ABCB5+ mesenchymal stromal cells facilitate complete and durable wound closure in recessive dystrophic epidermolysis bullosa

Abstract

Recessive dystrophic epidermolysis bullosa (RDEB) is a hereditary, rare, devastating and life-threatening skin fragility disorder with a high unmet medical need. In a recent international, single-arm clinical trial, treatment of 16patients (aged 6-36years) with three intravenous infusions of 2×106immunomodulatory ABCB5+ dermal mesenchymal stromal cells (MSCs)/kg on days0, 17 and 35 reduced disease activity, itch and pain. A post-hoc analysis was undertaken to assess the potential effects of treatment with ABCB5+ MSCs on the overall skin wound healing in patients suffering from RDEB. Documentary photographs of the affected body regions taken on days0, 17, 35 and at 12weeks were evaluated regarding proportion, temporal course and durability of wound closure as well as development of new wounds. Of 168baseline wounds in 14patients, 109 (64.9%) wounds had closed at week12, of which 63.3% (69wounds) had closed already by day35 or day17. Conversely, 74.2% of the baseline wounds that had closed by day17 or day35 remained closed until week12. First-closure ratio within 12weeks was 75.6%. The median rate of newly developing wounds decreased significantly (P=0.001) by 79.3%. Comparison of the findings with published data from placebo arms and vehicle-treated wounds in controlled clinical trials suggests potential capability of ABCB5+ MSCs to facilitate wound closure, prolongate wound recurrence and decelerate formation of new wounds in RDEB. Beyond suggesting therapeutic efficacy for ABCB5+ MSCs, the analysis might stimulate researchers who develop therapies for RDEB and other skin fragility disorders to not only assess closure of preselected target wounds but pay attention to the patients' dynamic and diverse overall wound presentation as well as to the durability of achieved wound closure and the development of new wounds. Clinicaltrials.gov NCT03529877; EudraCT 2018-001009-98.