Characterization of In Vitro Reconstructed Human Normotrophic, Hypertrophic, and Keloid Scar Models. 2018

Grace C Limandjaja, and Lenie J van den Broek, and Melanie Breetveld, and Taco Waaijman, and Stan Monstrey, and Edith M de Boer, and Rik J Scheper, and Frank B Niessen, and Susan Gibbs
1 Department of Dermatology, VU Medical Centre (VUMC) , Amsterdam, The Netherlands .

To understand scar pathology, develop new drugs, and provide a platform for personalized medicine, physiologically relevant human scar models are required, which are characteristic of different scar pathologies. Hypertrophic scars and keloids are two types of abnormal scar resulting from unknown abnormalities in the wound healing process. While they display different clinical behavior, differentiation between the two can be difficult-which in turn means that it is difficult to develop optimal therapeutic strategies. The aim of this study was to develop in vitro reconstructed human hypertrophic and keloid scar models and compare these to normotrophic scar and normal skin models to identify distinguishing biomarkers. Keratinocytes and fibroblasts from normal skin and scar types (normotrophic, hypertrophic, keloid) were used to reconstruct skin models. All skin models showed a reconstructed differentiated epidermis on a fibroblast populated collagen-elastin matrix. Both abnormal scar types showed increased contraction, dermal thickness, and myofibroblast staining compared to normal skin and normotrophic scar. Notably, the expression of extracellular matrix associated genes showed distinguishing profiles between all scar types and normal skin (hyaluronan synthase-1, matrix-metalloprotease-3), between keloid and normal skin (collagen type IV), between normal scar and keloid (laminin α1), and between keloid and hypertrophic scar (matrix-metalloprotease-1, integrin α5). Also, inflammatory cytokine and growth factor secretion (CCL5, CXCL1, CXCL8, CCL27, IL-6, HGF) showed differential secretion between scar types. Our results strongly suggest that abnormal scars arise from different pathologies rather than simply being on different ends of the scarring spectrum. Furthermore, such normal skin and scar models together with biomarkers, which distinguish the different scar types, would provide an animal free, physiologically relevant scar diagnostic and drug testing platform for the future.

UI MeSH Term Description Entries
D007223 Infant A child between 1 and 23 months of age. Infants
D007627 Keloid A sharply elevated, irregularly shaped, progressively enlarging scar resulting from formation of excessive amounts of collagen in the dermis during connective tissue repair. It is differentiated from a hypertrophic scar (CICATRIX, HYPERTROPHIC) in that the former does not spread to surrounding tissues. Keloids
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D002648 Child A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL. Children
D002675 Child, Preschool A child between the ages of 2 and 5. Children, Preschool,Preschool Child,Preschool Children
D005260 Female Females

Related Publications

Grace C Limandjaja, and Lenie J van den Broek, and Melanie Breetveld, and Taco Waaijman, and Stan Monstrey, and Edith M de Boer, and Rik J Scheper, and Frank B Niessen, and Susan Gibbs
January 2009, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society,
Grace C Limandjaja, and Lenie J van den Broek, and Melanie Breetveld, and Taco Waaijman, and Stan Monstrey, and Edith M de Boer, and Rik J Scheper, and Frank B Niessen, and Susan Gibbs
November 2014, Experimental dermatology,
Grace C Limandjaja, and Lenie J van den Broek, and Melanie Breetveld, and Taco Waaijman, and Stan Monstrey, and Edith M de Boer, and Rik J Scheper, and Frank B Niessen, and Susan Gibbs
August 2015, Experimental dermatology,
Grace C Limandjaja, and Lenie J van den Broek, and Melanie Breetveld, and Taco Waaijman, and Stan Monstrey, and Edith M de Boer, and Rik J Scheper, and Frank B Niessen, and Susan Gibbs
August 1991, Plastic and reconstructive surgery,
Grace C Limandjaja, and Lenie J van den Broek, and Melanie Breetveld, and Taco Waaijman, and Stan Monstrey, and Edith M de Boer, and Rik J Scheper, and Frank B Niessen, and Susan Gibbs
April 2005, Annales de dermatologie et de venereologie,
Grace C Limandjaja, and Lenie J van den Broek, and Melanie Breetveld, and Taco Waaijman, and Stan Monstrey, and Edith M de Boer, and Rik J Scheper, and Frank B Niessen, and Susan Gibbs
January 1995, Duodecim; laaketieteellinen aikakauskirja,
Grace C Limandjaja, and Lenie J van den Broek, and Melanie Breetveld, and Taco Waaijman, and Stan Monstrey, and Edith M de Boer, and Rik J Scheper, and Frank B Niessen, and Susan Gibbs
January 1971, Surgical forum,
Grace C Limandjaja, and Lenie J van den Broek, and Melanie Breetveld, and Taco Waaijman, and Stan Monstrey, and Edith M de Boer, and Rik J Scheper, and Frank B Niessen, and Susan Gibbs
January 1996, Duodecim; laaketieteellinen aikakauskirja,
Grace C Limandjaja, and Lenie J van den Broek, and Melanie Breetveld, and Taco Waaijman, and Stan Monstrey, and Edith M de Boer, and Rik J Scheper, and Frank B Niessen, and Susan Gibbs
October 1986, The Western journal of medicine,
Grace C Limandjaja, and Lenie J van den Broek, and Melanie Breetveld, and Taco Waaijman, and Stan Monstrey, and Edith M de Boer, and Rik J Scheper, and Frank B Niessen, and Susan Gibbs
April 1976, Postgraduate medical journal,
Copied contents to your clipboard!