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

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dc.contributor.authorDe Gregorio, Cristian
dc.contributor.authorCatalán, Evelyng
dc.contributor.authorGarrido, Gabriel
dc.contributor.authorMorandé, Pilar
dc.contributor.authorCastillo, Jimena
dc.contributor.authorMuñoz, Catalina
dc.contributor.authorCofré, Glenda
dc.contributor.authorHuang, Ya-Lin
dc.contributor.authorCuadra, Bárbara
dc.contributor.authorMurgas, Paola
dc.contributor.authorCalvo, Margarita
dc.contributor.authorAltermatt, Fernando
dc.contributor.authorJoao, María
dc.contributor.authorPalisson, Francis
dc.contributor.authorSouth, Andrew
dc.contributor.authorEzquer, Marcelo
dc.contributor.authorEzquer, Marcelo
dc.contributor.authorFuentes, Ignacia
dc.date.accessioned2024-05-06T16:46:43Z
dc.date.available2024-05-06T16:46:43Z
dc.date.issued2023
dc.description.abstractBackground: Recessive 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. Results: In 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. Conclusions: Our 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.
dc.description.versionAceptada
dc.identifier.citationGregorio, Cristian De, Catalán, Evelyng, Garrido, Gabriel, Morandé, Pilar, Castillo Bennett, Jimena, Muñoz, Catalina, Cofré, Glenda, Huang, Ya-Lin, Cuadra, Bárbara, Murgas, Paola, Calvo, Margarita, Altermatt, Fernando, Joao Yubero, María, Palisson, Francis, South, Andrew P., Ezquer, Marcelo, & Fuentes, Ignacia. (2023). Maintenance of chronicity signatures in fibroblasts isolated from recessive dystrophic epidermolysis bullosa chronic wound dressings under culture conditions. Biological Research, 56, 23. Epub 26 de mayo de 2023.https://dx.doi.org/10.1186/s40659-023-00437-2
dc.identifier.doihttps://doi.org/10.1186/s40659-023-00437-2
dc.identifier.urihttps://hdl.handle.net/11447/8709
dc.language.isoen
dc.subjectRecessive Dystrophic Epidermolysis Bullosa
dc.subjectSkin fibroblast
dc.subjectChronic Wounds
dc.subjectWound Dressing
dc.subjectFibrosis
dc.titleMaintenance of chronicity signatures in fibroblasts isolated from recessive dystrophic epidermolysis bullosa chronic wound dressings under culture conditions
dc.typeArticle
dcterms.accessRightsAcceso Abierto
dcterms.sourceBiological Research
dspace.entity.typePublication
relation.isAuthorOfPublication9cd4a8e6-6ba1-4344-80a2-45c260864d4c
relation.isAuthorOfPublication.latestForDiscovery9cd4a8e6-6ba1-4344-80a2-45c260864d4c

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