title: Potential of fibroblast cell therapy for recessive dystrophic epidermolysis bullosa.
abstract: 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.
authors.affiliation: The Guy's, King's College and St Thomas' School of Medicine, Genetic Skin Disease Group, St John's Institute of Dermatology, Division of Genetics and Molecular Medicine, London, UK.
authors.forename: Tracy
authors.initials: T
authors.lastname: Wong
authors.forename: Luke
authors.initials: L
authors.lastname: Gammon
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.forename: Jemima E
authors.initials: JE
authors.lastname: Mellerio
authors.forename: Patricia J C
authors.initials: PJ
authors.lastname: Dopping-Hepenstal
authors.forename: John
authors.initials: J
authors.lastname: Pacy
authors.forename: George
authors.initials: G
authors.lastname: Elia
authors.forename: Rosemary
authors.initials: R
authors.lastname: Jeffery
authors.forename: Irene M
authors.initials: IM
authors.lastname: Leigh
authors.forename: Harshad
authors.initials: H
authors.lastname: Navsaria
authors.forename: John A
authors.initials: JA
authors.lastname: McGrath
mesh_terms: D001706:Biopsy; D002448:Cell Adhesion / Q000502:physiology; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002478:Cells, Cultured; D024143:Collagen Type VII / Q000235:genetics / Q000378:metabolism; D016108:Epidermolysis Bullosa Dystrophica / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D006801:Humans; D007271:Injections, Intradermal; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D012155:Reticulin / Q000378:metabolism / Q000648:ultrastructure; D012867:Skin / Q000378:metabolism / Q000473:pathology; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D024143:Collagen Type VII; D012333:RNA, Messenger; D012155:Reticulin