-1-modified bone marrow mesenchymal stem cells/poly lactic-co-glycolic acid composite improves repair of large osteochondral defects in mandibular condyle. Osteoarthritis Cartilage 19:743–750

    Google Scholar 

  66. Tsuchiya H, Kitoh H, Sugiura F, Ishiguro N (2003) Chondrogenesis enhanced by overexpression of sox9 gene in mouse bone marrow-derived mesenchymal stem cells. Biochem Biophys Res Commun 301:338–343

    Google Scholar 

  67. Lu C-H, Yeh T-S, Yeh C-L, Fang Y-HD, Sung L-Y, Lin S-Y et al (2014) Regenerating cartilages by engineered ASCs: prolonged TGF-β3/BMP-6 expression improved articular cartilage formation and restored zonal structure. Mol Ther 22:186–195

    Google Scholar 

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

    Google Scholar 

  69. Shuler FD, Georgescu HI, Niyibizi C, Studer RK, Mi Z, Johnstone B et al (2000) Increased matrix synthesis following adenoviral transfer of a transforming growth factor β1 gene into articular chondrocytes. J Orthop Res 18:585–592

    Google Scholar 

  70. Brower-Toland BD, Saxer RA, Goodrich LR, Mi ZB, Robbins PD, Evans CH et al (2001) Direct adenovirus-mediated insulin-like growth factor I gene transfer enhances transplant chondrocyte function. Hum Gene Ther 12:117–129

    Google Scholar 

  71. Obradovic B, Martin I, Padera RF, Treppo S, Freed LE, Vunjak-Novakovic G (2001) Integration of engineered cartilage. J Orthop Res 19:1089–1097

    Google Scholar 

  72. Martin I, Wendt D, Heberer M (2004) The role of bioreactors in tissue engineering. Trends Biotechnol 22:80–86

    Google Scholar 

  73. Chen H-C, Hu Y-C (2006) Bioreactors for tissue engineering. Biotechnol Lett 28:1415–1423

    Google Scholar 

  74. Darling EM, Athanasiou KA (2003) Articular cartilage bioreactors and bioprocesses. Tissue Eng 9:9–26

    Google Scholar 

  75. Portner R, Nagel-Heyer S, Goepfert C, Adamietz P, Meenen NM (2005) Bioreactor design for tissue engineering. J Biosci Bioeng 100:235–245

    Google Scholar 

  76. Madry H, Padera R, Seidel J, Langer R, Freed LE, Trippel SB et al (2002) Gene transfer of a human insulin-like growth factor I cDNA enhances tissue engineering of cartilage. Hum Gene Ther 13:1621–1630

    Google Scholar 

  77. Ho Y-C, Chen H-C, Wang K-C, Hu Y-C (2004) Highly efficient baculovirus-mediated gene transfer into rat chondrocytes. Biotechnol Bioeng 88:643–651

    Google Scholar 

  78. Chen H-C, Lee H-P, Sung M-L, Liao C-J, Hu Y-C (2004) A novel rotating-shaft bioreactor for two-phase cultivation of tissue-engineered cartilage. Biotechnol Prog 20:1802–1809

    Google Scholar 

  79. Chen H-C, Lee H-P, Ho Y-C, Sung M-L, Hu Y-C (2006) Combination of baculovirus-mediated gene transfer and rotating-shaft bioreactor for cartilage tissue engineering. Biomaterials 27:3154–3162

    Google Scholar 

  80. Sung L-Y, Lo W-H, Chiu H-Y, Chen H-C, Chuang C-K, Lee H-P et al (2007) Modulation of chondrocyte phenotype via baculovirus-mediated growth factor expression. Biomaterials 28:3437–3447

    Google Scholar 

  81. Smith P, Shuler FD, Georgescu HI, Ghivizzani SC, Johnstone B, Niyibizi C et al (2000) Genetic enhancement of matrix synthesis by articular chondrocytes: comparison of different growth factor genes in the presence and absence of interleukin-1. Arthritis Rheum 43:1156–1164

    Google Scholar 

  82. Dinser R, Kreppel F, Zaucke F, Blank C, Paulsson M, Kochanek S et al (2001) Comparison of long-term transgene expression after non-viral and adenoviral gene transfer into primary articular chondrocytes. Histochem Cell Biol 116:69–77

    Google Scholar 

  83. Madry H, Cucchiarini M, Terwilliger EF, Trippel SB (2003) Recombinant adeno-associated virus vectors efficiently and persistently transduce chondrocytes in normal and osteoarthritic human articular cartilage. Hum Gene Ther 14:393–402

