CDI is developing iCell® Hepatocytes, human hepatocytes derived from iPS cells. iCell Hepatocytes will provide, for the first time, 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 will 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 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 currently shipped as fresh cells, which remain viable and functional for at least 3 weeks following plating on collagen-coated plates. Thus, these cells can be used for acute and longer-term assays for targeted drug discovery, toxicity testing, and other life science research.
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| Cell Type | Hepatocytes | |
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| Item Number | Units per Vial | |
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| Catalog # | HCC-100-010-001-PC HCC-100-010-005-PC |
1 5 |
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| Organism | Human | |
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| Source | Differentiated from a CDI reprogrammed human iPS cell line | |
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| Quantity | >35M plateable cells / unit (1 unit = five 96-well plates) | |
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| Shipped | Fresh | |
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| Growth Properties | Adherent | |
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| Media | See iCell Hepatocytes Prototype User’s Guide in the Literature tab for media requirements. | |
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Human Cells |
iCell Hepatocytes are terminally differentiated from human iPS cells and exhibit hepatocyte characteristics and functions. |
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Homogenous and Reproducible |
iCell Hepatocytes are >95% pure, providing biologically relevant and reproducible results. |
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Functionally Stable |
iCell Hepatocytes are platable and maintain hepatocyte functions in culture for at least one weeky. |
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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. |
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iCell Heptatocytes are amenable to a variety of biochemical and cellular assays:
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.).
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.).
Request a quote online or contact Cellular Dynamics:
+1 (608) 310-5100 | US toll-free (877) 310-6688
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| Item Number | Units per Vial | |
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| Catalog # | HCC-100-010-001-PC HCC-100-010-005-PC |
1 5 |
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Technical Support |
Call +1 (608) 310-5100 | US toll-free (877) 310-6688 or submit your technical question online. |
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Reference Materials
Technology Overview
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Datasheet |
iCell Hepatocytes |
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Presentations |
Induced Pluripotent Stem Cell-derived Tissues and their Role in Developing Novel Assays for Drug Discovery
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Advanced Assays for In Vitro Toxicity Evaluation and Phenotypic Screening |
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Human iPS Cell Technology in Predictive and Mechanism-based Drug Discovery and Toxicity Testing Using Photometric-Based Assays |
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Posters |
Application of Human iPS Cell-derived Models for Highly Predictive Toxicity Screening |
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In Vitro Assessment of Drug Induced Liver Injury (DILI) Using a High Content Cellular Imaging System |
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Characterization and Function of iPSC derived Hepatocytes for Use in Toxicity
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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 |
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Predictive High-Content/High-Throughput Assays for Hepatotoxicity Using Induced Pluripotent Stem Cell (iPSC)-derived Hepatocytes |
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Applications Development at CDI: Improving Workflows, Pushing Biology, and Enabling Screening |
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| Human iPSC-derived Cells for Modelling Cellular Bioenergetics: Building a Metabolic Profile Using the XF Mito Stress Test |
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Advancements in the Use of iPS Cell-derived Systems for In Vitro Disease Modeling and Phenotypic Screening |
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Implementation of Human iPSC-derived Cell Types Into High Throughput Screening Workflows |
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Datasheet |
Cellular Dynamics International: True Human Biology in a Dish |
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Poster |
Reprogramming Human Peripheral Blood Cells |
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Bibliography |
Published Research |
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