The American Journal of Surgery
Volume 195, Issue 2 , Pages 144-148 , February 2008

Use of organotypic coculture to study keloid biology

Presented at the 17th Annual Scientific Session of the Society for Black Academic Surgeons, Chicago, IL, April 12–15, 2007

  • Paris D. Butler, M.D.

      Affiliations

    • Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA
    • Department of Surgery, University of Virginia School of Medicine, Charlottesville, VA, USA
  • ,
  • Daphne P. Ly, M.D.

      Affiliations

    • Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA
  • ,
  • Michael T. Longaker, M.D., M.B.A., F.A.C.S.

      Affiliations

    • Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA
  • ,
  • George P. Yang, M.D., Ph.D., F.A.C.S.

      Affiliations

    • Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA
    • Palo Alto Veterans Administration Health Care System, Palo Alto, CA, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1-650-725-5644; fax: +1-650-736-1705.

Received 8 June 2007 ,Revised 15 October 2007

References 

  1. Russell SB, Trupin KM, Rodriguez-Eaton S, et al. Reduced growth-factor requirement of keloid-derived fibroblasts may account for tumor growth. Proc Natl Acad Sci U S A. 1988;85(2):587–591
  2. Atiyeh BS, Costagliola M, Hayek SN. Keloid or hypertrophic scar: the controversy: review of the literature. Ann Plast Surg. 2005;54(6):676–680
  3. Nirodi CS, Devalaraja R, Nanney LB, et al. Chemokine and chemokine receptor expression in keloid and normal fibroblasts. Wound Repair Regen. 2000;8(5):371–382
  4. De Felice B, Wilson RR, Nacca M, et al. Molecular characterization and expression of p63 isoforms in human keloids. Mol Genet Genomics. 2004;272(1):28–34
  5. Kiil J. Keloids treated with topical injections of triamcinolone acetonide (kenalog) (Immediate and long-term results). Scand J Plast Reconstr Surg. 1977;11(2):169–172
  6. Davison SP, Mess S, Kauffman LC, et al. Ineffective treatment of keloids with interferon alpha-2b. Plast Reconstr Surg. 2006;117(1):247–252
  7. Ragoowansi R, Cornes PG, Moss AL, et al. Treatment of keloids by surgical excision and immediate postoperative single-fraction radiotherapy. Plast Reconstr Surg. 2003;111(6):1853–1859
  8. Meythiaz A, de Mey A, Lejour M. Treatment of keloids by excision and postoperative radiotherapy. Eur J Plast Surg. 1992;15:13–16
  9. Mustoe TA, Cooter RD, Gold MH, et al. International clinical recommendations on scar management. Plast Reconstr Surg. 2002;110(2):560–571
  10. Niessen FB, Spauwen PH, Schalkwijk J, et al. On the nature of hypertrophic scars and keloids: a review. Plast Reconstr Surg. 1999;104(5):1435–1458
  11. Slemp AE, Kirschner RE. Keloids and scars: a review of keloids and scars, their pathogenesis, risk factors, and management. Curr Opin Pediatr. 2006;18(4):396–402
  12. Berman B, Bieley HC. Adjunct therapies to surgical management of keloids. Dermatol Surg. 1996;22(2):126–130
  13. Sandulache VC, Parekh A, Li-Korotky H, et al. Prostaglandin E2 inhibition of keloid fibroblast migration, contraction, and transforming growth factor (TGF)-beta1-induced collagen synthesis. Wound Repair Regen. 2007;15(1):122–133
  14. Xia W, Longaker MT, Yang GP. P38 MAP kinase mediates transforming growth factor-beta2 transcription in human keloid fibroblasts. Am J Physiol Regul Integr Comp Physiol. 2006;290(3):R501–R508
  15. Chin GS, Liu W, Peled Z, et al. Differential expression of transforming growth factor-beta receptors I and II and activation of Smad 3 in keloid fibroblasts. Plast Reconstr Surg. 2001;108(2):423–429
  16. Haisa M, Okochi H, Grotendorst GR. Elevated levels of PDGF alpha receptors in keloid fibroblasts contribute to an enhanced response to PDGF. J Invest Dermatol. 1994;103(4):560–563
  17. Xia X KW, Phan TT, Lim IJ, et al. Increased CCN2 transcription in keloid fibroblasts requires cooperativity between AP-1 and Smad binding sites. Ann Surg. 2007;246(5):886–895
  18. Ikuta S, Sekino N, Hara T, et al. Mouse epidermal keratinocytes in three-dimensional organotypic coculture with dermal fibroblasts form a stratified sheet resembling skin. Biosci Biotechnol Biochem. 2006;70(11):2669–2675
  19. Maas-Szabowski N, Stark HJ, Fusenig NE. Keratinocyte growth regulation in defined organotypic cultures through IL-1-induced keratinocyte growth factor expression in resting fibroblasts. J Invest Dermatol. 2000;114(6):1075–1084
  20. Maas-Szabowski N, Szabowski A, Stark HJ, et al. Organotypic cocultures with genetically modified mouse fibroblasts as a tool to dissect molecular mechanisms regulating keratinocyte growth and differentiation. J Invest Dermatol. 2001;116(5):816–820
  21. Stark HJ, Szabowski A, Fusenig NE, et al. Organotypic cocultures as skin equivalents: a complex and sophisticated in vitro system. Biol Proceed Online. 2004;6:55–60
  22. Maas-Szabowski N, Fusenig NE, Stark HJ. Experimental models to analyze differentiation functions of cultured keratinocytes in vitro and in vivo. Methods Mol Biol. 2005;289:47–60
  23. Paul Ehrlich H, Sun B, Kainth KS, et al. Elucidating the mechanism of wound contraction: rapid versus sustained myosin ATPase activity in attached-delayed-released compared with free-floating fibroblast-populated collagen lattices. Wound Repair Regen. 2006;14(5):625–632
  24. Grinnell F. Fibroblasts, myofibroblasts, and wound contraction. J Cell Biol. 1994;124(4):401–404
  25. Berry DP, Harding KG, Stanton MR, et al. Human wound contraction: collagen organization, fibroblasts, and myofibroblasts. Plast Reconstr Surg. 1998;102(1):124–134
  26. Sewall GK, Robertson KM, Connor NP, et al. Effect of topical mitomycin on skin wound contraction. Arch Facial Plast Surg. 2003;5(1):59–62
  27. Moulin V, Castilloux G, Jean A, et al. In vitro models to study wound healing fibroblasts. Burns. 1996;22(5):359–362
  28. Campaner AB, Ferreira LM, Gragnani A, et al. Upregulation of TGF-beta1 expression may be necessary but is not sufficient for excessive scarring. J Invest Dermatol. 2006;126(5):1168–1176
  29. Chipev CC, Simon M. Phenotypic differences between dermal fibroblasts from different body sites determine their responses to tension and TGFbeta1. BMC Dermatol. 2002;2:13
  30. Lim IJ, Phan TT, Song C, et al. Investigation of the influence of keloid-derived keratinocytes on fibroblast growth and proliferation in vitro. Plast Reconstr Surg. 2001;107(3):797–808
  31. Xia W, Phan TT, Lim IJ, et al. Complex epithelial-mesenchymal interactions modulate transforming growth factor-beta expression in keloid-derived cells. Wound Repair Regen. 2004;12(5):546–556

PII: S0002-9610(07)00874-4

doi: 10.1016/j.amjsurg.2007.10.003

The American Journal of Surgery
Volume 195, Issue 2 , Pages 144-148 , February 2008