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Injection of genetically engineered fibroblasts corrects regenerated human epidermolysis bullosa skin tissue
Susana Ortiz-Urda, … , M. Peter Marinkovich, Paul A. Khavari
Susana Ortiz-Urda, … , M. Peter Marinkovich, Paul A. Khavari
Published January 15, 2003
Citation Information: J Clin Invest. 2003;111(2):251-255. https://doi.org/10.1172/JCI17193.
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Article Dermatology

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

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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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Figure 2

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Intradermal injection of RDEB+ fibroblasts delivers human type VII colla...
Intradermal injection of RDEB+ fibroblasts delivers human type VII collagen to the murine epidermal-dermal junction. Skin from mice injected intradermally with the fibroblast types noted at the left of each row of panels was stained with either the NP185 human-specific monoclonal antibody to type VII collagen (red, first column) or rabbit polyclonal antibodies recognizing both mouse and human type VII collagen (green, second column). Note the presence of human type VII collagen at the cutaneous BMZ in skin injected with RDEB+ fibroblasts (top row). Note the lack of BMZ-localized type VII collagen in skin injected with normal fibroblasts (middle row) and its complete absence in skin injected with RDEB– fibroblasts (bottom row). Circular structures in the mid to deep dermis are hair follicles; note perifollicular dermal human type VII collagen in dermis injected with RDEB+ fibroblasts and with the normal fibroblasts (middle row). Merged inset (×40) showing skin injected with RDEB+ fibroblasts (top row, far right panel) demonstrates the junction of human type VII collagen detection in the BMZ. Dotted lines denote the upper papillary dermis below the BMZ. Scale bar: 50 μm.
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