Injection of genetically engineered fibroblasts corrects regenerated human epidermolysis bullosa skin tissue
Susana Ortiz-Urda, Qun Lin, Cheryl L. Green, Douglas R. Keene, M. Peter Marinkovich, Paul A. Khavari
Susana Ortiz-Urda, Qun Lin, Cheryl L. Green, Douglas R. Keene, M. Peter Marinkovich, Paul A. Khavari
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Article Dermatology

Injection of genetically engineered fibroblasts corrects regenerated human epidermolysis bullosa skin tissue

Abstract

Current therapeutic strategies for genetic skin disorders rely on the complex process of grafting genetically engineered tissue to recipient wound beds. Because fibroblasts synthesize and secrete extracellular matrix, we explored their utility in recessive dystrophic epidermolysis bullosa (RDEB), a blistering disease due to defective extracellular type VII collagen. Intradermal injection of RDEB fibroblasts overexpressing type VII collagen into intact RDEB skin stably restored correctly localized type VII collagen expression in vivo and normalized hallmark RDEB disease features, including subepidermal blistering and anchoring fibril defects.

Authors

Susana Ortiz-Urda, Qun Lin, Cheryl L. Green, Douglas R. Keene, M. Peter Marinkovich, Paul A. Khavari

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Fibroblast-mediated type VII collagen delivery to human RDEB skin. (a) T...
Fibroblast-mediated type VII collagen delivery to human RDEB skin. (a) Type VII collagen (green, first column) is shown in human RDEB skin regenerated on immune-deficient mice after intradermal injection with the cell types noted at left. Note the lack of type VII collagen in skin injected with RDEB– fibroblasts (top row) and its BMZ localization in skin injected with RDEB+ fibroblasts (middle row; arrows in dermis denote a collection of intradermal RDEB+ cells). Note the blistering seen past the border of human type VII collagen protein (bottom row). The human origin of the skin tissue studied was confirmed using species-specific antibodies to involucrin (orange, second column); triple-stained specimens with serial histological sections are shown. Scale bar: 50 μm. (b) RDEB+ fibroblasts in RDEB skin tissue. Note type VII collagen–positive dermal cells (arrows) with typical elongated fibroblast morphology in tissue injected with RDEB+ cells and the complete absence of detectable type VII collagen in RDEB skin tissue injected with RDEB– cells. Scale bars: top panels, 75 μm; bottom panels, 15 μm. E, epidermis; D, dermis; bl, blister.