Renal ischemia and poisoning of the kidney tubules by toxic agents are major causes of tubular necrosis and acute renal failure. Understanding the action mechanisms of drugs and chemicals on renal cells is important in the toxicological screening of drugs as well as the development clinical treatments. The goal of Phase I is to determine the feasibility of using membranes synthesized from extracellular matrix components to improve the growth and differentiated characteristics of kidney cell cultures, and to evaluate suitability of these cultures for toxicological testing and mechanistic studies. The defined substrates will be based on collagen-glycosaminoglycan crosslinked copolymers. Two animal species, rabbit and rat, will be studied, and work will be extended to human cells in Phase II. Successful results will lead to increased longevity and differentiation, permitting better standardization of cultures, longer contact times for agents to be tested, and greater sensitivity and range in observing toxic endpoints. The long-term objectives are cultures sufficiently stable in differentiated properties to be shipped to customer laboratories as kits for use in drug screening assays, and the validation of cell culture and assay systems for the ability to predict human nephrotoxicity.Awardee's statement of the potential commercial applications of the research:For toxicology or hormone assays, our system can be commercialized either as a service, or as test kits including cells, matrix materials and serum-free medium. The substrates in the form of membranes or culture wells may also be commercialized for differentiated cell culture applications. The in vitro assays should reduce the need to use animals in nephrotoxin screening assays.National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
