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Published in: Archives of Dermatological Research 1/2017

01-01-2017 | Original Paper

3D modeling of keloid scars in vitro by cell and tissue engineering

Authors: Dutsadee Suttho, Samlee Mankhetkorn, Delphine Binda, Lionel Pazart, Philippe Humbert, Gwenaël Rolin

Published in: Archives of Dermatological Research | Issue 1/2017

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Abstract

Keloids are pathologic scars defined as dermal fibrotic tumors resulting from a disturbance of skin wound healing process. Treatments against keloids are multiple, sometimes empirical and none of them really provides an effective tool for physicians. The lack of effective treatments is correlated with the poor understanding of keloid pathogenesis. To fill this gap, researchers need strong models mimicking keloids as closely as possible. The objective of this study was to establish in vitro a new reconstructed keloid model (RKM), by combining fibroblasts extracted from the three major area of a keloid (center, periphery, non-lesional) in a three-dimensional biomaterial. To this aim, fibroblasts of three keloid locations were extracted and characterized, and then integrated in a hydrated collagen gel matrix during a three-step procedure. The heterogeneity of fibroblasts was assessed according to their proliferative and remodeling capacities. RKMs were further visualized and characterized by both light and scanning electron microscopy. This reconstructed keloid model should be very useful for investigating keloid fibroblasts function in conditions mimicking in vivo situation. Moreover, RKM should also be a suitable model for either drug study and discovery or innovative approaches using medical devices both during cancer and cancer-like disease investigation.
Literature
1.
go back to reference Agha R, Ogawa R, Pietramaggiori G, Orgill DP (2011) A review of the role of mechanical forces in cutaneous wound healing. J Surg Res 171:700–708CrossRefPubMed Agha R, Ogawa R, Pietramaggiori G, Orgill DP (2011) A review of the role of mechanical forces in cutaneous wound healing. J Surg Res 171:700–708CrossRefPubMed
2.
go back to reference Atiyeh BS, Costagliola M, Hayek SN (2005) Keloid or hypertrophic scar: the controversy: review of the literature. Ann Plast Surg 54:676–680CrossRefPubMed Atiyeh BS, Costagliola M, Hayek SN (2005) Keloid or hypertrophic scar: the controversy: review of the literature. Ann Plast Surg 54:676–680CrossRefPubMed
4.
go back to reference Bell E, Ivarsson B, Merrill C (1979) Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative potential in vitro. Proc Natl Acad Sci 76:1274–1278CrossRefPubMedPubMedCentral Bell E, Ivarsson B, Merrill C (1979) Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative potential in vitro. Proc Natl Acad Sci 76:1274–1278CrossRefPubMedPubMedCentral
5.
go back to reference Brown RA (2013) In the beginning there were soft collagen cell gels: towards better 3D connective tissue models? Exp Cell Res 319:2460–2469CrossRefPubMed Brown RA (2013) In the beginning there were soft collagen cell gels: towards better 3D connective tissue models? Exp Cell Res 319:2460–2469CrossRefPubMed
6.
go back to reference Butler PD, Longaker MT, Yang GP (2008) Current progress in keloid research and treatment. J Am Coll Surg 206:731–741CrossRefPubMed Butler PD, Longaker MT, Yang GP (2008) Current progress in keloid research and treatment. J Am Coll Surg 206:731–741CrossRefPubMed
8.
go back to reference Chipev CC, Simman R, Hatch G, Katz AE, Siegel DM, Simon M (2000) Myofibroblast phenotype and apoptosis in keloid and palmar fibroblasts in vitro. Cell Death Differ 7:166–176CrossRefPubMed Chipev CC, Simman R, Hatch G, Katz AE, Siegel DM, Simon M (2000) Myofibroblast phenotype and apoptosis in keloid and palmar fibroblasts in vitro. Cell Death Differ 7:166–176CrossRefPubMed
9.
go back to reference Ehrlich HP, Needle AL (1983) Wound healing in tight-skin mice: delayed closure of excised wounds. Plast Reconstr Surg 72:190–198CrossRefPubMed Ehrlich HP, Needle AL (1983) Wound healing in tight-skin mice: delayed closure of excised wounds. Plast Reconstr Surg 72:190–198CrossRefPubMed
10.
