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

Andreas Kerstan, Kathrin Dieter, Elke Niebergall-Roth, Ann-Kathrin Dachtler, Korinna Kraft, Markus Stücker, Georg Daeschlein, Michael Jünger, Tobias Görge, Ulrich Meyer-Pannwitt, Cornelia Erfurt-Berge, Charlotte von Engelhardt, Andreas Klare, Christiane Pfeiffer, Jasmina Esterlechner, Hannes M Schröder, Martin Gasser, Ana M Waaga-Gasser, Matthias Goebeler, Seda Ballikaya, Samar Sadeghi, George F Murphy, Dennis P Orgill, Natasha Y Frank, Christoph Ganss, Karin Scharffetter-Kochanek, Markus H Frank, Mark A Kluth

JID innovations 2022 Jan

filter terms:

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 1×106 allogeneic ABCB5+ MSCs/cm2 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.

Citation

PMID: 34870260

View Full Text