CRIS

Permanent URI for this communityhttps://investigadores.udd.cl/handle/123456789/1

Browse

Settings

Access type: UnknownSubject: search.filters.subject.epidermolysis bullosa dystrophica

Search Results

Now showing 1 - 10 of 13
  • Loading...
    Thumbnail Image
    Some of the metrics are blocked by your 
    consent settings
    Item type:Publication,
    Paw Skin as a Translational Model for Investigating Fibrotic and Inflammatory Wound Healing Defects in Recessive Dystrophic Epidermolysis Bullosa
    (MDPI AG, 2025-04-30)
    DE GREGORIO CONCHA, CRISTIAN ALEJANDRO  
    ;
    Giselle Ramos-Gonzalez
    ;
    Bernardo Morales-Catalán
    ;
    EZQUER, EDUARDO FERNANDO  
    ;
    EZQUER, EDUARDO MARCELO  
    Recessive dystrophic epidermolysis bullosa (RDEB) is a severe genetic disease caused by COL7A1 mutations. It leads to skin fragility, chronic inflammation, and impaired wound healing. The condition often results in fibrotic scarring, pseudosyndactyly, and cutaneous squamous cell carcinoma (SCC). However, current animal models fail to fully replicate chronic RDEB wounds. In this study, we used Collagen VII-hypomorphic mice (Col7a1flNeo/flNeo) and created full-thickness wounds on their paw skin, an area prone to fibrosis due to mechanical stress. We analyzed the healing process using histology, immunofluorescence, and electron microscopy. The RDEB mice showed delayed wound closure, increased inflammation, and poor granulation tissue formation. At 30 days post-injury, we observed persistent fibrosis, with elevated levels of Collagen I, α-SMA+ myofibroblasts, and tenascin-C. These mice also had fewer intraepidermal nerve fibers, which may help explain the neuropathic pain associated with RDEB. Our model reproduces the main features of chronic RDEB wounds. It offers a useful tool for evaluating therapies aimed at reducing inflammation, fibrosis, and tumor risk in these patients.
    Scopus© Citations 3  4
  • Loading...
    Thumbnail Image
    Some of the metrics are blocked by your 
    consent settings
    Item type:Publication,
    Pregabalin for Neuropathic Pain and Itch in Recessive Dystrophic Epidermolysis Bullosa
    (American Medical Association (AMA), 2024-12-01)
    Margarita Calvo
    ;
    Macarena Tejos-Bravo
    ;
    Alvaro Passi-Solar
    ;
    Fernanda Espinoza
    ;
    FUENTES BUSTOS, MARIA IGNACIA  
    <jats:sec><jats:title>Importance</jats:title><jats:p>Patients with recessive dystrophic epidermolysis bullosa (RDEB) experience neuropathic pain and itch. There is a lack of evidence on any treatment for these symptoms in patients with RDEB.</jats:p></jats:sec><jats:sec><jats:title>Objectives</jats:title><jats:p>To test the efficacy of pregabalin in the treatment of neuropathic pain and itch in patients with RDEB.</jats:p></jats:sec><jats:sec><jats:title>Design, Setting, and Participants</jats:title><jats:p>A randomized, double-blinded, crossover trial of oral pregabalin (50-300 mg/d) vs placebo was conducted at 2 sites, Toronto (Canada) and Santiago (Chile) from January 1, 2019, to December 31, 2020. Patients eligible to participate were diagnosed with RDEB, aged 8 to 40 years, not pregnant or lactating (if female), and had evidence of probable neuropathic pain and itching defined as distal thermal sensory loss (confirmed by thermal roller), score of 4 or greater on the <jats:italic>Douleur Neuropathique</jats:italic> 4 questionnaire (DN4), and score greater than 4 on the 10-point visual analog scale [VAS]). Patients with a clinically important or poorly controlled medical or psychiatric condition or pregabalin intolerance or allergy were excluded. Of 41 patients screened, 3 were not eligible and 28 declined enrollment. Data analyses were performed in 2021 through 2023.</jats:p></jats:sec><jats:sec><jats:title>Intervention</jats:title><jats:p>Participants received both pregabalin and matched placebo (titrated to a maximum-tolerated dose of 300 mg/day) in a randomized sequence so that comparisons could be made within participants and between groups.</jats:p></jats:sec><jats:sec><jats:title>Main Outcomes and Measures</jats:title><jats:p>Difference in the mean pain and itch scores between pregabalin and placebo treatment (measured using VAS) before and after intervention.