iCell Cardiomyocytes

iCell® Hepatocytes

iCell HepatocytesiCell® Hepatocytes, human hepatocytes derived from iPS cells. provide access to commercial quantities of high quality, high purity human liver cells for preclinical drug discovery, hepatotoxicity testing, and disease research. Liver toxicity and alterations of hepatic physiology are frequently occurring reasons for preclinical failure during drug development. In addition, drug-induced liver injury is the most common reason for market withdrawal of approved drugs due to safety concerns. Liver diseases associated with drug toxicity can be attributed, in large part, to the lack of biologically relevant and predictive model systems. Current hepatocyte model systems include primary human hepatocytes harvested from cadavers, immortalized cell lines, and animal models. However, each of these model systems presents limitations in functionality, reproducibility, and/or availability. iCell Hepatocytes overcome these limitations and provide a reliable source of well-characterized, highly reproducible, and readily available human hepatocytes for preclinical drug development and safety testing.


iCell Hepatocytes

iCell Hepatocytes Show Characteristic Morphology
iCell Hepatocytes exhibit cobblestone morphology, round nuclei with distinct nucleoli, bi-nucleation (ovals), and formation of bile canaliculi (arrows).

Specifications

iCell Hepatocytes are a highly pure population of human hepatocytes derived from induced pluripotent stem (iPS) cells using CDI’s proprietary differentiation and purification protocols. iCell Hepatocytes express alpha-1-antitrypsin (AAT), asialoglycoprotein receptor (ASGR1), hepatocyte nuclear factor 4 alpha (HNF4A), and secrete albumin at levels similar to adult primary human hepatocytes. In addition, the cells exhibit intrinsic metabolism (e.g. glycogen and lipid storage), xenobiotic metabolism, and transporter functions. Importantly, iCell Hepatocytes respond appropriately to known hepatotoxicants and support HCV and HBV infection.

iCell Hepatocytes are shipped cryopreserved. These cells remain viable and functional for at least 3 weeks following plating on collagen-coated plates. Thus, they can be used for acute and longer-term assays for targeted drug discovery, toxicity testing, and other life science research.

iCell Hepatocytes

iCell Hepatocytes Exhibit Hepatocyte Protein Expression and Function
iCell Hepatocytes exhibit expression of (A) alpha-1-antitrypsin,(B) albumin, (C) glycogen storage (measured by PAS staining), and lipid storage (data not shown).
Cell Type Hepatocytes  
Catalog # Item Package Size

HCC-100-010-001

iCell Hepatocytes

 

>9.0 x 106 viable cells

PHC-100-020-001-PT

iCell Hepatocytes 2.0 Kit

 

  • >9.0 x 106 viable cells
  • 3 ml Medium Supplement
Organism Human  
Source Differentiated from a CDI reprogrammed human iPS cell line
Quantity >9.0 x 106 viable cells, sufficient for one 96-well plate
Shipped Frozen  
Growth Properties Adherent
Media See iCell Hepatocytes User’s Guide in the Literature tab for media requirements.

Advantages


Human Cells

iCell Hepatocytes are terminally differentiated from human iPS cells and exhibit hepatocyte characteristics and functions.

Homogenous and Reproducible

iCell Hepatocytes are >95% pure, providing biologically relevant and reproducible results.

Functionally Stable

iCell Hepatocytes are platable and maintain hepatocyte functions in culture for at least one week.

Known Genotype

iCell Hepatocytes have been genotyped for 1,936 ADME markers in over 200 genes, including all FDA-validated genes and >90% of the ADME Core markers as defined by the PharmaADME group.

