Maintenance of chronicity signatures in fibroblasts isolated from recessive dystrophic epidermolysis bullosa chronic wound dressings under culture conditions

Biological Research

Research Article

Marcelo Ezquer¹  Cristian De Gregorio¹  Bárbara Cuadra¹  Ya-Lin Huang¹  Jimena Castillo Bennett²  Gabriel Garrido²  Evelyng Catalán²  Pilar Morandé²  Glenda Cofré²  Catalina Muñoz²  Ignacia Fuentes³  María Joao Yubero⁴  Francis Palisson⁵  Andrew P. South⁶  Fernando Altermatt⁷  Margarita Calvo⁸  Paola Murgas⁹ 

[1] Centro de Medicina Regenerativa, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, 7610658, Santiago, Chile;DEBRA Chile, Francisco de Villagra 392, Ñuñoa, Santiago, Chile;DEBRA Chile, Francisco de Villagra 392, Ñuñoa, Santiago, Chile;Centro de Genética y Genómica, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, 7610658, Santiago, Chile;Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile;DEBRA Chile, Francisco de Villagra 392, Ñuñoa, Santiago, Chile;Pediatrics and Pediatric Infectious Diseases of Clínica Alemana, Facultad de Medicina Alemana, Universidad del Desarrollo, Santiago, Chile;DEBRA Chile, Francisco de Villagra 392, Ñuñoa, Santiago, Chile;Servicio de Dermatología, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Santiago, Chile;Department of Dermatology & Cutaneous Biology, Thomas Jefferson University, Philadelphia, USA;División de Anestesiología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile;Facultad de Ciencias Biológicas y División de Anestesiología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile;Núcleo milenio para el estudio del dolor MINUSPAIN, Santiago, Chile;Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile;

关键词: Recessive Dystrophic Epidermolysis Bullosa;    Skin fibroblast;    Chronic Wounds;    Wound Dressing;    Fibrosis;   

DOI  :  10.1186/s40659-023-00437-2

 received in 2022-11-30, accepted in 2023-04-27,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundRecessive Dystrophic Epidermolysis Bullosa (RDEB) is a rare inherited skin disease caused by variants in the COL7A1 gene, coding for type VII collagen (C7), an important component of anchoring fibrils in the basement membrane of the epidermis. RDEB patients suffer from skin fragility starting with blister formation and evolving into chronic wounds, inflammation and skin fibrosis, with a high risk of developing aggressive skin carcinomas. Restricted therapeutic options are limited by the lack of in vitro models of defective wound healing in RDEB patients.ResultsIn order to explore a more efficient, non-invasive in vitro model for RDEB studies, we obtained patient fibroblasts derived from discarded dressings) and examined their phenotypic features compared with fibroblasts derived from non-injured skin of RDEB and healthy-donor skin biopsies. Our results demonstrate that fibroblasts derived from RDEB chronic wounds (RDEB-CW) displayed characteristics of senescent cells, increased myofibroblast differentiation, and augmented levels of TGF-β1 signaling components compared to fibroblasts derived from RDEB acute wounds and unaffected RDEB skin as well as skin from healthy-donors. Furthermore, RDEB-CW fibroblasts exhibited an increased pattern of inflammatory cytokine secretion (IL-1β and IL-6) when compared with RDEB and control fibroblasts. Interestingly, these aberrant patterns were found specifically in RDEB-CW fibroblasts independent of the culturing method, since fibroblasts obtained from dressing of acute wounds displayed a phenotype more similar to fibroblasts obtained from RDEB normal skin biopsies.ConclusionsOur results show that in vitro cultured RDEB-CW fibroblasts maintain distinctive cellular and molecular characteristics resembling the inflammatory and fibrotic microenvironment observed in RDEB patients’ chronic wounds. This work describes a novel, non-invasive and painless strategy to obtain human fibroblasts chronically subjected to an inflammatory and fibrotic environment, supporting their use as an accessible model for in vitro studies of RDEB wound healing pathogenesis. As such, this approach is well suited to testing new therapeutic strategies under controlled laboratory conditions.

【 授权许可】

CC BY   
© The Author(s) 2023

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