ADENOVIRUS-BASED TRANSIENT EXPRESSION SYSTEMS FOR PERITONEAL MEMBRANE RESEARCH

Scientific Affairs, 1 Renal Division, Baxter Healthcare Corporation, McGaw Park, Illinois, USA; Department of Medicine, 2 McMaster University and Division of Nephrology, St. Joseph's Hospital, Hamilton, Ontario, Canada Correspondence to: C.M. Hoff, Baxter Healthcare Corporation, Renal Division, 1620 Waukegan Road, MPGR-A2N, McGaw Park, Illinois, 60085 USA. Cathy_Hoff{at}baxter.com Background: Peritoneal membrane research has provided important insights into the physiology and pathophysiology of this tissue that is of vital importance for peritoneal dialysis patients. Among the various tools and methodologies used to study the peritoneum, we have extensively used adenovirus-mediated gene transfer. Methods: A literature review was carried out. Information from reviewed papers was combined with the authors' experience and results. Results: We have used first-generation adenoviruses that are simple to construct and can infect a wide range of dividing and nondividing cell types. These vectors are restricted, however, in that they provide only a short duration of transgene expression and may elicit an inflammatory response. Modifications to this technology with helper-dependent adenovirus may circumvent these problems but with increased complexity of construction. Adenovirus-mediated gene transfer has been used to evaluate the effect of several cytokines and growth factors on peritoneal membrane physiology. We have used intraperitoneal delivery of transforming growth factor-ß to generate an experimental model system of resolving peritoneal fibrosis and epithelial mesenchymal transdifferentiation. We have studied the effects of the inflammatory cytokines interleukin-1ß and tumor necrosis factor alpha on the peritoneum, and have shown that antiangiogenic factors such as sFLT-1 and angiostatin can reduce the damaging effects of exposure to peritoneal dialysis solutions in an animal model. Conclusions: The use of recombinant adenoviruses to genetically modify cells and tissues is now a common laboratory research tool. This technique has provided important advances in our understanding of the peritoneal membrane. KEY WORDS: Adenovirus; gene transfer; peritoneal membrane; peritoneal fibrosis; TGF-ß1; proinflammatory cytokines. Received 24 January 2006; accepted 6 June 2006.