Enrichment of high-functioning human iPS cell-derived hepatocyte-like cells for pharmaceutical research

Enrichment of high-functioning human iPS cell-derived hepatocyte-like cells for pharmaceutical... Human iPS cell-derived hepatocyte-like cells are expected to be utilized in pharmaceutical research. However, the purity of high-functioning hepatocyte-like cells is not high enough. In particular, the purity of cytochrome P450 3A4 (CYP3A4), which is a representative hepatic drug-metabolizing enzyme, positive cells is still quite low (approximately 20%). To address this problem, we established the CYP3A4-NeoR-EGFP transgenic reporter human iPS cell line (CYP3A4-NeoR-EGFP iPS cells) by using genome editing technology. The CYP3A4-NeoR-EGFP iPS cells were differentiated into hepatocyte-like cells, and then the hepatocyte-like cells were treated with neomycin to concentrate the hepatocyte-like cells which strongly express CYP3A4. After the neomycin treatment, the percentage of CYP3A4-positive cells was higher than 80%. The gene expression levels of various drug-metabolizing enzymes, transporters, and hepatic transcription factors were significantly enhanced by neomycin treatment. In addition, the CYP1A2, 2C19, 2D6, and 3A4 activities and biliary excretion capacities were significantly increased by neomycin treatment. We also confirmed that the detection sensitivity of drug-inducing hepatotoxicity was enhanced by neomycin treatment. We succeeded in obtaining human iPS cell-derived hepatocyte-like cells that highly express CYP3A4 at high purity. We believe that our high-purity and high-functioning hepatocyte-like cells could be used to evaluate the risk of drug candidates. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Biomaterials Elsevier

Enrichment of high-functioning human iPS cell-derived hepatocyte-like cells for pharmaceutical research

Loading next page...
 
/lp/elsevier/enrichment-of-high-functioning-human-ips-cell-derived-hepatocyte-like-vvzG90R4Hj
Publisher
Elsevier
Copyright
Copyright © 2018 Elsevier Ltd
ISSN
0142-9612
D.O.I.
10.1016/j.biomaterials.2018.01.019
Publisher site
See Article on Publisher Site

Abstract

Human iPS cell-derived hepatocyte-like cells are expected to be utilized in pharmaceutical research. However, the purity of high-functioning hepatocyte-like cells is not high enough. In particular, the purity of cytochrome P450 3A4 (CYP3A4), which is a representative hepatic drug-metabolizing enzyme, positive cells is still quite low (approximately 20%). To address this problem, we established the CYP3A4-NeoR-EGFP transgenic reporter human iPS cell line (CYP3A4-NeoR-EGFP iPS cells) by using genome editing technology. The CYP3A4-NeoR-EGFP iPS cells were differentiated into hepatocyte-like cells, and then the hepatocyte-like cells were treated with neomycin to concentrate the hepatocyte-like cells which strongly express CYP3A4. After the neomycin treatment, the percentage of CYP3A4-positive cells was higher than 80%. The gene expression levels of various drug-metabolizing enzymes, transporters, and hepatic transcription factors were significantly enhanced by neomycin treatment. In addition, the CYP1A2, 2C19, 2D6, and 3A4 activities and biliary excretion capacities were significantly increased by neomycin treatment. We also confirmed that the detection sensitivity of drug-inducing hepatotoxicity was enhanced by neomycin treatment. We succeeded in obtaining human iPS cell-derived hepatocyte-like cells that highly express CYP3A4 at high purity. We believe that our high-purity and high-functioning hepatocyte-like cells could be used to evaluate the risk of drug candidates.

Journal

BiomaterialsElsevier

Published: Apr 1, 2018

References

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create lists to
organize your research

Export lists, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off