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>In all, 10 participants were randomized to 2 groups, 6 patients (mean [SD] age, 26.7 [8.1] years; 3 females [50%]) in group 1, and 4 patients (mean [SD] age, 26.5 [7.8] years, 2 females [50%]) in group 2. Group 1 received a sequence of pregabalin-placebo while group 2 received placebo-pregabalin. Pregabalin significantly reduced mean (SD) pain scores by 1.9 (1.5) points when controlling for sequence and treatment period vs baseline, while placebo had 0.1 (2.0) points of reduction. The effect of pregabalin was a mild but significant reduction in itch compared to baseline (mean [SD] points, 0.9 [2.2]), whereas the placebo produced no reduction (0.1 [2.5]). The mean pregabalin dose was generally well tolerated.</jats:p></jats:sec><jats:sec><jats:title>Conclusions and Relevance</jats:title><jats:p>The results of this randomized crossover trial indicate that pregabalin significantly reduced pain and itch scores from baseline compared to placebo in patients with RDEB. This feasibility study provided preliminary data on the efficacy of pregabalin in managing pain and itch in RDEB and gathered essential data to inform the design of a larger cohort trial.</jats:p></jats:sec><jats:sec><jats:title>Trial Registration</jats:title><jats:p>ClinicalTrials.gov Identifier: <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://clinicaltrials.gov/study/NCT03928093">NCT03928093</jats:ext-link></jats:p></jats:sec>
    Scopus© Citations 3  2
  • Loading...
    Thumbnail Image
    Some of the metrics are blocked by your 
    consent settings
    Item type:Publication,
    Maintenance of chronicity signatures in fibroblasts isolated from recessive dystrophic epidermolysis bullosa chronic wound dressings under culture conditions
    (2023)
    DE GREGORIO CONCHA, CRISTIAN ALEJANDRO  
    ;
    Evelyng Catalán
    ;
    Gabriel Garrido
    ;
    Pilar Morandé
    ;
    CASTILLO BENNETT, JIMENA VICTORIA  
    <jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a rare inherited skin disease caused by variants in the <jats:italic>COL7A1</jats:italic> 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.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>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.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>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.</jats:p> </jats:sec>
    Scopus© Citations 1  1
  • Loading...
    Thumbnail Image
    Some of the metrics are blocked by your 
    consent settings
    Item type:Publication,
    Collagen VII maintains proteostasis in dermal fibroblasts by scaffolding TANGO1 cargo
    (2022)
    Qingqing Cao
    ;
    Grace Tartaglia
    ;
    Michael Alexander
    ;
    Pyung Hung Park
    ;
    Shiv Poojan
    Scopus© Citations 9  7
  • Loading...
    Thumbnail Image
    Some of the metrics are blocked by your 
    consent settings
    Item type:Publication,
    Characterisation of the pathophysiology of neuropathy and sensory dysfunction in a mouse model of recessive dystrophic epidermolysis bullosa
    (2022)
    Daniela Schmidt
    ;
    Paula Díaz
    ;
    Daniela Muñoz
    ;
    Fernanda Espinoza
    ;
    Alexander Nystrom
      32Scopus© Citations 7
  • Loading...
    Thumbnail Image
    Some of the metrics are blocked by your 
    consent settings
    Item type:Publication,
    Scopus© Citations 7  1
  • Loading...
    Thumbnail Image
    Some of the metrics are blocked by your 
    consent settings
    Item type:Publication,
    Scopus© Citations 11  2
  • Loading...
    Thumbnail Image
    Some of the metrics are blocked by your 
    consent settings
    Item type:Publication,
      19Scopus© Citations 7
  • Loading...
    Thumbnail Image
    Some of the metrics are blocked by your 
    consent settings
    Item type:Publication,
    Consensus reclassification of inherited epidermolysis bullosa and other disorders with skin fragility
    (2020)
    C. Has
    ;
    J.W. Bauer
    ;
    C. Bodemer
    ;
    M.C. Bolling
    ;
    L. Bruckner‐Tuderman
      25Scopus© Citations 665
  • Loading...
    Thumbnail Image
    Some of the metrics are blocked by your 
    consent settings
    Item type:Publication,
      9