Gene therapy in tissue-engineered blood vessels.
Cardiovascular disease is the leading cause of morbidity and mortality in Western society. More than 1 million arterial bypass procedures are performed annually in the United States, where either autologous veins or synthetic grafts are used to replace arteries in the coronary or peripheral circulation. Tissue engineering of blood vessels from autologous cells has the potential to produce biological grafts for use in bypass surgery. Ex vivo development of vascular grafts also provides an ideal target of site-specific gene therapy to optimize the physiology of the developing conduit, and for the possible delivery of other therapeutic genes to a vascular bed of interest. In this article, we demonstrate that by using a novel retroviral gene delivery system, a target gene of interest can be specifically delivered to the endothelial cells of a developing engineered vessel. Further, we demonstrate that this technique results in stable incorporation of the delivered gene into the target endothelial cells for more than 30 days. These data demonstrate the utility of the retroviral gene delivery approach for optimizing the biologic phenotype of engineered vessels. This also provides the framework for testing an array of genes that may improve the function of engineered blood vessels after surgical implantation.
Fields
Ryan C
RC
Department of Surgery and Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Solan
Amy
A
McDonagh
Kevin T
KT
Niklason
Laura E
LE
Lawson
Jeffrey H
JH
D016475:3T3 Cells; D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000502:physiology* / Q000637:transplantation / Q000821:virology*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D015918:Infusion Pumps, Implantable; D051379:Mice; D012190:Retroviridae / Q000235:genetics*; D013552:Swine; D023822:Tissue Engineering / Q000379:methods*; D014162:Transfection / Q000379:methods*; D019737:Transplants