Ex vivo stem cell gene therapy of the skin : Ready for clinical use?

CONCLUSIONS: The selection of the gene therapy method depends on its safety profile, the target genodermatoses and the genetic mutation to correct. PMID: 31965203 [PubMed - as supplied by publisher]
Source: Der Hautarzt: Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete - Category: Dermatology Tags: Hautarzt Source Type: research

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Publication date: 14 May 2019Source: Cell Reports, Volume 27, Issue 7Author(s): Laura De Rosa, Alessia Secone Seconetti, Giorgio De Santis, Giovanni Pellacani, Tobias Hirsch, Tobias Rothoeft, Norbert Teig, Graziella Pellegrini, Johann W. Bauer, Michele De LucaSummaryLaminin 332-deficient junctional epidermolysis bullosa (JEB) is a severe genetic skin disease. JEB is marked by epidermal stem cell depletion, the origin of which is unknown. We show that dysregulation of the YAP and TAZ pathway underpins such stem cell depletion. Laminin 332-mediated YAP activity sustains human epidermal stem cells, detected as holoclones. Abl...
Source: Cell Reports - Category: Cytology Source Type: research
Induced pluripotent stem cells (iPSCs) hold great promise for treating genetic diseases such as recessive dystrophic epidermolysis bullosa (RDEB). There are several steps common to all autologous therapeutics derived from iPSCs: reprogramming somatic cells into iPSCs, gene correction or replacement, and differentiation of iPSCs into transplantable tissue. Usually, these steps are performed sequentially which leads to a lengthy, complicated, and expensive manufacturing process. To reduce the number of steps associated with the generation of genetically corrected RDEB iPSCs, we combined our previously reported high-efficienc...
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Genetic Disease, Gene Regulation, and Gene Therapy Source Type: research
Designer nuclease-mediated gene editing constitutes a novel approach to precisely correct disease-causing gene mutations. Frame shift mutations in genes such as COL7A1, causing recessive dystrophic Epidermolysis Bullosa (RDEB), are amenable to non-homologous end joining-based corrective approaches. In previous studies using TALE nucleases designed to produce NHEJ-induced frame-restoring indels in RDEB keratinocytes, cloning, selection and expansion of corrected epidermal stem cells had been a pre-requisite to obtain sufficient cells to achieve skin regeneration with therapeutic potential.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Genetic Disease, Gene Regulation and Gene Therapy Source Type: research
Coupling the reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) with targeted gene correction using CRISPR/Cas9 offers the possibility of developing a new stem cell-based approach for the treatment of inherited skin blistering diseases such as Recessive Dystrophic Epidermolysis Bullosa (RDEB). The conventional iPSC-based therapy for RDEB involves multiple sequential steps such as reprogramming, gene correction and iPSC differentiation. Each of these steps complicates the manufacturing process and is associated with lengthy cell culture periods that increase the risk of mutation accumulation and kary...
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Genetic Disease, Gene Regulation, and Gene Therapy Source Type: research
Epidermolysis bullosa simplex (EBS) is an autosomal dominant skin fragility disorder caused by mutations in either Keratin (K) 5 or K14. Although current therapy for EBS is limited to wound care, advances in reprogramming somatic cells into induced pluripotent stem cells (iPSC) offer the possibility of developing new approaches for EBS treatment. The iPSC-based therapeutic approach for EBS relies on the generation of patient-specific iPSCs, which then undergo genetic editing and differentiation into skin cells suitable for transplantation.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Genetic Disease, Gene Regulation, and Gene Therapy Source Type: research
Coupling the reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) with targeted gene correction using CRISPR/Cas9 offers the possibility of developing a new stem cell-based approach for the treatment of inherited skin blistering diseases such as Recessive Dystrophic Epidermolysis Bullosa (RDEB). The conventional iPSC-based therapy for RDEB involves multiple sequential steps such as reprogramming, gene correction and iPSC differentiation. Each of these steps complicates the manufacturing process and is associated with lengthy cell culture periods that increase the risk of mutation accumulation and kary...
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Genetic Disease, Gene Regulation, and Gene Therapy Source Type: research
Epidermolysis bullosa simplex (EBS) is an autosomal dominant skin fragility disorder caused by mutations in either Keratin (K) 5 or K14. Although current therapy for EBS is limited to wound care, advances in reprogramming somatic cells into induced pluripotent stem cells (iPSC) offer the possibility of developing new approaches for EBS treatment. The iPSC-based therapeutic approach for EBS relies on the generation of patient-specific iPSCs, which then undergo genetic editing and differentiation into skin cells suitable for transplantation.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Genetic Disease, Gene Regulation, and Gene Therapy Source Type: research
In this study, the base of a strategy combining gene therapy and a tissue-engineered skin substitute (TES), which would be suitable for the permanent closure of skin wounds, was set-up. As a high transduction efficiency into fibroblasts and/or keratinocytes seems to be a prerequisite for a robust and sustained correction of RDEB, different envelope pseudotyped retroviral vectors and the transduction enhancer EF-C were tested. When green fluorescent protein (GFP) was used as a reporter gene to evaluate the retroviral-mediated gene transfer, the fibroblast infection efficiency was 30 % higher with the Ampho pseudotyped vecto...
Source: European Cells and Materials - Category: Cytology Tags: Eur Cell Mater Source Type: research
Nature Reviews Genetics 19, 4 (2018). doi:10.1038/nrg.2017.106 Author: Kim Baumann A publication in Nature reports the successful regeneration of ~80% of the skin of a patient with junctional epidermolysis bullosa (JEB) using a combination of ex vivo gene therapy and stem-cell replacement therapy. The procedure represents a major stepping stone in the translation
Source: Nature Reviews Genetics - Category: Genetics & Stem Cells Authors: Tags: Research Highlight Source Type: research
Ex vivo gene therapy of epidermal cells from a boy with junctional epidermolysis bullosa enabled grafts to completely replace his epidermis.Medscape Medical News
Source: Medscape Medical News Headlines - Category: Consumer Health News Tags: Dermatology News Source Type: news
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