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

Dieter, Kathrin; Niebergall-Roth, Elke; Daniele, Cristina; Fluhr, Silvia; Frank, Natasha Y.; Ganss, Christoph; Kiritsi, Dimitra; McGrath, John A.; Tolar, Jakub; Frank, Markus H.; Kluth, Mark A.

doi:10.1016/j.jcyt.2023.01.015

Cited by 9 publications

(12 citation statements)

References 39 publications

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“…In human RDEB patients, intravenous infusions of allogeneic ABCB5 + MSCs distinctly increased wound closure parameters superior to historical placebo data. Importantly, about 75% of the closed wounds remained durably closed for at least 7 or even 9.5 weeks [188], which exceeds the typical natural recurrency period of RDEB wounds of roughly 3 weeks on average [189]. Even in the wounds that did not reach full closure during the 12-week efficacy follow-up period, intravenously infused ABCB5 + MSCs elicited significant mean decreases in wound size [188].…”

Section: Recessive Dystrophic Epidermolysis Bullosamentioning

confidence: 91%

“…Importantly, about 75% of the closed wounds remained durably closed for at least 7 or even 9.5 weeks [188], which exceeds the typical natural recurrency period of RDEB wounds of roughly 3 weeks on average [189]. Even in the wounds that did not reach full closure during the 12-week efficacy follow-up period, intravenously infused ABCB5 + MSCs elicited significant mean decreases in wound size [188]. Moreover, the treatment significantly decelerated the formation of new wounds [188].…”

Section: Recessive Dystrophic Epidermolysis Bullosamentioning

confidence: 91%

“…Even in the wounds that did not reach full closure during the 12-week efficacy follow-up period, intravenously infused ABCB5 + MSCs elicited significant mean decreases in wound size [188]. Moreover, the treatment significantly decelerated the formation of new wounds [188]. Additionally, ABCB5 + MSCs infusions significantly alleviated patient-perceived pruritus, which is consistently rated as the most bothersome symptom in RDEB, and reduced disease severity as measured by clinically meaningful reductions in two relevant disease severity scores, i.e., the Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) activity score and the Instrument for Scoring Clinical Outcome of Research for Epidermolysis Bullosa (iscorEB) clinician score [166].…”

Section: Recessive Dystrophic Epidermolysis Bullosamentioning

confidence: 98%

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Skin-Derived ABCB5+ Mesenchymal Stem Cells for High-Medical-Need Inflammatory Diseases: From Discovery to Entering Clinical Routine

Niebergall-Roth¹,

Frank

Ganss

et al. 2022

IJMS

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The ATP-binding cassette superfamily member ABCB5 identifies a subset of skin-resident mesenchymal stem cells (MSCs) that exhibit potent immunomodulatory and wound healing-promoting capacities along with superior homing ability. The ABCB5+ MSCs can be easily accessed from discarded skin samples, expanded, and delivered as a highly homogenous medicinal product with standardized potency. A range of preclinical studies has suggested therapeutic efficacy of ABCB5+ MSCs in a variety of currently uncurable skin and non-skin inflammatory diseases, which has been substantiated thus far by distinct clinical trials in chronic skin wounds or recessive dystrophic epidermolysis bullosa. Therefore, skin-derived ABCB5+ MSCs have the potential to provide a breakthrough at the forefront of MSC-based therapies striving to fulfill current unmet medical needs. The most recent milestones in this regard are the approval of a phase III pivotal trial of ABCB5+ MSCs for treatment of recessive dystrophic and junctional epidermolysis bullosa by the US Food and Drug Administration, and national market access of ABCB5+ MSCs (AMESANAR®) for therapy-refractory chronic venous ulcers under the national hospital exemption pathway in Germany.

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Section: Recessive Dystrophic Epidermolysis Bullosamentioning

confidence: 91%

Section: Recessive Dystrophic Epidermolysis Bullosamentioning

confidence: 91%

Section: Recessive Dystrophic Epidermolysis Bullosamentioning

confidence: 98%

See 1 more Smart Citation

Skin-Derived ABCB5+ Mesenchymal Stem Cells for High-Medical-Need Inflammatory Diseases: From Discovery to Entering Clinical Routine

Niebergall-Roth¹,

Frank

Ganss

et al. 2022

IJMS

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“…In addition, following systemic intravenous grafting, ABCB5 + MSCs reduced RDEB symptoms and significantly prolonged the lifespan in a Col7a1 -/mouse model of RDEB [18]. Very recently we found that three intravenous infusions of allogeneic skin-derived ABCB5 + MSCs to patients with RDEB decreased disease activity, alleviated itch and pain, and facilitated the healing of the wounds that were present at baseline [19,20].…”