go back to reference Ehrlich HP, Moyer KE (2013) Cell-populated collagen lattice contraction model for the investigation of fibroblast collagen interactions. Methods Mol Biol 1037:45–58CrossRefPubMed Ehrlich HP, Moyer KE (2013) Cell-populated collagen lattice contraction model for the investigation of fibroblast collagen interactions. Methods Mol Biol 1037:45–58CrossRefPubMed
11.
go back to reference Hasegawa T, Nakao A, Sumiyoshi K, Tsuchihashi H, Ogawa H (2005) SB-431542 inhibits TGF-beta-induced contraction of collagen gel by normal and keloid fibroblasts. J Dermatol Sci 39:33–38CrossRefPubMed Hasegawa T, Nakao A, Sumiyoshi K, Tsuchihashi H, Ogawa H (2005) SB-431542 inhibits TGF-beta-induced contraction of collagen gel by normal and keloid fibroblasts. J Dermatol Sci 39:33–38CrossRefPubMed
12.
go back to reference Jain P, Worthylake R, Alahari S (2012) Quantitative analysis of random migration of cells using time-lapse video microscopy. J Vis Exp 13:e3585 Jain P, Worthylake R, Alahari S (2012) Quantitative analysis of random migration of cells using time-lapse video microscopy. J Vis Exp 13:e3585
13.
go back to reference Janson DG, Saintigny G, van Adrichem A, Mahé C, El Ghalbzouri A (2012) Different gene expression patterns in human papillary and reticular fibroblasts. J Investig Dermatol 132:2565–2572CrossRefPubMed Janson DG, Saintigny G, van Adrichem A, Mahé C, El Ghalbzouri A (2012) Different gene expression patterns in human papillary and reticular fibroblasts. J Investig Dermatol 132:2565–2572CrossRefPubMed
14.
go back to reference Janson D, Saintigny G, Mahé C, El Ghalbzouri A (2013) Papillary fibroblasts differentiate into reticular fibroblasts after prolonged in vitro culture. Exp Dermatol 22:48–53CrossRefPubMed Janson D, Saintigny G, Mahé C, El Ghalbzouri A (2013) Papillary fibroblasts differentiate into reticular fibroblasts after prolonged in vitro culture. Exp Dermatol 22:48–53CrossRefPubMed
15.
go back to reference Kamamoto F, Paggiaro AO, Rodas A, Herson MR, Mathor MB, Ferreira MC (2003) A wound contraction experimental model for studying keloids and wound-healing modulators. Artif Organs 27:701–705CrossRefPubMed Kamamoto F, Paggiaro AO, Rodas A, Herson MR, Mathor MB, Ferreira MC (2003) A wound contraction experimental model for studying keloids and wound-healing modulators. Artif Organs 27:701–705CrossRefPubMed
16.
go back to reference Kischer CW, Pindur J, Shetlar MR, Shetlar CL (1989) Implants of hypertrophic scars and keloids into the nude (athymic) mouse: viability and morphology. J Trauma 29:672–677CrossRefPubMed Kischer CW, Pindur J, Shetlar MR, Shetlar CL (1989) Implants of hypertrophic scars and keloids into the nude (athymic) mouse: viability and morphology. J Trauma 29:672–677CrossRefPubMed
17.
go back to reference Lee WJ, Choi I-K, Lee JH, Kim YO, Yun C-O (2013) A novel three-dimensional model system for keloid study: organotypic multicellular scar model. Wound Repair Regen 21:155–165CrossRefPubMed Lee WJ, Choi I-K, Lee JH, Kim YO, Yun C-O (2013) A novel three-dimensional model system for keloid study: organotypic multicellular scar model. Wound Repair Regen 21:155–165CrossRefPubMed
18.
go back to reference Li H, Nahas Z, Feng F, Elisseeff JH, Boahene K (2013) Tissue engineering for in vitro analysis of matrix metalloproteinases in the pathogenesis of keloid lesions. JAMA Facial Plast Surg 15:448–456CrossRefPubMed Li H, Nahas Z, Feng F, Elisseeff JH, Boahene K (2013) Tissue engineering for in vitro analysis of matrix metalloproteinases in the pathogenesis of keloid lesions. JAMA Facial Plast Surg 15:448–456CrossRefPubMed
19.
go back to reference Ma H, Zhao X, Chen G, Fang R, Zhang F (2016) Silencing NLRC5 inhibits extracellular matrix expression in keloid fibroblasts via inhibition of transforming growth factor-β1/Smad signaling pathway. Biomed Pharmacother 83:1016–1021CrossRefPubMed Ma H, Zhao X, Chen G, Fang R, Zhang F (2016) Silencing NLRC5 inhibits extracellular matrix expression in keloid fibroblasts via inhibition of transforming growth factor-β1/Smad signaling pathway. Biomed Pharmacother 83:1016–1021CrossRefPubMed
20.
