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Int. J. Mol. Sci. 2017, 18(5), 1085;

Assembly of Hepatocyte Spheroids Using Magnetic 3D Cell Culture for CYP450 Inhibition/Induction

Nano3D Biosciences, Houston, TX 77030, USA
Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
Author to whom correspondence should be addressed.
Academic Editor: Mohamed N. Rahaman
Received: 9 March 2017 / Revised: 9 May 2017 / Accepted: 13 May 2017 / Published: 18 May 2017
(This article belongs to the Special Issue Three-dimensional (3D) Bioprinting of Tissues and Organs)
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There is a significant need for in vitro methods to study drug-induced liver injury that are rapid, reproducible, and scalable for existing high-throughput systems. However, traditional monolayer and suspension cultures of hepatocytes are difficult to handle and risk the loss of phenotype. Generally, three-dimensional (3D) cell culture platforms help recapitulate native liver tissue phenotype, but suffer from technical limitations for high-throughput screening, including scalability, speed, and handling. Here, we developed a novel assay for cytochrome P450 (CYP450) induction/inhibition using magnetic 3D cell culture that overcomes the limitations of other platforms by aggregating magnetized cells with magnetic forces. With this platform, spheroids can be rapidly assembled and easily handled, while replicating native liver function. We assembled spheroids of primary human hepatocytes in a 384-well format and maintained this culture over five days, including a 72 h induction period with known CYP450 inducers/inhibitors. CYP450 activity and viability in the spheroids were assessed and compared in parallel with monolayers. CYP450 activity was induced/inhibited in spheroids as expected, separate from any toxic response. Spheroids showed a significantly higher baseline level of CYP450 activity and induction over monolayers. Positive staining in spheroids for albumin and multidrug resistance-associated protein (MRP2) indicates the preservation of hepatocyte function within spheroids. The study presents a proof-of-concept for the use of magnetic 3D cell culture for the assembly and handling of novel hepatic tissue models. View Full-Text
Keywords: hepatocyte; liver; metabolomics; in vitro methods; high-throughput hepatocyte; liver; metabolomics; in vitro methods; high-throughput

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Desai, P.K.; Tseng, H.; Souza, G.R. Assembly of Hepatocyte Spheroids Using Magnetic 3D Cell Culture for CYP450 Inhibition/Induction. Int. J. Mol. Sci. 2017, 18, 1085.

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