Original articleSuccessful therapeutic transplantation of revertant skin in epidermolysis bullosa
Section snippets
Patient and intervention
Patient 029-01, a 69-year-old man with non-Herlitz junctional EB caused by a homozygous splice-site mutation in the LAMB3 gene (c.628G>A) had been confined to a wheelchair since 1993 after transfemoral left leg amputation as a result of cutaneus squamous cell carcinoma.15 He presented with 7 persistent (>1 year) and painful ulcers: 6 on the lower aspect of his back (Fig 1, B) and 1 on his right foot. The total area of the ulcers was 7 cm2 and no signs of malignancy were present. On the
Results
Inspection took place 5 and 7 days after the procedure during which adequate wound healing and no signs of infection were observed. All 73 transplanted punch biopsy specimens were accepted in the grafted area and complete re-epithelialization occurred within 14 days (Fig 1, D and E). Interestingly, 21 days after the procedure a blister appeared next to one of the treated ulcers. The blister did not spread into the transplanted area (Fig 1, D), suggesting that the healthy phenotype had been
Discussion
Transplantation of revertant skin, and therefore expansion of healthy, disease-free skin, can highly improve quality of life in patients with EB. Earlier attempts, focused on cultured skin equivalents, were not successful because of an insufficient amount of revertant cells in the grafts (<3%).14 In this report we show that both donor and acceptor sites healed with revertant epidermis and expressed amounts of laminin-332 comparable with normal-appearing human skin. Moreover, by tracing the
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Cited by (63)
The Past and Future of Rare Skin Disease Research and Therapy
2022, Journal of Investigative DermatologyCurrent topics in Epidermolysis bullosa: Pathophysiology and therapeutic challenges
2021, Journal of Dermatological ScienceRecombination-induced revertant mosaicism in ichthyosis with confetti and loricrin keratoderma
2020, Journal of Dermatological ScienceCitation Excerpt :Notably, HR is the only reported reversion mechanism in these disorders; all investigated revertant epidermis samples showed characteristic long-tract LOH that originated from regions centromeric to pathogenic mutations and extended to the telomere [16–18,39,42]. To date, some therapeutic attempts using revertant skin patches or keratinocytes, including successful therapeutic transplantation of revertant skin for refractory skin ulcers in a patient with non-Herlitz junctional EB [51] and successful establishment of mutation-free induced pluripotent stem cells generated from revertant junctional or recessive dystrophic EB keratinocytes [52,53], have been reported. Elucidating the molecular basis of revertant mosaicism—especially how mutant proteins induce long-tract LOH—could expand the possibility of manipulating HR to induce the reversion of disease-causing mutations, and potentially benefit patients with IWC and LK, as well as other currently intractable genetic diseases.
Cultured Epidermal Autografts from Clinically Revertant Skin as a Potential Wound Treatment for Recessive Dystrophic Epidermolysis Bullosa
2019, Journal of Investigative DermatologyCitation Excerpt :Very few attempts to treat EB ulcers with RM have been reported. Gostyński and colleagues successfully performed full-thickness skin grafting from revertant areas to refractory ulcers in a patient with JEB (Gostyński et al., 2014). CEA treatment involving RM was performed by the same group for a patient with JEB, but the clinical effect was reported to be unsatisfactory (Gostyński et al., 2009).
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2024, International Journal of Molecular SciencesNew treatments for epidermolysis bullosa management
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Funded by the Dutch Butterfly Child Foundation (Stichting Vlinderkind).
Conflicts of interest: None declared.