Allogeneic ABCB5 + mesenchymal stem cells for treatment-refractory chronic venous ulcers: a phase I/IIa clinical trial.

Autor:	Kerstan A; Department of Dermatology, Venereology, and Allergology, University Hospital Würzburg, Würzburg, Germany., Dieter K; RHEACELL GmbH & Co. KG, Heidelberg, Germany., Niebergall-Roth E; TICEBA GmbH, Heidelberg, Germany., Dachtler AK; RHEACELL GmbH & Co. KG, Heidelberg, Germany., Kraft K; RHEACELL GmbH & Co. KG, Heidelberg, Germany., Stücker M; Department of Dermatology, St. Josef Hospital Bochum, Ruhr University Bochum, Bochum, Germany., Daeschlein G; Department of Dermatology, University Medicine Greifswald, Greifswald, Germany., Jünger M; Department of Dermatology, University Medicine Greifswald, Greifswald, Germany., Görge T; Department of Dermatology, University Hospital Münster, Münster, Germany., Meyer-Pannwitt U; pro scientia med at the Department of Clinical Research and Development, MARE Clinic, Kiel, Germany., Erfurt-Berge C; Department of Dermatology, University Hospital Erlangen, Erlangen, Germany., von Engelhardt C; Klinische Forschung Schwerin GmbH, Schwerin, Germany., Klare A; Klinische Forschung Hamburg GmbH, Hamburg, Germany., Pfeiffer C; Department of Dermatology and Allergic Diseases, University Hospital, Ulm, Germany., Esterlechner J; TICEBA GmbH, Heidelberg, Germany., Schröder HM; RHEACELL GmbH & Co. KG, Heidelberg, Germany., Gasser M; Department of Surgery, University Hospital Würzburg, Würzburg, Germany., Waaga-Gasser AM; Department of Surgery, University Hospital Würzburg, Würzburg, Germany.; Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Goebeler M; Department of Dermatology, Venereology, and Allergology, University Hospital Würzburg, Würzburg, Germany., Ballikaya S; TICEBA GmbH, Heidelberg, Germany., Sadeghi S; TICEBA GmbH, Heidelberg, Germany., Murphy GF; Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Orgill DP; Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Frank NY; Department of Medicine, VA Boston Healthcare System, Boston, MA, USA.; Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Transplant Research Program, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.; Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA., Ganss C; RHEACELL GmbH & Co. KG, Heidelberg, Germany.; TICEBA GmbH, Heidelberg, Germany., Scharffetter-Kochanek K; Department of Dermatology and Allergic Diseases, University Hospital, Ulm, Germany., Frank MH; Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Transplant Research Program, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.; Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.; School of Medical and Health Sciences, Edith Cowan University, Perth, Western Australia, Australia., Kluth MA; RHEACELL GmbH & Co. KG, Heidelberg, Germany.; TICEBA GmbH, Heidelberg, Germany.
Jazyk:	angličtina
Zdroj:	JID innovations : skin science from molecules to population health [JID Innov] 2022 Jan; Vol. 2 (1). Date of Electronic Publication: 2021 Oct 25.
DOI:	10.1016/j.xjidi.2021.100067
Abstrakt:	A significant number of chronic venous ulcers (CVUs) fail to heal despite of guideline-conform standard of care. Skin-derived ABCB5 + mesenchymal stem cells (MSCs) can dampen the sustained IL-1β-driven inflammation present in chronic wounds. Based on their wound healing-facilitating effects in a mouse CVU model and an autologous first-in-human study, ABCB5 + MSCs have emerged as a potential candidate for cell-based advanced therapy of non-healing CVUs. In the present interventional, multicenter, single-arm, phase I/IIa clinical trial, subjects whose CVU had emerged as standard therapy-resistant received one or two topical applications of 1×10 6 allogeneic ABCB5 + MSCs/cm 2 wound area in addition to standard treatment. Out of 83 treatment-emergent adverse events, only three were judged related to the cell product; they were mild or moderate and recovered without sequelae. Wound size markedly decreased from baseline to week 12, resulting in a median wound size reduction of 76% (full analysis set, N=31), 78% (per-protocol set, N=27) and 87% (subset of responders; n=21). In conclusion, the study treatment was well tolerated and safe. The treatment elicited a profound wound size reduction within 12 weeks, identifying ABCB5 + MSCs as a potential candidate for adjunctive therapy of otherwise incurable CVUs. These results justify the conduct of a larger, randomized, controlled trial to confirm clinical efficacy. Competing Interests: CONFLICT OF INTEREST NYF and MHF are inventors or co-inventors of US and international patents assigned to Brigham and Women’s Hospital and/or Boston Children’s Hospital, Boston, MA, USA, licensed to TICEBA GmbH, Heidelberg, Germany, and RHEACELL GmbH & Co. KG, Heidelberg, Germany. MHF and KSK serve as scientific advisors to TICEBA and RHEACELL and participate in corporate-sponsored research collaborations with RHEACELL. KD, AKD, KK and HS are employees of RHEACELL. ENR, JE, SB and SS are employees of TICEBA. CG is CEO, and MAK is CSO of RHEACELL and TICEBA. The remaining authors state no conflict of interest.
Databáze:	MEDLINE
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