A5019012569- Skin and Cellular Biology Research
- Autoimmune Bullous Skin Diseases
- Virus-based gene therapy research
- Silk-based biomaterials and applications
- RNA Interference and Gene Delivery
- Cell Adhesion Molecules Research
- Dermatological and Skeletal Disorders
- Wound Healing and Treatments
- Pluripotent Stem Cells Research
- Cellular Mechanics and Interactions
- RNA regulation and disease
- Wnt/β-catenin signaling in development and cancer
- Renal Transplantation Outcomes and Treatments
- Transgenic Plants and Applications
- Renal Diseases and Glomerulopathies
- Plant Reproductive Biology
- Tissue Engineering and Regenerative Medicine
- CRISPR and Genetic Engineering
- Immunotherapy and Immune Responses
- melanin and skin pigmentation
- Electrospun Nanofibers in Biomedical Applications
- Antimicrobial Peptides and Activities
- Hair Growth and Disorders
- Animal Genetics and Reproduction
- Viral Infectious Diseases and Gene Expression in Insects
Centre for Biomedical Network Research on Rare Diseases
2016-2025
Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas
2016-2025
Universidad Autónoma de Madrid
2014-2025
Universidad Carlos III de Madrid
2016-2025
Instituto de Salud Carlos III
2015-2025
Hospital Universitario Fundación Jiménez Díaz
2014-2024
Centro de Investigación Biomédica en Red
2013-2022
Children's Hospital at Montefiore
2005-2022
Instituto de Investigación de Enfermedades Raras
2008-2022
Fundación Botín
2001-2021
Background. Keratinocyte cultures have been used for the treatment of severe burn patients. Here, we describe a new cultured bioengineered skin based on (1) keratinocytes and fibroblasts obtained from single biopsy (2) dermal matrix human plasma. A high expansion capacity achieved by grown this plasma-based is reported. In addition, results successful preclinical clinical tests are presented. Methods. Keratinocytes were double enzymatic digestion (trypsin collagenase, respectively). setting,...
Gene editing constitutes a novel approach for precisely correcting disease-causing gene mutations. Frameshift mutations in COL7A1 causing recessive dystrophic epidermolysis bullosa are amenable to open reading frame restoration by non-homologous end joining repair-based approaches. Efficient targeted deletion of faulty exons polyclonal patient keratinocytes would enable the translation this therapeutic strategy clinic. In study, using dual single-guide RNA (sgRNA)-guided Cas9 nuclease...
Designer nucleases allow specific and precise genomic modifications represent versatile molecular tools for the correction of disease-associated mutations. In this study, we have exploited an ex vivo CRISPR/Cas9-mediated homology-directed repair approach a frequent inherited mutation in exon 80 COL7A1, which impairs type VII collagen expression, causing severe blistering skin disease recessive dystrophic epidermolysis bullosa. Upon CRISPR/Cas9 treatment patient-derived keratinocytes, using...
Brief periods of in vitro hypoxia/ischemia induce apoptosis cultured renal epithelial cells, but the underlying mechanisms remain unknown. We show that partial ATP depletion (≈10–65% control) results a duration-dependent induction Madin-Darby canine kidney (MDCK) as evidenced by internucleosomal DNA cleavage (DNA laddering and situ nick end labeling), morphological changes (cell shrinkage), plasma membrane alterations (externalization phosphatidylserine). The ATP-depleted cells display...
BACKGROUNDRecessive dystrophic epidermolysis bullosa (RDEB) is a severe form of skin fragility disorder due to mutations in COL7A1 encoding basement membrane type VII collagen (C7), the main constituent anchoring fibrils (AFs) skin. We developed self-inactivating lentiviral platform codon-optimized cDNA under control human phosphoglycerate kinase promoter for phase I evaluation.METHODSIn this single-center, open-label trial, 4 adults with RDEB each received 3 intradermal injections (~1 × 106...
From February to July of 1994, 328 faecal samples from 32 herds were collected and verotoxin-producing Escherichia coli (VTEC) found on 84% the farms. The proportion animals infected varied 0-63%. VTEC recovered 52 (20%) 257 cows 16 (23%) 71 calves. Although belonged 25 different serogroups, 7 (O8, O20, O22, O77, O113, O126 O162) accounted for 46% strains. Nearly 45% 83 bovine strains serogroups associated with haemorrhagic colitis haemolytic uraemic syndrome in humans. However, only 2 (2%)...