Section: Introductionmentioning

confidence: 91%

“…For the day-17 and day-35 new wounds, the following outcome parameters were calculated, as applicable: healing ratio, defined as the percentage of wounds that had healed until each of the subsequent visits; median time to wound closure; and proportion of durably healed wounds, defined as the percentage of closed wounds that remained closed over a period that exceeded the typical time to recurrence, determined in natural-history studies on RDEB as about 3 weeks on average [24] (in the present analysis at least 7 weeks). Where possible, the results were compared to the corresponding, previously published results for the wounds that were present at baseline [20]. Descriptive statistics were employed to summarize the data of this post-hoc analysis.…”

Section: Calculationsmentioning

confidence: 99%

Kinetics of Wound Development and Healing Suggests a Skin-Stabilizing Effect of Allogeneic ABCB5+ Mesenchymal Stromal Cell Treatment in Recessive Dystrophic Epidermolysis Bullosa

Niebergall-Roth

Dieter

Daniele

et al. 2023

Cells

Self Cite

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Recessive dystrophic epidermolysis (RDEB) is a rare, inherited, and currently incurable skin blistering disorder characterized by cyclically recurring wounds coexisting with chronic non-healing wounds. In a recent clinical trial, three intravenous infusions of skin-derived ABCB5+ mesenchymal stromal cells (MSCs) to 14 patients with RDEB improved the healing of wounds that were present at baseline. Since in RDEB even minor mechanical forces perpetually provoke the development of new or recurrent wounds, a post-hoc analysis of patient photographs was performed to specifically assess the effects of ABCB5+ MSCs on new or recurrent wounds by evaluating 174 wounds that occurred after baseline. During 12 weeks of systemic treatment with ABCB5+ MSCs, the number of newly occurring wounds declined. When compared to the previously reported healing responses of the wounds present at baseline, the newly occurring wounds healed faster, and a greater portion of healed wounds remained stably closed. These data suggest a previously undescribed skin-stabilizing effect of treatment with ABCB5+ MSCs and support repeated dosing of ABCB5+ MSCs in RDEB to continuously slow the wound development and accelerate the healing of new or recurrent wounds before they become infected or progress to a chronic, difficult-to-heal stage.

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Neue Lokal- und Systemtherapien bei Epidermolysis bullosa

Prodinger,

Laimer

2024

hautnah

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ZusammenfassungEpidermolysis bullosa (EB) bezeichnet eine seltene, heterogene Gruppe von Genodermatosen, charakterisiert durch eine gesteigerte Fragilität von Haut und Schleimhaut. Mit zunehmender Aufklärung der molekularen Pathophysiologie haben sich in den letzten Jahren sämtliche lokale und systemische Therapieansätze in klinischen Studien etabliert. Ein bedeutender Meilenstein ist die Zulassung der FDA für die topische Gentherapie Beremagene Geperpavec (B-VEC) zur Behandlung chronischer Wunden bei dystropher EB mit Mutationen im COL7A1-Gen. Diese Therapie basiert auf modifizierten HSV-1-Vektoren, um funktionales COL7A1 in die Hautzellen zu übertagen. In einer Phase-3-Studie zeigten sich etwa drei Viertel der chronischen Wunden nach 3 Monaten komplett verschlossen, im Vergleich zu 20 % in der Placebogruppe. Klinische Studien mit RNA-basierten Therapien, wie medikamentös induzierte PTC-Readthrough und zellbasierten Therapien wie ABCB5+ mesenchymale Stammzellen zeigen Potenzial für weiteren Einsatz. Durch das 2022 speziell für EB zugelassene Filsuvez® Gel (Oleogel S‑10, Chiesi, Wien) und das topische Vitamin-D-Analogon Calcipotriol kann die Wundheilung verbessert werden, während TGF-β-Inhibitoren, z. B. Losartan, die EB-assoziierte Fibrose adressieren. Biologika wie Dupilumab, JAK- und mTOR-Inhibitoren erweitern das therapeutische Armamentarium. Immuntherapien gelten aktuell als First-line-Therapie für aggressive EB assoziierte Plattenepithelkarzinome und werden neben Multikinase-Inhibitoren (Rigosertib) in Studien untersucht. Zukünftig könnten auch MikroRNA sowohl in der Frühdiagnostik als auch topisch zur Reduktion der Tumoraggressivität eingesetzt werden. Insgesamt markieren diese Entwicklungen einen bedeutsamen Fortschritt in der therapeutischen Landschaft von EB und vermitteln Hoffnung für Betroffene und Angehörige.

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

Cited by 9 publications

References 39 publications

Skin-Derived ABCB5+ Mesenchymal Stem Cells for High-Medical-Need Inflammatory Diseases: From Discovery to Entering Clinical Routine

Skin-Derived ABCB5+ Mesenchymal Stem Cells for High-Medical-Need Inflammatory Diseases: From Discovery to Entering Clinical Routine

Kinetics of Wound Development and Healing Suggests a Skin-Stabilizing Effect of Allogeneic ABCB5+ Mesenchymal Stromal Cell Treatment in Recessive Dystrophic Epidermolysis Bullosa

Neue Lokal- und Systemtherapien bei Epidermolysis bullosa

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