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

BACKGROUND: 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-ß1 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-1ß 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.

Melasma en el 2021: actualización en la patogénesis y en el enfrentamiento terapéutico / Melasma in 2021: update on the pathogenesis and therapeutic coping

El Melasma es una patología con alta prevalencia a nivel mundial presente en alrededor de un 10% de la población Latinoamericana. Se caracteriza por ser una hipermelanosis cutánea adquirida que ocurre con más frecuencia en cara y cuello de mujeres con fototipos de piel III-VI de Fitzpatrick. Su patogenia aún no ha sido completamente dilucidada; sin embargo, existe evidencia que respalda la asociación del melasma con la radiación ultravioleta, la luz visible, la estimulación hormonal, factores genéticos y procesos inflamatorios. Su diagnóstico es fundamentalmente clínico, y es apoyado por instrumentos de medición que nos permiten objetivar la severidad e impacto en la calidad de vida de los pacientes afectados. El tratamiento continúa siendo un desafío ya que, si bien existen múltiples terapias que han demostrado efectividad, aún no han logrado una remisión completa, presentando una alta tasa de recurrencia. Dentro de las opciones terapéuticas destacan los tratamientos tópicos combinados, los peelings químicos y las terapias basadas en láser, sin embargo, lo más importante es hacer énfasis en la fotoprotección como medida preventiva. En esta revisión pretendemos actualizar sobre los últimos avances tanto de la fisiopatología como del tratamiento del melasma

Melasma is a pathology with a high prevalence worldwide, present in approximately 10% of the Latin American population. It is a cutaneous hypermelanosis that presents itself more frequently on the face and neck of women with Fitzpatrick skin phototypes III-VI. Its pathogenesis has not yet been fully elucidated, however, there is evidence that supports its association with ultraviolet radiation, hormonal stimulation, genetic factors, and inflammatory processes. Its diagnosis is fundamentally clinical, and is supported by clinical scores that allow us to objectify the severity and impact on the quality of life of patients who suffer from it. Treatment continues to be a challenge since, although there are multiple therapies that have demonstrated effectiveness, they have not yet achieved a complete and / or definitive remission of the disease, presenting a high recurrence rate. Treatment options include combined topical therapy, chemical peels and laser-based treatments. Much emphasis has been placed lately on photoprotection of the skin as a preventive measure. In this review we intend to update the latest advances in both the pathophysiology and treatment of melasma