Intravenously Injected Human Fibroblasts Home to Skin Wounds, Deliver Type VII Collagen, and Promote Wound Healing.

摘要

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.Molecular Therapy (2007) 15, 628-635. doi:10.1038/sj.mt.6300041; published online 23 January 2007.