Kerstan Andreas, Dieter Kathrin, Niebergall-Roth Elke, Dachtler Ann-Kathrin, Kraft Korinna, Stücker Markus, Daeschlein Georg, Jünger Michael, Görge Tobias, Meyer-Pannwitt Ulrich, Erfurt-Berge Cornelia, von Engelhardt Charlotte, Klare Andreas, Pfeiffer Christiane, Esterlechner Jasmina, Schröder Hannes M, Gasser Martin, Waaga-Gasser Ana M, Goebeler Matthias, Ballikaya Seda, Sadeghi Samar, Murphy George F, Orgill Dennis P, Frank Natasha Y, Ganss Christoph, Scharffetter-Kochanek Karin, Frank Markus H, Kluth Mark A
Department of Dermatology, Venereology, and Allergology, University Hospital Würzburg, Würzburg, Germany.
RHEACELL GmbH & Co. KG, Heidelberg, Germany.
JID Innov. 2022 Jan;2(1). doi: 10.1016/j.xjidi.2021.100067. Epub 2021 Oct 25.
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 allogeneic ABCB5 MSCs/cm 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.
尽管遵循了指南规范的标准治疗方案，但仍有相当数量的慢性静脉溃疡（CVU）无法愈合。皮肤来源的ABCB5间充质干细胞（MSC）可以抑制慢性伤口中由白细胞介素-1β持续驱动的炎症。基于其在小鼠CVU模型中的促伤口愈合作用以及一项自体的首次人体研究，ABCB5 MSC已成为难治性CVU基于细胞的先进治疗的潜在候选者。在本项介入性、多中心、单臂、I/IIa期临床试验中，CVU对标准治疗耐药的受试者除接受标准治疗外，还在每平方厘米伤口面积上接受一或两次局部应用1×10的异体ABCB5 MSC。在83例治疗中出现的不良事件中，只有3例被判定与细胞产品有关；它们为轻度或中度，且未留下后遗症而康复。从基线到第12周伤口大小显著减小，全分析集（N = 31）的伤口大小中位数减少76%，符合方案集（N = 27）减少78%，应答者亚组（n = 21）减少87%。总之，该研究治疗耐受性良好且安全。该治疗在12周内使伤口大小显著减小，确定ABCB5 MSC为否则无法治愈的CVU辅助治疗的潜在候选者。这些结果证明有必要开展一项更大规模的随机对照试验以确认临床疗效。
