Introduction: Combinatorial cell and gene therapies for life-threatening inherited skin disorders have shown tremendous potential for preclinical and clinical implementation with significant progress made for recessive dystrophic epidermolysis bullosa (RDEB). To date, various cell lineages including resident skin cells and adult stem cells have been investigated for gene and cell therapy for RDEB reaching the clinical trial stage.
Sources of data: Sources of data are key recent literature, ClinicalTrials.gov, Clinicaltrialsregister.eu and pharma press releases.
Areas of agreement: Cell-based gene transfer using autologous patients' cells has demonstrated positive outcomes in preclinical and clinical trials and highlighted the importance of targeting resident skin stem cells to achieve a meaningful long-term effect. Additionally, adult stem cells, such as mesenchymal stromal cells, have the potential to ameliorate systemic manifestations of the disease.
Areas of controversy: While proven safe, the clinical trials of localized treatment have reported only modest and transient improvements. On the other hand, the risks associated with systemic therapies remain high and should be carefully weighed against the potential benefits. It is unclear to what extent adult stem cells can contribute to skin regeneration/wound healing.
Growing points: Further research is warranted in order to fulfil the potential of cellular therapies for RDEB. The development of combinatorial gene and cell-based approaches is required to achieve long-term clinical benefits.
Areas timely for developing research: Induced pluripotent stem cells can potentially provide a valuable source of autologous patient material for cellular therapies. In addition, recent advances in the field of gene editing can overcome hurdles associated with conventional gene addition approaches.
Data availability statement: No new data were generated or analysed in support of this review.
Keywords: MSCs; RDEB; cell therapy; gene therapy; iPSCs; skin cells.
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