Preclinical corrective gene transfer in Xeroderma pigmentosum human skin stem cells
| العنوان: | Preclinical corrective gene transfer in Xeroderma pigmentosum human skin stem cells |
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| المؤلفون: | Emilie Warrick, Alain Sarasin, Odile Chevallier, Marcela Del Rio, Thierry Magnaldo, Daniela Sartori, Fulvio Mavilio, Fernando Larcher, Françoise Bernerd, Marie-Françoise Avril, Marta García, Valérie Bergoglio, Corinne Chagnoleau, Jaime F. Angulo |
| المساهمون: | L'Oréal Recherche France (L'Oréal Recherche), L'OREAL, Centre européen de recherche et d'enseignement des géosciences de l'environnement (CEREGE), Institut de Recherche pour le Développement (IRD)-Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Etude des relations instabilité génétique et cancer (ERIGC), Centre National de la Recherche Scientifique (CNRS), Stabilité Génétique et Oncogenèse (UMR 8200), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Généthon, Laboratoire de Génétique de la Radiosensibilité, Département de Radiobiologie et Radiopathologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Génomes et cancer (GC (FRE2939)), Epithelial Biomedicine Division [CIEMAT Madrid], Centro de Investigaciones Energéticas Medioambientales y Tecnológicas [Madrid] (CIEMAT), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Collège de France (CdF)-Institut national des sciences de l'Univers (INSU - CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), GENETHON 3, CHU Cochin [AP-HP], Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Collège de France (CdF (institution))-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées |
| المصدر: | Molecular Therapy Molecular Therapy, Cell Press, 2012, 20 (4), pp.798-807. ⟨10.1038/mt.2011.233⟩ Molecular Therapy, 2012, 20 (4), pp.798-807. ⟨10.1038/mt.2011.233⟩ Molecular Therapy, Nature Publishing Group, 2012, 20 (4), pp.798-807. ⟨10.1038/mt.2011.233⟩ e-Archivo. Repositorio Institucional de la Universidad Carlos III de Madrid instname |
| بيانات النشر: | Academic Press, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Keratinocytes, [SDV]Life Sciences [q-bio], Human skin, 030207 dermatology & venereal diseases, 0302 clinical medicine, Drug Discovery, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, Skin, 0303 health sciences, education.field_of_study, DNA-repair, Stem Cells, Group-C protein, Flow Cytometry, 3. Good health, DNA-Binding Proteins, Blotting, Southern, medicine.anatomical_structure, Blotting, Western, Epidermis, Genetic Therapy, Humans, Real-Time Polymerase Chain Reaction, Xeroderma Pigmentosum, Molecular Biology, Molecular Medicine, Genetics, Drug Discovery3003 Pharmaceutical Science, Pharmacology, Dystrioguc epidermolysis-bullosa, Original Article, Stem cell, Keratinocyte, Human epidermal-keratinocytes, Xeroderma pigmentosum, Retroviral vectors, Medicina, Population, Biology, 03 medical and health sciences, Long-term engraftement, Transduction, In-vivo assessment, medicine, education, Clonogenic assay, 030304 developmental biology, medicine.disease, Molecular biology, Epidermal Cells, Therapy, Skin cancer, Nucleotide excision repair, Nucleotide excision-repair |
| الوصف: | Xeroderma pigmentosum (XP) is a devastating disease associated with dramatic skin cancer proneness. XP cells are deficient in nucleotide excision repair (NER) of bulky DNA adducts including ultraviolet (UV)-induced mutagenic lesions. Approaches of corrective gene transfer in NER-deficient keratinocyte stem cells hold great hope for the long-term treatment of XP patients. To face this challenge, we developed a retrovirus-based strategy to safely transduce the wild-type XPC gene into clonogenic human primary XP-C keratinocytes. De novo expression of XPC was maintained in both mass population and derived independent candidate stem cells (holoclones) after more than 130 population doublings (PD) in culture upon serial propagation (> 10(40) cells). Analyses of retrovirus integration sequences in isolated keratinocyte stem cells suggested the absence of adverse effects such as oncogenic activation or clonal expansion. Furthermore, corrected XP-C keratinocytes exhibited full NER capacity as well as normal features of epidermal differentiation in both organotypic skin cultures and in a preclinical murine model of human skin regeneration in vivo. The achievement of a long-term genetic correction of XP-C epidermal stem cells constitutes the first preclinical model of ex vivo gene therapy for XP-C patients. F.L. was supported in part by grants PI081054 from ISCIII and PBIO-0306-2006 from Comunidad de Madrid (CAM). M.D.R. was supported by grant SAF2010-16976 from MICINN. The authors declared no conflict of interest. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1525-0016 1525-0024 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e94f324583b71b0c2379856743affb73Test https://hdl.handle.net/10016/18254Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e94f324583b71b0c2379856743affb73 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15250016 15250024 |
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