Journal
BIOMATERIALS
Volume 33, Issue 18, Pages 4700-4711Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2012.02.063
Keywords
Nephrotoxicity; Primary proximal tubules; 3-D culture; Organoid culture; In vivo biomarkers; In vitro toxicity assessment
Funding
- University of Utah
- National Center for Research Resources [UL1-RR025764, C06-RR11234]
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Cell cell and cell-matrix interactions control cell phenotypes and functions in vivo. Maintaining these interactions in vitro is essential to both produce and retain cultured cell fidelity to normal phenotype and function in the context of drug efficacy and toxicity screening. Two-dimensional (2-D) cultures on culture plastics rarely recapitulate any of these desired conditions. Three dimensional (3-D) culture systems provide a critical junction between traditional, yet often irrelevant, in vitro cell cultures and more accurate, yet costly, in vivo models. This study describes development of an organoid-derived 3-D culture of kidney proximal tubules (PTs) that maintains native cellular interactions in tissue context, regulating phenotypic stability of primary cells in vitro for up to 6 weeks. Furthermore, unlike immortalized cells on plastic, these 3-D organoid kidney cultures provide a more physiologically-relevant response to nephrotoxic agent exposure, with production of toxicity biomarkers found in vivo. This biomimetic primary kidney model has broad applicability to high-throughput drug and biomarker nephrotoxicity screening, as well as more mechanistic drug toxicology, pharmacology, and metabolism studies. (C) 2012 Elsevier Ltd. All rights reserved.
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