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Related Experiment Video

Updated: May 21, 2026

Using Human Induced Pluripotent Stem Cell-derived Hepatocyte-like Cells for Drug Discovery
12:40

Using Human Induced Pluripotent Stem Cell-derived Hepatocyte-like Cells for Drug Discovery

Published on: May 19, 2018

Improving hepatic metabolic function with 3D iPSC-derived human hepatocytes.

Victoria Pozo Garcia1, Mostafa Kiamehr2, Robin Versteegden1

  • 1Department of Chemistry and Pharmaceutical Sciences, Amsterdam Institute of Molecular and Life Sciences (AIMMS), Vrije Universiteit (VU) Amsterdam, De Boelelaan 1108, 1081 HZ, Amsterdam, the Netherlands.

Cell Biology and Toxicology
|May 20, 2026
PubMed
Summary

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Organobodies: a robust and size-controllable system for generating scalable hiPSC-derived liver organoids for drug toxicity screening.

Biofabrication·2026

Three-dimensional hepatocyte-like cells (3D HLCs) derived from human induced pluripotent stem cells (iPSCs) show enhanced liver function and drug metabolism. These 3D HLCs more accurately model drug-induced liver injury, improving drug discovery and personalized medicine.

Area of Science:

  • Biotechnology
  • Stem Cell Biology
  • Drug Discovery

Background:

  • Human induced pluripotent stem cells (iPSCs) offer potential for drug discovery and personalized medicine.
  • Three-dimensional (3D) cell culture, using scaffolds like synthetic polypeptide hydrogels, enhances cell function and mimics in vivo environments.
  • Hepatic spheroids and organoids promote liver maturation and function.

Purpose of the Study:

  • To differentiate 3D hepatocyte-like cells (3D HLCs) from human iPSCs using a synthetic polypeptide hydrogel.
  • To functionally characterize these 3D HLCs for metabolic capacity and drug metabolism.
  • To compare the hepatic maturation and drug-induced liver injury (DILI) response of 3D HLCs with conventional 2D cultures and primary hepatocytes.

Main Methods:

  • Differentiation of human iPSCs into 3D HLCs using a synthetic polypeptide hydrogel scaffold.
Keywords:
3D spheroidDILILiverMetabolismOrganobodiesiPSCs

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Last Updated: May 21, 2026

Using Human Induced Pluripotent Stem Cell-derived Hepatocyte-like Cells for Drug Discovery
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Using Human Induced Pluripotent Stem Cell-derived Hepatocyte-like Cells for Drug Discovery

Published on: May 19, 2018

Serum Free Production of Three-dimensional Human Hepatospheres from Pluripotent Stem Cells
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Serum Free Production of Three-dimensional Human Hepatospheres from Pluripotent Stem Cells

Published on: July 20, 2019

  • Assessment of metabolic capacity via LC-MS semi-targeted metabolomics, focusing on drug biotransformation and mitochondrial function.
  • Evaluation of CYP450 enzyme activity (CYP3A4, CYP2D6) and response to eight DILI compounds in 2D and 3D HLCs, compared to 2D primary human hepatocytes (2D PHHs).

    • Main Results:

    • 3D HLCs exhibited a more mature hepatic phenotype compared to 2D cultures, acquiring xenobiotic metabolism capacity earlier (day 30 vs. day 40).
    • Significantly increased CYP3A4 (>20-fold) and CYP2D6 (2-11-fold) activity was observed in 3D HLCs.
    • 3D HLCs demonstrated enhanced mitochondrial function, including higher β-oxidation, and showed cytotoxic responses to DILI compounds that more closely resembled 2D PHHs than 2D HLCs.

    Conclusions:

    • 3D HLCs derived from iPSCs represent a promising in vitro model for drug metabolism and toxicology studies.
    • The enhanced hepatic function and DILI modeling capabilities of 3D HLCs hold potential for personalized drug testing and disease modeling.
    • Synthetic hydrogel scaffolds facilitate the development of functional 3D liver models from iPSCs.