Applications

iCell Heptatocytes are amenable to a variety of biochemical and cellular assays:

  • Hepatoxicity
  • Intrinsic metabolism
  • Xenobiotic metabolism
  • Transporter function
  • Viral infectivity

iCell Hepatocytes
Figure 1: iCell Hepatocytes are Sensitive to Known Hepatotoxicants
iCell Hepatocytes exhibit concentration-dependent toxicity in response to troglitazone, terfenadine, tamoxifen, and chlorpromazine. As expected, cell viability remained unchanged in response to theophylline, and acetaminophen-induced toxicity was observed only at high concentrations. Cell viability was measured by CellTiter-Glo Cell Viability Assay (Promega Corp.).

iCell Hepatocytes
Figure 2: iCell Hepatocytes Exhibit Metabolism-Dependent Toxicity
iCell Hepatocytes exhibit concentration-dependent toxicity in response to aflatoxin-B1, which is metabolized by the liver to a toxic intermediate. A similar response is observed in primary human hepatocytes but not in HepG2 cells, which do not exhibit robust cytochrome P450 activity. Aflatoxin-B1-mediated toxicity in iCell Hepatocytes is inhibited in the presence of ketoconazole and alpha-napthoflavine, inhibitors of cytochrome P450 enzymes (data not shown). Cell viability was measured by CellTiter-GloCell Viability Assay (Promega Corp.).

To Order

Request a quote online or contact Cellular Dynamics:

+1 (608) 310-5100 | US toll-free (877) 310-6688

  Item Number Package Size
iCell Hepatocytes HCC-100-010-001 >9.0 x 106 viable cells
iCell Hepatocytes 2.0 Kit
Currently available as a prototype product
PHC-100-020-001-PT
  • >9.0 x 106 viable cells
  • 3 ml Medium Supplement

Support


Technical Support

Call +1 (608) 310-5100 | US toll-free (877) 310-6688 or submit your technical question online.

Literature

User Documentation

User's Guide: iCell Hepatocytes
Please contact Technical Support for this document

Application Protocol

Immunofluorescent Labeling
(PDF)

Safety Data Sheet

iCell Hepatocytes
HCC-100-010-001
(PDF)

Datasheet

iCell Hepatocytes
(PDF)

Application Note

Using iPSC-derived Hepatocytes as a Functional Model System for Human Hepatitis Research
(PDF)

Presentations

Induced Pluripotent Stem Cell-derived Tissues and their Role in Developing Novel Assays for Drug Discovery
(PDF, presented at AIMBE 2013)

Advanced Assays for In Vitro Toxicity Evaluation and Phenotypic Screening
(PDF, presented at SLAS2013)

Human iPS Cell Technology in Predictive and Mechanism-based Drug Discovery and Toxicity Testing Using Photometric-Based Assays
(PDF, presented at SOT Annual Meeting 2012)

Posters

Application of Human iPS Cell-derived Models for Highly Predictive Toxicity Screening
(PDF, presented at ELRIG 2013)

In Vitro Assessment of Drug Induced Liver Injury (DILI) Using a High Content Cellular Imaging System
(PDF, presented at SOT Annual Meeting 2013)

Characterization and Function of iPSC derived Hepatocytes for Use in Toxicity
(PDF, presented at SOT Annual Meeting 2013)

Comparison of Two Cell Model Systems, Primary Human Hepatocytes and hiPSC-derived Hepatocytes to Determine the Hepatoxicity of Three Candidate Drugs Developed for Rheumatoid Arthritis
(PDF, presented at SOT Annual Meeting 2012)

Predictive High-Content/High-Throughput Assays for Hepatotoxicity Using Induced Pluripotent Stem Cell (iPSC)-derived Hepatocytes
(PDF, presented at SOT 2012)

Applications Development at CDI: Improving Workflows, Pushing Biology, and Enabling Screening
(PDF, presented at the CDI User Group Meeting 2012)

Human iPSC-derived Cells for Modelling Cellular Bioenergetics: Building a Metabolic Profile Using the XF Mito Stress Test
(PDF, presented at the CDI User Group Meeting 2012)

Advancements in the Use of iPS Cell-derived Systems for In Vitro Disease Modeling and Phenotypic Screening
(PDF, presented at StemCONN 2013)

Implementation of Human iPSC-derived Cell Types Into High Throughput Screening Workflows
(PDF, presented at SLAS 2013)

Technology Overview

Cellular Dynamics International: True Human Biology in a Dish
(PDF)

Published Research
(HTML)