Surgical Treatment of Wounds Using Stem Cells in Epidermolysis Bullosa (EB)

Abstract

Epidermolysis bullosa (EB) is a group of hereditary skin diseases, or genodermatoses, characterized by the formation of severe, chronic blisters with painful and life-threatening complications. Despite the previous and ongoing progress in the field, there are still no effective causative treatments for EB. The treatment is limited to relieving symptoms, which—depending on disease severity—may involve skin (blisters, poorly healing wounds caused by the slightest mechanical stimuli, contractures, scarring, pseudosyndactyly) and internal organ abnormalities (esophageal, pyloric, or duodenal atresia; renal failure; and hematopoietic abnormalities). The last decade saw a series of important discoveries that paved the way for new treatment methods, including gene therapy, bone marrow transplantation, cell therapy (allogenic fibroblasts, mesenchymal stem cells [MSCs], and clinical use of induced pluripotent stem cells. Tissue engineering experts are attempting to develop skin-like structures that can facilitate the process of healing to promote skin reconstruction in injuries that are currently incurable. However, this is incredibly challenging, due to the complex structure and the many functions of the skin. Below, we characterize EB and present its potential treatment methods. Despite the cure for EB being still out of reach, recent data from animal models and initial clinical trials in humans have raised patients’, clinicians’, and researchers’ expectations. Consequently, modifying the course of the disease and improving the quality of life have become possible. Moreover, the conclusions drawn based on EB treatment may considerably improve the treatment of other genetic diseases.

Stem Cell Therapies for Epidermolysis Bullosa Treatment

“…Despite the progress in the field, there are still no established effective causative treatments for EB. The management of EB is primarily symptomatic and aims to prevent relapses [ 44 ]. The basic principles of care for all patients with EB are the avoidance of blisters, a protective covering of the skin, and the prevention of complications and infections, with careful wound care, facilitated by the use of sterile synthetic, non-adhesive bandages.…”

“…Despite the fact that keratinocytes represent the main cell target in EB, the discovery of the disease’s systemic nature led to the investigation of alternative cellular sources for cell therapies including HSCs and MSCs [ 45 ]. Among the most investigated cell therapies for EB are bone more transplantation (BMT) and cell therapies with allogeneic MSCs, allogenic fibroblasts and clinical use of iPSCs [ 44 , 45 ]. BM–derived cells and MSCs have certain mechanisms of action that make them an attractive candidate for EB treatment.…”

Optimization of Novel Human Acellular Dermal Dressing Sterilization for Routine Use in Clinical Practice

“…A commonly considered and established alternative is the use of acellular dermal matrices (ADMs), which meet most clinical expectations and may serve as a dressing alone or in combination with cellular therapy [1,2]. In fact, the use of acellular dermal scaffolds as stem cell carriers represents an exciting option to improve wound closure, reepithelization, and wound remodeling [1,[3][4][5].…”

“…Currently available ADMs are manufactured from human cadaveric skin, while others are prepared from xenogeneic skin fragments. Here, we present a novel approach in which abdominoplasty skin was used for ADM preparation as a part of a novel BIOOPA dressing, which was successful for epidermolysis bullosa treatment [3,5]. We evaluate the effects of different doses of radiation sterilization by high-energy electron beams on the collagen structure, free radicals' development, and cellular immune responses to novel ADM prepared from human abdominoplasty skin (BIOOPA scaffold).…”