A gene therapy approach for long-term normalization of blood pressure in hypertensive mice by ANP-secreting human skin grafts.

ABSTRACT: The use of bioengineered human skin as a bioreactor to deliver therapeutic factors has a number of advantages including accessibility that allows manipulation and monitoring of genetically modified cells. We demonstrate a skin gene therapy approach that can regulate blood pressure and treat systemic hypertension by expressing atrial natriuretic peptide (ANP), a hormone able to decrease blood pressure, in bioengineered human skin equivalents (HSE). Additionally, the expression of a selectable marker gene, multidrug resistance (MDR) type 1, is linked to ANP expression on a bicistronic vector and was coexpressed in the human keratinocytes and fibroblasts of the HSE that were grafted onto immunocompromised mice. Topical treatments of grafted HSE with the antimitotic agent colchicine select for

SUBMITTER: Therrien JP 

PROVIDER: S-EPMC2824301 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature