Next Article in Journal
Cellular Repair of DNA–DNA Cross-Links Induced by 1,2,3,4-Diepoxybutane
Next Article in Special Issue
Application of Extrusion-Based Hydrogel Bioprinting for Cartilage Tissue Engineering
Previous Article in Journal
[18F]-Fluorinated Carboplatin and [111In]-Liposome for Image-Guided Drug Delivery
Previous Article in Special Issue
Effects of 3D-Printed Polycaprolactone/β-Tricalcium Phosphate Membranes on Guided Bone Regeneration
Article Menu
Issue 5 (May) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2017, 18(5), 1085; doi:10.3390/ijms18051085

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

1
Nano3D Biosciences, Houston, TX 77030, USA
2
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)
View Full-Text   |   Download PDF [3136 KB, uploaded 18 May 2017]   |  

Abstract

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
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

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.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top