go back to reference Morris DE, Wu L, Zhao LL et al (1997) Acute and chronic animal models for excessive dermal scarring: quantitative studies. Plast Reconstr Surg 100:674–681CrossRefPubMed Morris DE, Wu L, Zhao LL et al (1997) Acute and chronic animal models for excessive dermal scarring: quantitative studies. Plast Reconstr Surg 100:674–681CrossRefPubMed
21.
go back to reference Phan TT, Lim IJ, Bay BH et al (2002) Differences in collagen production between normal and keloid-derived fibroblasts in serum-media co-culture with keloid-derived keratinocytes. J Dermatol Sci 29:26–34CrossRefPubMed Phan TT, Lim IJ, Bay BH et al (2002) Differences in collagen production between normal and keloid-derived fibroblasts in serum-media co-culture with keloid-derived keratinocytes. J Dermatol Sci 29:26–34CrossRefPubMed
22.
go back to reference Philandrianos C, Gonnelli D, Andrac-Meyer L, Bruno M, Magalon G, Mordon S (2014) Establishment of a keloid model by transplanting human keloid onto the backs of nude mice. Ann Chir Plast Esthet 59:246–252CrossRefPubMed Philandrianos C, Gonnelli D, Andrac-Meyer L, Bruno M, Magalon G, Mordon S (2014) Establishment of a keloid model by transplanting human keloid onto the backs of nude mice. Ann Chir Plast Esthet 59:246–252CrossRefPubMed
23.
go back to reference Ridley A, Schwartz M, Burridge K et al (2003) Cell migration: integrating signals from front to back. Science 302:1704–1709CrossRefPubMed Ridley A, Schwartz M, Burridge K et al (2003) Cell migration: integrating signals from front to back. Science 302:1704–1709CrossRefPubMed
24.
go back to reference Rolin G, Placet V, Jacquet E et al (2012) Development and characterization of a human dermal equivalent with physiological mechanical properties. Skin Res Technol 18:251–258CrossRefPubMed Rolin G, Placet V, Jacquet E et al (2012) Development and characterization of a human dermal equivalent with physiological mechanical properties. Skin Res Technol 18:251–258CrossRefPubMed
25.
go back to reference Saito M, Yamazaki M, Maeda T, Matsumura H, Setoguchi Y, Tsuboi R (2012) Pirfenidone suppresses keloid fibroblast-embedded collagen gel contraction. Arch Dermatol Res 304:217–222CrossRefPubMed Saito M, Yamazaki M, Maeda T, Matsumura H, Setoguchi Y, Tsuboi R (2012) Pirfenidone suppresses keloid fibroblast-embedded collagen gel contraction. Arch Dermatol Res 304:217–222CrossRefPubMed
26.
go back to reference Sarrazy V, Billet F, Micallef L, Coulomb B, Desmoulière A (2011) Mechanisms of pathological scarring: role of myofibroblasts and current developments. Wound Repair Regen 19(Suppl 1):s10–s15CrossRefPubMed Sarrazy V, Billet F, Micallef L, Coulomb B, Desmoulière A (2011) Mechanisms of pathological scarring: role of myofibroblasts and current developments. Wound Repair Regen 19(Suppl 1):s10–s15CrossRefPubMed
27.
go back to reference Satish L, Lyons-Weiler J, Hebda PA, Wells A (2006) Gene expression patterns in isolated keloid fibroblasts. Wound Repair Regen 14:463–470CrossRefPubMed Satish L, Lyons-Weiler J, Hebda PA, Wells A (2006) Gene expression patterns in isolated keloid fibroblasts. Wound Repair Regen 14:463–470CrossRefPubMed
28.
go back to reference Sayah DN, Soo C, Shaw WW et al (1999) Downregulation of apoptosis-related genes in keloid tissues. J Surg Res 87:209–216CrossRefPubMed Sayah DN, Soo C, Shaw WW et al (1999) Downregulation of apoptosis-related genes in keloid tissues. J Surg Res 87:209–216CrossRefPubMed
29.
go back to reference Seo BF, Lee JY, Jung SN (2013) Models of abnormal scarring. Bio Med Res Int 2013:423147 Seo BF, Lee JY, Jung SN (2013) Models of abnormal scarring. Bio Med Res Int 2013:423147
30.
go back to reference Shetlar MR, Shetlar CL, Kischer CW, Pindur J (1991) Implants of keloid and hypertrophic scars into the athymic nude mouse: changes in the glycosaminoglycans of the implants. Connect Tissue Res 26:23–36CrossRefPubMed Shetlar MR, Shetlar CL, Kischer CW, Pindur J (1991) Implants of keloid and hypertrophic scars into the athymic nude mouse: changes in the glycosaminoglycans of the implants. Connect Tissue Res 26:23–36CrossRefPubMed
31.
go back to reference Shih B, Garside E, McGrouther DA, Bayat A (2010) Molecular dissection of abnormal wound healing processes resulting in keloid disease. Wound Repair Regen 18:139–153CrossRefPubMed Shih B, Garside E, McGrouther DA, Bayat A (2010) Molecular dissection of abnormal wound healing processes resulting in keloid disease. Wound Repair Regen 18:139–153CrossRefPubMed
