Efficacy of human living skin equivalent in the treatment of inherited epidermolysis bullosa

Abstract

Background. Inherited epidermolysis bullosa is a group of genetic skin disorders caused by mutations in genes encoding structural proteins of epidermis and dermo-epidermal junction. Clinical manifestations are characterized by spontaneous or trauma-induced skin and/or mucosal blistering, and extensive wounds. The use of tissue-engineered skin substitutes composed of allogeneic human skin cells is considered to be a perspective therapeutic approach in improving wound healing process. Aims. To assess safety and efficacy of human skin equivalent in the treatment of inherited epidermolysis bullosa patients Methods. 7 patients (5 female and 2 male subjects) from the age of 20 to 55 with inherited epidermolysis bullosa with different clinical subtypes were enrolled in the study: 3 patients with intermediate recessive dystrophic epidermolysis bullosa, 2 patients with severe recessive dystrophic epidermolysis bullosa, 1 patient with dominant dystrophic epidermolysis bullosa and 1 patient with junctional epidermolysis bullosa. Transplantation of composite allogeneic living skin equivalent comprising allogeneic keratinocytes and fibroblasts in low concentration (5 mg/ml) embedded within a type I collagen gel matrix was performed. The living skin equivalent was developed at N.K. Koltsov Institute of Developmental Biology. 19 erosions and ulcers with a surface area between 0.4 and 120 cm2 were evaluated. At day 14 clinical assessment was performed. To assess level of expression immunofluorescence antigen mapping was used. Results. At day 14 complete erosion closure was achieved in 10 (53%) erosions. 4 (21%) erosions reduced in size 75%. Size reduction between 25 and 75% was shown in a single (5%) case, no clinical efficacy was demonstrated in 4 (21%) cases. Collagen VII expression increased comparing to baseline level and accompanied clinical improvement. Conclusions. The obtained data showed clinical efficacy of topical treatment with living skin equivalent, although no statistically significant difference was seen between living skin equivalent and atraumatic non-adhesive dressings.