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

Andreas KerstanKathrin DieterElke Niebergall-RothAnn-Kathrin DachtlerKorinna KraftMarkus StückerGeorg DaeschleinMichael JüngerTobias GoergeUlrich Meyer-PannwittCornelia Erfurt-BergeCharlotte von EngelhardtAndreas KlareChristiane PfeifferJasmina EsterlechnerHannes M SchröderMartin GasserAna Maria Waaga-GasserMatthias GoebelerSeda BallikayaSamar SadeghiGeorge F MurphyDennis P OrgillNatasha Y FrankChristoph GanssKarin Scharffetter-KochanekMarkus H FrankMark Andreas Kluth
Published in: JID innovations (2021)
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.
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