1. ¹Department of Dermatology, The Keck School of Medicine, University of Southern California, Los Angeles, California, USA
2. ²Department of Biochemistry and Molecular Biology, Shriners Hospital for Children, Portland, Oregon, USA

Correspondence: Mei Chen, Department of Dermatology, The USC Laboratories for Investigative Dermatology, Room 204, Cancer Research Laboratory, 1303 N Mission Road, Los Angeles, California 90033, USA. E-mail: chenm@usc.edu

Received 19 May 2006; Accepted 2 October 2006; Published online 23 January 2007.

Abstract

Patients with dystrophic epidermolysis bullosa (DEB) have incurable skin fragility, blistering, and multiple skin wounds because of mutations in the gene that encodes for type VII collagen (C7), which holds together the epidermal and dermal layers of human skin. The intradermal injection of gene-corrected DEB fibroblasts, recombinant C7 protein, or lentiviral vectors expressing C7 is a potential therapy for DEB. Nevertheless, severe DEB causes widespread wounds and treatment would require multiple injections. An alternative strategy might be to inject genetically engineered cells into the patient's circulation that home to the skin wounds and deposit the transgene product. In this study, we demonstrated that intravenously (IV) injected, molecularly engineered DEB fibroblasts (overexpressing human C7) homed to murine skin wounds and continuously delivered C7 at the wound site, where it incorporated into the skin's basement membrane zone and formed anchoring fibril structures. Wounds made on murine or grafted human skin demonstrated accelerated healing when the animals were IV injected with gene-corrected DEB fibroblasts. Our data demonstrate that abundant C7 promotes wound healing. This is also the first evidence that IV injected, molecularly engineered skin fibroblasts can deliver C7 to skin wounds. This strategy could be useful for treating DEB patients.