Abstract
Background and aims: 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 16 patients (aged 6–36 years) with three intravenous infusions of 2 × 106 immunomodulatory ABCB5+ dermal mesenchymal stromal cells (MSCs)/kg on days 0, 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. Methods: Documentary photographs of the affected body regions taken on days 0, 17, 35 and at 12 weeks were evaluated regarding proportion, temporal course and durability of wound closure as well as development of new wounds. Results: Of 168 baseline wounds in 14 patients, 109 (64.9%) wounds had closed at week 12, of which 63.3% (69 wounds) had closed already by day 35 or day 17. Conversely, 74.2% of the baseline wounds that had closed by day 17 or day 35 remained closed until week 12. First-closure ratio within 12 weeks was 75.6%. The median rate of newly developing wounds decreased significantly (P = 0.001) by 79.3%. Conclusions: 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. Trial registration: Clinicaltrials.gov NCT03529877; EudraCT 2018-001009-98.
Original language | English (US) |
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Pages (from-to) | 782-788 |
Number of pages | 7 |
Journal | Cytotherapy |
Volume | 25 |
Issue number | 7 |
DOIs | |
State | Published - Jul 2023 |
Bibliographical note
Funding Information:Contributions by NYF and MHF to this work were supported by the National Institutes of Health (NIH)/National Eye Institute (NEI) grants RO1EY025794 and R24EY028767 , NIH National Heart, Lung, and Blood Institute (NHLBI) grant 1R01HL16108 7, and NIH National Institute on Aging 1P01AG071463. Contributions by DK were supported by the Berta-Ottenstein Advanced Clinician Scientist Programme of the University of Freiburg and by the German Research Foundation (DFG) through KI1795/2-1, the CRC1160/2 – project B03(N) and the CRC-1479 – Project ID: 441891347. The funding sources had no involvement in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.
Publisher Copyright:
© 2023 International Society for Cell & Gene Therapy
Keywords
- ABCB5
- inflammation
- mesenchymal stromal cells
- recessive dystrophic epidermolysis bullosa
- wound healing
PubMed: MeSH publication types
- Journal Article
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't