Intravenous injection of Muse cells as a potential therapeutic approach for epidermolysis bullosa

Epidermolysis bullosa (EB) is a congenital and refractory blistering skin disease. Few definitive treatments have been established. In the manuscript, we show the potential of Multilineage-differentiating stress-enduring (Muse) cells for the novel treatment against EB using model mice. Muse cells, collectable as pluripotent marker SSEA-3(+), are able to develop into three germ layers and can differentiate into skin components including keratinocytes, fibroblasts and melanocytes. In this study, systemically administered human Muse cells preferentially engrafted into injured skin in type XVII collagen (Col17)-knockout EB model mice without an immunosuppressant. Of note, the spontaneous differentiation of engrafted Muse cells into keratinocytes, hair follicle cells, vascular endothelial cells and sebaceous gland cells, as well as the expression of human type VII collagen (COL7) and COL17, were observed. We also investigated CL2020, a newly-developed cell-based product for Muse cell preparation, for the treatment of EB. CL2020-treated adult Col17-knockout mice exhibited human COL7 and COL17 expression in re-epithelialized skin, and showed more moderate clinical manifestations than vehicle-treated mice showed