Possible Therapeutic Application of Adipose-Derived Stem Cells for the Treatment of Recessive Dystrophic Epidermolysis Bullosa

Abstract

　The epidermis, a rapidly regenerating tissue, acts as a barrier against environmental factors. The dermis, composed of connective tissue, imparts strength and flexibility to the skin. Full-thickness skin defects are healed by the migration of epidermal stem cells from regions surrounding the ulcer, and by wound contraction induced by the myofibroblasts in the dermis. Stem cells are expected to play a central role in treating skin diseases as well as in the diseases of other organs. Among stem cells, adipose-derived stem cells (ADSCs) can be easily harvested in large quantities, have less immunogenicity, and a powerful immunosuppressive potential. Therefore, they are suitable for clinical use, including allogeneic cell transplantation. ADSCs promote wound healing and can differentiate into keratinocyte-like cells. Recessive dystrophic epidermolysis bullosa (RDEB) is a severe form of epidermolysis bullosa. The pathogenesis of RDEB involves mutations in the COL7A1 gene, which encodes type VII collagen, the main constituent of anchoring fibrils that attach the epidermis to the dermis. Persistent skin erosion frequently results in intractable ulcers, which result in severe scarring. Therefore, skin ulcers in RDEB patients should be treated at an early stage. Keratinocyte-like cells transdifferentiated from ADSCs (KC-ADSCs) express more type VII collagen than undifferentiated ADSCs do, thereby facilitating skin wound healing with less contracture. Therefore, KC-ADSCs may be useful for the treatment of skin ulcers in RDEB and other skin diseases.