[HTML][HTML] Potential of fibroblast cell therapy for recessive dystrophic epidermolysis bullosa

T Wong, L Gammon, L Liu, JE Mellerio… - Journal of Investigative …, 2008 - Elsevier
T Wong, L Gammon, L Liu, JE Mellerio, PJC Dopping-Hepenstal, J Pacy, G Elia, R Jeffery…
Journal of Investigative Dermatology, 2008Elsevier
Recessive dystrophic epidermolysis bullosa (RDEB) is a severe inherited skin-blistering
disorder caused by mutations in the COL7A1 gene that lead to reduced type-VII collagen
and defective anchoring fibrils at the dermal–epidermal junction (DEJ). Presently there are
no effective treatments for this disorder. Recent mouse studies have shown that intradermal
injections of normal human fibroblasts can generate new human type-VII collagen and
anchoring fibrils at the DEJ. To assess potential clinical benefits in humans, we gave single …
Recessive dystrophic epidermolysis bullosa (RDEB) is a severe inherited skin-blistering disorder caused by mutations in the COL7A1 gene that lead to reduced type-VII collagen and defective anchoring fibrils at the dermal–epidermal junction (DEJ). Presently there are no effective treatments for this disorder. Recent mouse studies have shown that intradermal injections of normal human fibroblasts can generate new human type-VII collagen and anchoring fibrils at the DEJ. To assess potential clinical benefits in humans, we gave single intradermal injections of allogeneic fibroblasts to five subjects with RDEB. We noted increased type-VII collagen at the DEJ at 2 weeks and at 3 months following injection and increased anchoring fibrils, although none of these had normal morphology. No adverse effects, clinical or immunopathologic, were noted. We believe the major effect of allogeneic fibroblasts is to increase the recipients’ own COL7A1 mRNA levels with greater deposition of mutant type-VII collagen at the DEJ and formation of additional rudimentary anchoring fibrils. Nevertheless, this mutant protein may be partially functional and capable of increasing adhesion at the DEJ. This is the first study demonstrating that intradermal injections of allogeneic fibroblasts have therapeutic potential in human subjects with RDEB. JID JOURNAL CLUB ARTICLE: For questions, answers, and open discussion about this article please go to http://network.nature.com/group/jidclub
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