ArticleEMBO molecular medicine2015
A single epidermal stem cell strategy for safe ex vivo gene therapy.
Article in EMBO molecular medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- eIF6 modulates skin wound healing by upregulating keratin 6B.Stem cells translational medicine · 2024Article
- Deciphering "Immaturity-Stemness" in Human Epidermal Stem Cells at the Levels of Protein-Coding and Non-Coding Genomes: A Prospective Computational Approach.International journal of molecular sciences · 2024Article
- Low temperature and mTOR inhibition favor stem cell maintenance in human keratinocyte cultures.EMBO reports · 2023Article
- Cytosine Deaminase Base Editing to RestoreJID innovations : skin science from molecules to population health · 2023Article
- Isolation of an "Early" Transit Amplifying Keratinocyte Population in Human Epidermis: A Role for the Low Affinity Neurotrophin Receptor CD271.Stem cells (Dayton, Ohio) · 2022Article
- Discovery and validation of human genomic safe harbor sites for gene and cell therapies.Cell reports methods · 2022Article
- Higher throughput drug screening for rare respiratory diseases: readthrough therapy in primary ciliary dyskinesia.The European respiratory journal · 2021Article
- Label-free quality control and identification of human keratinocyte stem cells by deep learning-based automated cell tracking.Stem cells (Dayton, Ohio) · 2021Article
- Stem Cell-derived Respiratory Epithelial Cell Cultures as Human Disease Models.American journal of respiratory cell and molecular biology · 2021Review
- Toward Combined Cell and Gene Therapy for Genodermatoses.Cold Spring Harbor perspectives in biology · 2020Review
- Base Editor Correction of COL7A1 in Recessive Dystrophic Epidermolysis Bullosa Patient-Derived Fibroblasts and iPSCs.The Journal of investigative dermatology · 2020Article
- Epidermolysis Bullosa-Associated Squamous Cell Carcinoma: From Pathogenesis to Therapeutic Perspectives.International journal of molecular sciences · 2019Review
- Epidermal stem cells in wound healing and their clinical applications.Stem cell research & therapy · 2019Review
- Safety and early efficacy outcomes for lentiviral fibroblast gene therapy in recessive dystrophic epidermolysis bullosa.JCI insight · 2019Article
- Clinically Relevant Correction of Recessive Dystrophic Epidermolysis Bullosa by Dual sgRNA CRISPR/Cas9-Mediated Gene Editing.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- Deletion of a Pathogenic Mutation-Containing Exon of COL7A1 Allows Clonal Gene Editing Correction of RDEB Patient Epidermal Stem Cells.Molecular therapy. Nucleic acids · 2018Article
- Regenerating human epithelia with cultured stem cells: feeder cells, organoids and beyond.EMBO molecular medicine · 2018Review
- An RNA-targeted therapy for dystrophic epidermolysis bullosa.Nucleic acids research · 2017Article
- Traceless Targeting and Isolation of Gene-Edited Immortalized Keratinocytes from Epidermolysis Bullosa Simplex Patients.Molecular therapy. Methods & clinical development · 2017Article
- RNA-based therapies for genodermatoses.Experimental dermatology · 2017Review
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14 authors.
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No grant is acknowledged in the PubMed record.
Abstract
There is a widespread agreement from patient and professional organisations alike that the safety of stem cell therapeutics is of paramount importance, particularly for ex vivo autologous gene therapy. Yet current technology makes it difficult to thoroughly evaluate the behaviour of genetically corrected stem cells before they are transplanted. To address this, we have developed a strategy that permits transplantation of a clonal population of genetically corrected autologous stem cells that meet stringent selection criteria and the principle of precaution. As a proof of concept, we have stably transduced epidermal stem cells (holoclones) obtained from a patient suffering from recessive dystrophic epidermolysis bullosa. Holoclones were infected with self-inactivating retroviruses bearing a COL7A1 cDNA and cloned before the progeny of individual stem cells were characterised using a number of criteria. Clonal analysis revealed a great deal of heterogeneity among transduced stem cells in their capacity to produce functional type VII collagen (COLVII). Selected transduced stem cells transplanted onto immunodeficient mice regenerated a non-blistering epidermis for months and produced a functional COLVII. Safety was assessed by determining the sites of proviral integration, rearrangements and hit genes and by whole-genome sequencing. The progeny of the selected stem cells also had a diploid karyotype, was not tumorigenic and did not disseminate after long-term transplantation onto immunodeficient mice. In conclusion, a clonal strategy is a powerful and efficient means of by-passing the heterogeneity of a transduced stem cell population. It guarantees a safe and homogenous medicinal product, fulfilling the principle of precaution and the requirements of regulatory affairs. Furthermore, a clonal strategy makes it possible to envision exciting gene-editing technologies like zinc finger nucleases, TALENs and homologous recombination for next-generation gene therapy.
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