IN VITRO KIDNEY CELL CULTURE FOR NEPHROTOXIN ASSAYS

RENAL ISCHEMIA AND POISONING OF THE KIDNEY TUBULES BY TOXIC AGENTS ARE MAJOR CAUSES OF TUBULAR NECROSIS AND ACUTE RENAL FAILURE. UNDERSTNADING THE MECHANISM OF ACTION OF DRUGS AND CHEMICALS ON RENAL CELLS IS IMPORTANT IN TOXICOLOGICAL SCREENING OF DRUGS AS WELL AS THE DEVELOPMENT CLINICAL TREATMENTS. THE GOAL OF OUR PHASE I RESEARCH PROGRAM 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-CULTURES FOR TOXICOLOGICAL TESTING AND NECHANISTIC STUDIES. THE DEFINED SUBSTRATES WILL BE BASED ON COLLAGEN-GLYCOSAMINOGLYCAN CROSSLINKED COPOLYMERS. TWO ANIMAL SPECIES WILL BE STUDIED: RABBIT AND RAT; 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 OF THIS STUDY ARE CULTURES SUFFICIENTLY STABLE IN DIFFERENTIATED PROPERTIES TO BE SHIPPABLE TO THE CUSTOMER'S LABORATORY AS KITS FOR USE IN DRUG SCREENING ASSAYS, AND THE VALIDATION OF CELL CULTURE AND ASSAY SYSTEMS FOR THE ABILITY TO PREDICT HUMAN NEPHROTOXICITY.