title: Innovations in preclinical biology: ex vivo engineering of a human kidney tissue microperfusion system.
abstract: Kidney disease is a public health problem that affects more than 20 million people in the US adult population, yet little is understood about the impact of kidney disease on drug disposition. Consequently there is a critical need to be able to model the human kidney and other organ systems, to improve our understanding of drug efficacy, safety, and toxicity, especially during drug development. The kidneys in general, and the proximal tubule specifically, play a central role in the elimination of xenobiotics. With recent advances in molecular investigation, considerable information has been gathered regarding the substrate profiles of the individual transporters expressed in the proximal tubule. However, we have little knowledge of how these transporters coupled with intracellular enzymes and influenced by metabolic pathways form an efficient secretory and reabsorptive mechanism in the renal tubule. Proximal tubular secretion and reabsorption of xenobiotics is critically dependent on interactions with peritubular capillaries and the interstitium. We plan to robustly model the human kidney tubule interstitium, utilizing an ex vivo three-dimensional modular microphysiological system with human kidney-derived cells. The microphysiological system should accurately reflect human physiology, be usable to predict renal handling of xenobiotics, and should assess mechanisms of kidney injury, and the biological response to injury, from endogenous and exogenous intoxicants.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Kelly
authors.forename: Zhican
authors.initials: Z
authors.lastname: Wang
authors.forename: Jenna L
authors.initials: JL
authors.lastname: Voellinger
authors.forename: Cathy K
authors.initials: CK
authors.lastname: Yeung
authors.forename: Danny D
authors.initials: DD
authors.lastname: Shen
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Thummel
authors.forename: Ying
authors.initials: Y
authors.lastname: Zheng
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ligresti
authors.forename: David L
authors.initials: DL
authors.lastname: Eaton
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Muczynski
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Duffield
authors.forename: Thomas
authors.initials: T
authors.lastname: Neumann
authors.forename: Anna
authors.initials: A
authors.lastname: Tourovskaia
authors.forename: Mark
authors.initials: M
authors.lastname: Fauver
authors.forename: Greg
authors.initials: G
authors.lastname: Kramer
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Asp
authors.forename: Jonathan
authors.initials: J
authors.lastname: Himmelfarb
mesh_terms: D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007684:Kidney Tubules / Q000166:cytology*; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation / Q000379:methods; D020286:Pericytes / Q000166:cytology / Q000187:drug effects; D015262:Xenobiotics / Q000633:toxicity
chemical_list: D015262:Xenobiotics