    Google Scholar 

  84. Hirschmann F, Verhoeyen E, Wirth D, Bauwens S, Hauser H, Rudert M (2002) Vital marking of articular chondrocytes by retroviral infection using green fluorescence protein. Osteoarthritis Cartilage 10:109–118

    Google Scholar 

  85. Shakibaei M, Seifarth C, John T, Rahmanzadeh M, 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

    Google Scholar 

  86. Sung L-Y, Chiu H-Y, Chen H-C, Chen Y-L, Chuang C-K, Hu Y-C (2009) Baculovirus-mediated growth factor expression in dedifferentiated chondrocytes accelerates redifferentiation: effects of combinational transduction. Tissue Eng Part A 15:1353–1362

    Google Scholar 

  87. Nesic D, Whiteside R, Brittberg M, Wendt D, Martin I, Mainil-Varlet P (2006) Cartilage tissue engineering for degenerative joint disease. Adv Drug Deliv Rev 58:300–322

    Google Scholar 

  88. Chen H-C, Sung L-Y, Lo W-H, Chuang C-K, Wang Y-H, Lin J-L et al (2008) Combination of baculovirus-mediated BMP-2 expression and rotating-shaft bioreactor culture synergistically enhances cartilage formation. Gene Ther 15:309–317

    Google Scholar 

  89. Saini S, Wick TM (2003) Concentric cylinder bioreactor for production of tissue engineered cartilage: effect of seeding density and hydrodynamic loading on construct development. Biotechnol Prog 19:510–521

    Google Scholar 

  90. Bueno EM, Bilgen B, Barabino GA (2005) Wavy-walled bioreactor supports increased cell proliferation and matrix deposition in engineered cartilage constructs. Tissue Eng 11:1699–1709

    Google Scholar 

  91. Carver SE, Heath CA (1999) Increasing extracellular matrix production in regenerating cartilage with intermittent physiological pressure. Biotechnol Bioeng 62:166–174

    Google Scholar 

  92. Freed LE, Langer R, Martin I, Pellis NR, VunjakNovakovic G (1997) Tissue engineering of cartilage in space. Proc Natl Acad Sci U S A 94:13885–13890

    Google Scholar 

  93. Hoch DH, Grodzinsky AJ, Koob TJ, Albert ML, Eyre DR (1983) Early changes in material properties of rabbit articular cartilage after meniscectomy. J Orthop Res 1:4–12

    Google Scholar 

  94. Madry H, Cucchiarini M, Stein U, Remberger K, Kohn D, Trippel SB (2003) 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 5:502–509

    Google Scholar 

  95. Zachos TA, Diggs A, Weisbrode S, Bartlett J, Bertone AL (2007) Mesenchymal stem cell-mediated gene delivery of bone morphogenetic protein-2 in an articular fracture model. Mol Ther 15:1543–1550

    Google Scholar 

  96. Hanada K, Solchaga LA, Caplan AI, Hering TM, Goldberg VM, Yoo JU et al (2001) BMP-2 induction and TGF-β1 modulation of rat periosteal cell chondrogenesis. J Cell Biochem 81:284–294

    Google Scholar 

  97. Caplan AI, Bruder SP (2001) Mesenchymal stem cells: building blocks for molecular medicine in the 21st century. Trends Mol Med 7:259–264

    Google Scholar 

  98. Bruder SP, Jaiswal N, Haynesworth SE (1997) Growth kinetics, self-renewal, and the osteogenic potential of purified human mesenchymal stem cells during extensive subcultivation and following cryopreservation. J Cell Biochem 64:278–294

    Google Scholar 

  99. Carlberg AL, Pucci B, Rallapalli R, Tuan RS, Hall DJ (2001) Efficient chondrogenic differentiation of mesenchymal cells in micromass culture by retroviral gene transfer of BMP-2. Differentiation 67:128–138

    Google Scholar 

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

    Google Scholar 

  101. Caplan AI, Elyaderani M, Mochizuki Y, Wakitani S, Goldberg VM (1997) Principles of cartilage repair and regeneration. Clin Orthop 342:254–269

    Google Scholar 

  102. Pelttari K, Winter A, Steck E, Goetzke K, Hennig T, Ochs BG et al (2006) Premature induction of hypertrophy during in vitro chondrogenesis of human mesenchymal stem cells correlates with calcification and vascular invasion after ectopic transplantation in SCID mice. Arthritis Rheum 54:3254–3266

    Google Scholar 

  103. Wang W, Li B, Li Y, Jiang Y, Ouyang H, Gao C (2010) In vivo restoration of full-thickness cartilage defects by poly(lactide-co-glycolide) sponges filled with fibrin gel, bone marrow mesenchymal stem cells and DNA complexes. Biomaterials 31:5953–5965

