1. ¹Department of Pathology and Laboratory Medicine, University of Wisconsin–Madison, Madison, Wisconsin, USA
2. ²Stratatech Corporation, Madison, Wisconsin, USA
3. ³Department of Surgery and Cell Biology, Neurobiology and Anatomy, Loyola University Medical Center, Maywood, Illinois, USA
4. ⁴School of Pharmacy and Department of Chemistry, University of Wisconsin–Madison, Madison, Wisconsin, USA
5. ⁵Program in Cellular and Molecular Biology, University of Wisconsin–Madison, Madison, Wisconsin, USA
6. ⁶Medical Scientist Training Program, University of Wisconsin School of Medicine and Public Health, University of Wisconsin–Madison, Madison, Wisconsin, USA

Correspondence: B. Lynn Allen-Hoffmann, Department of Pathology and Laboratory Medicine, University of Wisconsin–Madison, 5605 Medical Sciences Center, 1300 University Avenue, Madison, Wisconsin 53706-1102, USA. E-mail: blallenh@wisc.edu

The first two authors contributed equally to this work.

Received 4 April 2008; Accepted 25 November 2008; Published online 3 February 2009.

Abstract

When skin is compromised, a cascade of signals initiates the rapid repair of the epidermis to prevent fluid loss and provide defense against invading microbes. During this response, keratinocytes produce host defense peptides (HDPs) that have antimicrobial activity against a diverse set of pathogens. Using nonviral vectors we have genetically modified the novel, nontumorigenic, pathogen-free human keratinocyte progenitor cell line (NIKS) to express the human cathelicidin HDP in a tissue-specific manner. NIKS skin tissue that expresses elevated levels of cathelicidin possesses key histological features of normal epidermis and displays enhanced antimicrobial activity against bacteria in vitro. Moreover, in an in vivo infected burn wound model, this tissue results in a two log reduction in a clinical isolate of multidrug-resistant Acinetobacter baumannii. Taken together, these results suggest that this genetically engineered human tissue could be applied to burns and ulcers to counteract bacterial contamination and prevent infection.