32.
go back to reference Syed F, Ahmadi E, Iqbal SA, Singh S, McGrouther DA, Bayat A (2011) Fibroblasts from the growing margin of keloid scars produce higher levels of collagen I and III compared with intralesional and extralesional sites: clinical implications for lesional site-directed therapy. Br J Dermatol 164:83–96CrossRefPubMed Syed F, Ahmadi E, Iqbal SA, Singh S, McGrouther DA, Bayat A (2011) Fibroblasts from the growing margin of keloid scars produce higher levels of collagen I and III compared with intralesional and extralesional sites: clinical implications for lesional site-directed therapy. Br J Dermatol 164:83–96CrossRefPubMed
33.
go back to reference Tucci-Viegas VM, Hochman B, França JP, Ferreira LM (2010) Keloid explant culture: a model for keloid fibroblasts isolation and cultivation based on the biological differences of its specific regions. Int Wound J 7:339–348CrossRefPubMed Tucci-Viegas VM, Hochman B, França JP, Ferreira LM (2010) Keloid explant culture: a model for keloid fibroblasts isolation and cultivation based on the biological differences of its specific regions. Int Wound J 7:339–348CrossRefPubMed
34.
go back to reference Tan EM, Hoffren J, Rouda S et al (1993) Decorin, versican, and biglycan gene expression by keloid and normal dermal fibroblasts: differential regulation by basic fibroblast growth factor. Exp Cell Res 209:200–207CrossRefPubMed Tan EM, Hoffren J, Rouda S et al (1993) Decorin, versican, and biglycan gene expression by keloid and normal dermal fibroblasts: differential regulation by basic fibroblast growth factor. Exp Cell Res 209:200–207CrossRefPubMed
35.
go back to reference Ud-Din S, Bayat A (2013) Strategic management of keloid disease in ethnic skin: a structured approach supported by the emerging literature. Br J Dermatol 169(Suppl 3):71–81CrossRefPubMed Ud-Din S, Bayat A (2013) Strategic management of keloid disease in ethnic skin: a structured approach supported by the emerging literature. Br J Dermatol 169(Suppl 3):71–81CrossRefPubMed
36.
go back to reference Uitto J, Perejda AJ, Abergel RP, Chu ML, Ramirez F (1985) Altered steady-state ratio of type I/III procollagen mRNAs correlates with selectively increased type I procollagen biosynthesis in cultured keloid fibroblasts. Proc Natl Acad Sci 82:5935–5939CrossRefPubMedPubMedCentral Uitto J, Perejda AJ, Abergel RP, Chu ML, Ramirez F (1985) Altered steady-state ratio of type I/III procollagen mRNAs correlates with selectively increased type I procollagen biosynthesis in cultured keloid fibroblasts. Proc Natl Acad Sci 82:5935–5939CrossRefPubMedPubMedCentral
37.
go back to reference Williams FN, Herndon DN, Branski LK (2014) Where we stand with human hypertrophic and keloid scar models. Exp Dermatol 23:811–812CrossRefPubMed Williams FN, Herndon DN, Branski LK (2014) Where we stand with human hypertrophic and keloid scar models. Exp Dermatol 23:811–812CrossRefPubMed
38.
39.
go back to reference Zhang J, Liu C, Wan Y, Peng L, Li W, Qiu J (2016) Long non-coding RNA H19 promotes the proliferation of fibroblasts in keloid scarring. Oncol Lett 12:2835–2839PubMedPubMedCentral Zhang J, Liu C, Wan Y, Peng L, Li W, Qiu J (2016) Long non-coding RNA H19 promotes the proliferation of fibroblasts in keloid scarring. Oncol Lett 12:2835–2839PubMedPubMedCentral
40.
go back to reference Zhu KQ, Engrav LH, Gibran NS et al (2003) The female, red Duroc pig as an animal model of hypertrophic scarring and the potential role of the cones of skin. Burns 29:649–664CrossRefPubMed Zhu KQ, Engrav LH, Gibran NS et al (2003) The female, red Duroc pig as an animal model of hypertrophic scarring and the potential role of the cones of skin. Burns 29:649–664CrossRefPubMed
Metadata
Title
3D modeling of keloid scars in vitro by cell and tissue engineering
Authors
Dutsadee Suttho
Samlee Mankhetkorn
Delphine Binda
Lionel Pazart
Philippe Humbert
Gwenaël Rolin
Publication date
01-01-2017
Publisher
Springer Berlin Heidelberg
Published in
Archives of Dermatological Research / Issue 1/2017
Print ISSN: 0340-3696
Electronic ISSN: 1432-069X
DOI
https://doi.org/10.1007/s00403-016-1703-2

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