ArticleStem cell research & therapy2026
Identification of a long-term surviving human mesenchymal stromal cell subpopulation and implications for recessive dystrophic epidermolysis bullosa treatment.
Article in Stem cell research & therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundRecessive dystrophic epidermolysis bullosa (RDEB) is a severe skin disease caused by loss-of-function pathogenic variants in COL7A1 encoding type VII collagen (C7). Patients with RDEB suffer since birth from skin and mucosal blistering and develop severe local and systemic complications resulting in poor prognosis. Mesenchymal stromal cells (MSCs) have demonstrated their potential to enhance wound healing and reduce skin inflammation in RDEB patients due to their anti-inflammatory properties and capacity to express C7. We aim to optimize in vitro conditioning of human bone marrow-derived MSCs (BM-MSCs) to improve their limited survival following local injection in a murine model.
methodsBM-MSCs from healthy human donors were transduced with a lentiviral vector encoding firefly luciferase and mCherry reporter proteins and then subjected to various culture conditions: monolayer on plastic or spheroid culture, either in hypoxia (5% O
resultsscRNAseq analysis revealed marked variations between monolayer and spheroid conditions, which were significantly impacted by oxygen level. Although most injected cells gradually died within the first 2 months in all tested conditions, 1% of live bioluminescent cells persisted for 54 up to 61 weeks post-injection. Spatial transcriptomics data analysis demonstrated that all surviving cells, regardless of their in vitro preconditioning, retained the expression of the MSC markers THY1, ENG, and NT5E, shared features with fibroblasts, and exhibited enriched expression in genes related to extracellular matrix and collagen fibril organization, which are key processes in wound healing. Spatial transcriptomic and scRNAseq data integration suggested that surviving BM-MSCs were initially present in the injected population, regardless of their culture condition. Remarkably, none of the in vitro preconditioning strategies appeared to affect their survival capacity or functional properties following local injection.
conclusionsThe identification and characterization of a BM-MSC subpopulation capable of long-term survival following ID injection hold promise for the development of improved cell therapy protocols for RDEB.
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