307 Safety and clinical effects of systemic allogeneic UCB-MSCs therapy for patients with RDEB

Abstract

Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a severe genodermatosis caused by mutations in COL7A1 and characterized by mucocutaneous blistering after minor trauma. Bone marrowemesenchymal stromal cells (MSCs) have shown therapeutic potential for RDEB patients. Recent preclinical study demonstrated that a systemic infusion of human umbilical cord blood (UCB)-derived nonhematopoietic stem cells correct RDEB murine model. In this study, we wanted to determine the safety and possible clinical efficacy of systemic allogeneic UCB-MSCs therapy for RDEB patients. Six Korean RDEB patients (4 adults and 2 children) were included in this clinical trial. Each participant received three intravenous infusions of allogeneic UCB-MSCs (1e3Â 10 6 cells/kg) with no HLA matching. Change in mean disease severity measured by Birmingham Epidermolysis Bullosa Severity Score (BEBSS) was-16 point at 60 days. Mean BEBSS total body surface area (%) was significantly reduced (-15 point) from baseline to day 60. Blister count and blister area/body surface area (%) were reduced by 50% at day 60 compared to baseline. Pain and pruritus score (VAS) were also reduced by 43% and 13% at day 60 compared to baseline. We also found the increased number of c-kit+ mast cells and CD68+ macrophages in the patient's skin at baseline, but the number of both cells were markedly reduced at day 60. No significant increase in C7 deposition was observed at day 60. There were no severe adverse events during day 180. The results suggest that administration of allogeneic UCB-MSCs in patients with RDEB is safe and provide indications of possible clinical benefits, to be confirmed in further clinical trials.