Allogeneic fibroblast cell therapy in the treatment of recessive dystrophic epidermolysis bullosa

Kubanov, Alexey А.; Карамова, А. Э.; Albanova, V. I.; Смольянникова, В А; Nefedova, M. A.; Чикин, В. В.; Monchakovskaya, Ekaterina S.

doi:10.1016/j.wndm.2018.04.002

Cited by 6 publications

(4 citation statements)

References 14 publications

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“…Несмотря на проведение исследований по разработке новых патогенетических методов терапии врожденного буллезного эпидермолиза, в настоящее время возможно использование средств только симптоматической терапии [69]. Поскольку пациентам назначается симптоматическая терапия, следует ожидать от нее не более чем временного эффекта.…”

Section: заключениеunclassified

Topical treatment of inherited epidermolysis bullosa

Kubanov

Чикин

Карамова

et al. 2021

Vestnik dermatologii i venerologii

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Inherited epidermolysis bullosa is a group of genetic skin disorders characterized by skin erosions, ulceration, skin and mucosal blistering requiring topical treatment. This review demonstrates major clinical manifestations of epidermolysis bullosa and its mechanisms of development. According to these features the main principles of topical treatment and drug therapy were developed, including physical protection from trauma, moisturizing, improvement of wound healing, prevention and management of infection, itch and pain management. Drug therapy is outlined with dosage forms, drug routes of administration, age restrictions indicated in the instruction for medical use for the medications that could be used in epidermolysis bullosa patients. The authors provide indications for clinical use of antiseptics, disinfectants, antibiotics, antimicrobial agents, emollient cream and drugs reducing itch and pain.

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Section: заключениеunclassified

Topical treatment of inherited epidermolysis bullosa

Kubanov

Чикин

Карамова

et al. 2021

Vestnik dermatologii i venerologii

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“…Reductions or functional impairments in C7 can therefore lead to the generation of severe and poorly healing blisters following minor mechanical trauma, which can translate into more systemic and life-threatening complications. 2 In the absence of a cure, a variety of therapeutic strategies are being investigated including allogeneic fibroblast therapy, 3 protein replacement therapy (Clinical Trial Identifier #NCT03752905), and a transiently expressed gene therapy. 4 However, as these approaches fail to address the underlying genetic mutation, they are unable to provide a permanent cure.…”

Section: Introductionmentioning

confidence: 99%

“…In the absence of a cure, a variety of therapeutic strategies are being investigated including allogeneic fibroblast therapy, 3 protein replacement therapy (Clinical Trial Identifier #NCT03752905), and a transiently expressed gene therapy. 4 However, as these approaches fail to address the underlying genetic mutation, they are unable to provide a permanent cure.…”

Section: Introductionmentioning

confidence: 99%

Highly efficient CRISPR/Cas9‐mediated exon skipping for recessive dystrophic epidermolysis bullosa

du Rand,

Hunt,

Samson

et al. 2024

Bioengineering & Transla Med

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Gene therapy based on the CRISPR/Cas9 system has emerged as a promising strategy for treating the monogenic fragile skin disorder recessive dystrophic epidermolysis bullosa (RDEB). With this approach problematic wounds could be grafted with gene edited, patient‐specific skin equivalents. Precise gene editing using homology‐directed repair (HDR) is the ultimate goal, however low efficiencies have hindered progress. Reframing strategies based on highly efficient non‐homologous end joining (NHEJ) repair aimed at excising dispensable, mutation‐harboring exons offer a promising alternative approach for restoring the COL7A1 open reading frame. To this end, we employed an exon skipping strategy using dual single guide RNA (sgRNA)/Cas9 ribonucleoproteins (RNPs) targeted at three novel COL7A1 exons (31, 68, and 109) containing pathogenic heterozygous mutations, and achieved exon deletion rates of up to 95%. Deletion of exon 31 in both primary human RDEB keratinocytes and fibroblasts resulted in the restoration of type VII collagen (C7), leading to increased cellular adhesion in vitro and accurate C7 deposition at the dermal‐epidermal junction in a 3D skin model. Taken together, we extend the list of COL7A1 exons amenable to therapeutic deletion. As an incidental finding, we find that long‐read Nanopore sequencing detected large on‐target structural variants comprised of deletions up to >5 kb at a frequency of ~10%. Although this frequency may be acceptable given the high rates of intended editing outcomes, our data demonstrate that standard short‐read sequencing may underestimate the full range of unexpected Cas9‐mediated editing events.

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“…Nevertheless, various cell types could be studied for cell-based approaches to the treatment -specifically, fibroblasts that are characterized by low immunogenicity and easy cultivation. Several publications reported the efficacy of allogeneic fibroblasts in the treatment of recessive dystrophic epidermolysis bullosa patients [10,11].…”

Section: Introductionmentioning

confidence: 99%

Efficacy Of Intradermal Allogeneic Fibroblast Injections In Junctional Epidermolysis Bullosa

et al. 2022

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Objective — to assess the efficacy and safety of intradermal injections of allogeneic fibroblasts into non-healing wounds in a patient with junctional epidermolysis bullosa. Material and Methods — A 49-year-old patient with intermediate junctional epidermolysis bullosa was injected intradermally into the base of non-healing wounds with 1 mL suspension of allogeneic fibroblasts, which contained 5×106 cells/mL, 10×106 cells/mL, and 20×106 cells/mL. Immunofluorescence mapping exhibited reduced β3 chain of laminin 332 and collagen XVII expression in the basement membrane area. Paired erosions were injected with 2% albumin or saline solution. Results — At two weeks after treatment, wound areas reduced significantly, or 100% re-epithelialization occurred. Collagen XVII and β3 chain expression of laminin 332 increased at the dermal-epidermal junction. Conclusion — Our findings demonstrated that intradermal injections of allogeneic fibroblasts could be an effective therapeutic approach for treating small non-healing wounds in junctional epidermolysis bullosa.

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Allogeneic fibroblast cell therapy in the treatment of recessive dystrophic epidermolysis bullosa

Cited by 6 publications

References 14 publications

Topical treatment of inherited epidermolysis bullosa

Topical treatment of inherited epidermolysis bullosa

Highly efficient CRISPR/Cas9‐mediated exon skipping for recessive dystrophic epidermolysis bullosa

Efficacy Of Intradermal Allogeneic Fibroblast Injections In Junctional Epidermolysis Bullosa

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