    Google Scholar 

  104. Marx JC, Allay JA, Persons DA, Nooner SA, Hargrove PW, Kelly PF et al (1999) High-efficiency transduction and long-term gene expression with a murine stem cell retroviral vector encoding the green fluorescent protein in human marrow stromal cells. Hum Gene Ther 10:1163–1173

    Google Scholar 

  105. Gazit D, Turgeman G, Kelley P, Wang E, Jalenak M, Zilberman Y et al (1999) Engineered pluripotent mesenchymal cells integrate and differentiate in regenerating bone: a novel cell-mediated gene therapy. J Gene Med 1:121–133

    Google Scholar 

  106. Martinek V, Fu FH, Lee CW, Huard J (2001) Treatment of osteochondral injuries – genetic engineering. Clin Sports Med 20:403–416, viii

    Google Scholar 

  107. Ho Y-C, Chung Y-C, Hwang S-M, Wang K-C, Hu Y-C (2005) Transgene expression and differentiation of baculovirus-transduced human mesenchymal stem cells. J Gene Med 7:860–868

    Google Scholar 

  108. Ho Y-C, Lee H-P, Hwang S-M, Lo W-H, Chen H-C, Chung C-K et al (2006) Baculovirus transduction of human mesenchymal stem cell-derived progenitor cells: variation of transgene expression with cellular differentiation states. Gene Ther 13:1471–1479

    Google Scholar 

  109. Palmer GD, Steinert A, Pascher A, Gouze E, Gouze JN, Betz O et al (2005) Gene-induced chondrogenesis of primary mesenchymal stem cells in vitro. Mol Ther 12:219–228

    Google Scholar 

  110. Steinert AF, Palmer GD, Pilapil C, Nöth U, Evans CH, Ghivizzani SC (2008) Enhanced in vitro chondrogenesis of primary mesenchymal stem cells by combined gene transfer. Tissue Eng Part A 15:1127–1139

    Google Scholar 

  111. Kim HJ, Im GI (2011) Electroporation-mediated transfer of SOX trio genes (SOX-5, SOX-6, and SOX-9) to enhance the chondrogenesis of mesenchymal stem cells. Stem Cells Dev 20:2103–2114

    MathSciNet  Google Scholar 

  112. Park JS, Yang HN, Woo DG, Jeon SY, Do HJ, Lim HY et al (2011) Chondrogenesis of human mesenchymal stem cells mediated by the combination of SOX trio SOX5, 6, and 9 genes complexed with PEI-modified PLGA nanoparticles. Biomaterials 32:3679–3688

    Google Scholar 

  113. Mahmoudifar N, Doran PM (2010) Chondrogenic differentiation of human adipose-derived stem cells in polyglycolic acid mesh scaffolds under dynamic culture conditions. Biomaterials 31:3858–3867

    Google Scholar 

  114. Santo VE, Gomes ME, Mano JF, Reis RL (2013) Controlled release strategies for bone, cartilage, and osteochondral engineering-Part II: challenges on the evolution from single to multiple bioactive factor delivery. Tissue Eng Part B Rev 19:327–352

    Google Scholar 

  115. Freyria A-M, Mallein-Gerin F (2012) Chondrocytes or adult stem cells for cartilage repair: the indisputable role of growth factors. Injury 43:259–265

    Google Scholar 

  116. Diekman BO, Estes BT, Guilak F (2010) The effects of BMP6 overexpression on adipose stem cell chondrogenesis: interactions with dexamethasone and exogenous growth factors. J Biomed Mater Res A 93:994–1003

    Google Scholar 

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

    Google Scholar 

  118. Sophia Fox AJ, Bedi A, Rodeo SA (2009) The basic science of articular cartilage: structure, composition, and function. Sports Health 1:461–468

    Google Scholar 

  119. Keeney M, Lai JH, Yang F (2011) Recent progress in cartilage tissue engineering. Curr Opin Biotechnol 25:734–740

    Google Scholar 

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

    Google Scholar 

  121. Yang HN, Park JS, Woo DG, Jeon SY, Do HJ, Lim HY et al (2011) Chondrogenesis of mesenchymal stem cells and dedifferentiated chondrocytes by transfection with SOX Trio genes. Biomaterials 32:7695–7704

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

Copyright information

© 2014 The Author(s)

About this chapter

Cite this chapter

Hu, YC. (2014). Gene Therapy for Cartilage Tissue Engineering. In: Gene Therapy for Cartilage and Bone Tissue Engineering. SpringerBriefs in Bioengineering. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-53923-7_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-53923-7_4

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-53922-0

  • Online ISBN: 978-3-642-53923-7

  • eBook Packages: EngineeringEngineering (R0)

Publish with us

Policies and ethics