Abstract Human melanoma mortality is associated with the growth of metastasis in selected organs including lungs, liver, and brain. In this study, we examined consequences overexpression pigment epithelium-derived factor (PEDF), a neurotrophic potent angiogenesis inhibitor, on both primary tumor development. PEDF by cells greatly inhibited subcutaneous formation completely prevented lung liver immunocompromised mice after tail vein injection metastatic human cell lines. Whereas effects...
Netherton syndrome (NS) is a debilitating congenital skin disorder caused by mutations in the SPINK5 gene encoding lymphoepithelial Kazal-type-related inhibitor (LEKTI). It characterized defective keratinization, recurrent infections, and hypernatraemic dehydration with mortality rate of about 10% first year life. Currently, there are no curative treatments for NS. We have developed HIV-1 based, self-inactivating lentiviral vector to express keratinocytes as part an ex-vivo therapy strategy...
Abstract Non‐adherence is common in adolescent and young adult kidney transplant recipients, leading to adverse graft outcomes. The aim of this study was determine whether adherence immunosuppressant medications changes during transition from a pediatric an program within the same center. Adherence assessed for period two yr before after transfer. Subtherapeutic trough levels serum tacrolimus level variability were used as measures adherence. Twenty‐five patients transitioned between 1996...
Clonal gene therapy protocols based on the precise manipulation of epidermal stem cells require highly efficient gene-editing molecular tools. We have combined adeno-associated virus (AAV)-mediated delivery donor template DNA with transcription activator-like nucleases (TALE) expressed by adenoviral vectors to address correction c.6527insC mutation in COL7A1 gene, causing recessive dystrophic epidermolysis bullosa a high percentage Spanish patients. After transduction these viral vectors,...
Deficiency of basement membrane heterotrimeric laminin 332 component, coded by LAMA3, LAMB3, and LAMC2 genes, causes junctional epidermolysis bullosa (JEB), a severe skin adhesion defect. Herein, we report the first application CRISPR/Cas9-mediated homology direct repair (HDR) to in situ restore LAMB3 expression JEB keratinocytes vitro immunodeficient mice transplanted with genetically corrected equivalents. We packaged an adenovector carrying Cas9/guide RNA (gRNA) tailored intron 2 gene...
Recessive dystrophic epidermolysis bullosa (RDEB), Kindler syndrome (KS) and xeroderma pigmentosum complementation group C (XPC) are three cancer‐prone genodermatoses whose causal genetic mutations cannot fully explain, on their own, the array of associated phenotypic manifestations. Recent evidence highlights role stromal microenvironment in pathology these disorders. To investigate, by means comparative gene expression analysis, played dermal fibroblasts pathogenesis RDEB, KS XPC. We...
Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a genodermatosis characterized by severe cutaneous and mucosal fragility, frequently complicated multifactorial chronic anemia that responds poorly to conventional therapies. This cross-sectional study investigates the factors contributing in RDEB analyzing representative cohort, was stratified disease severity, iron status, examine their hematological parameters, cytokine profile erythropoietin (EPO)-erythroferrone (ERFE)-hepcidin axis....
Although skin is perhaps the most accessible of all somatic tissues for therapeutic gene transfer, it a challenging site when attempting delivery. In addition to transience expression, important obstacles cutaneous therapy have included inability sustain expression in large proportion keratinocytes within given compartment. this study, we developed novel experimental strategy that allows long-term regeneration entirely genetically engineered human on backs NOD/SCID mice. Primary were...
We have shown that retroviral vectors efficiently transfer the 9-kb collagen type VII cDNA into keratinocytes of dogs with recessive dystrophic epidermolysis bullosa (RDEB) and achieve correction RDEB phenotype in vitro. As a next step toward gene therapy applications, we assessed suitability to transduce human primary generate transplantable autologous skin equivalents. The transduced permanently express high levels recombinant assembles functional homotrimers readily secreted extracellular...