Treatment of Hereditary Epidermolysis Bullosa: Updates and Future Prospects

Chao-Kai Hsu; Sheng-Pei Wang; Julia Yu-Yun Lee; John A. McGrath


Am J Clin Dermatol. 2014;15(1):1-6. 

In This Article

4 Intradermal Injection of Allogeneic Fibroblasts

Wong et al.[17] reported the first clinical trial of intradermal injection of allogeneic fibroblasts in patients with RDEB. No clinical or immunopathologic adverse effects were observed in the study. Increased C7 expression at the dermal–epidermal junction was noted at 2 weeks and 3 months following a single injection. Although the donor fibroblasts were undetectable 2 weeks after injection, clinicopathologic benefits were sustained for several months. Of note, most patients with low baseline C7 showed limited response to the allogeneic fibroblasts. These observations suggested that the major effect of allogeneic fibroblast injection is to increase the recipient's own COL7A1 mRNA levels, leading to greater deposition of mutant C7 at the basement membrane zone. Nagy et al.[18] found that heparin binding–EGF-like growth factor (HB-EGF) is elevated in the skin after fibroblast injection and that this can increase COL7A1 gene expression in normal and RDEB keratinocytes and fibroblasts in vitro, thus providing one explanation for how allogeneic fibroblasts might improve skin function in RDEB. Other murine studies have indicated that a direct release of C7 protein from the injected allogeneic fibroblasts might also contribute to the clinicopathologic response.[19,20] Whether HB-EGF, or other growth factors such as EGF itself, can be directly applied to the wounds of RDEB patients is still under pre-clinical investigation. Two clinical trials comparing allogeneic fibroblasts versus vehicle in wound healing in RDEB have been reported recently. One study found no difference between fibroblasts or vehicle in wound healing responses,[21] but another trial showed that a single injection of allogeneic fibroblasts can accelerate wound healing in RDEB for 28 days compared with vehicle alone.[22] Injecting fibroblasts into patient skin can be painful and therefore further studies on the mode of cell delivery, as well as additional optimization of the frequency of fibroblast injections and the amount of cells per injection, will be necessary to define the clinical utility of allogeneic fibroblast cell therapy in the overall management of RDEB (Fig. 2).