ArticlePloS one2019
Liver biopsy derived induced pluripotent stem cells provide unlimited supply for the generation of hepatocyte-like cells.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.
- A comprehensive transcriptomic comparison of hepatocyte model systems improves selection of models for experimental use.Communications biology · 2022Pooled it
- Developments and Applications of Liver-on-a-Chip Technology-Current Status and Future Prospects.Biomedicines · 2025Review
- Liver organoids: updates on generation strategies and biomedical applications.Stem cell research & therapy · 2024Review
- iPSC-derived cells for whole liver bioengineering.Frontiers in bioengineering and biotechnology · 2024Review
- Arouse potential stemness: Intrinsic and acquired stem cell therapeutic strategies for advanced liver diseases.Cell insight · 2023Review
- Organoids to model liver disease.JHEP reports : innovation in hepatology · 2021Review
- Induction and Maturation of Hepatocyte-Like CellsFrontiers in cell and developmental biology · 2021Review
- Human Three-Dimensional Hepatic Models: Cell Type Variety and Corresponding Applications.Frontiers in bioengineering and biotechnology · 2021Review
- Review
- Practical choice for robust and efficient differentiation of human pluripotent stem cells.World journal of stem cells · 2020Review
- Evolving Cell-Based and Cell-Free Clinical Strategies for Treating Severe Human Liver Diseases.Cells · 2020Review
- Current Perspective: 3D Spheroid Models Utilizing Human-Based Cells for Investigating Metabolism-Dependent Drug-Induced Liver Injury.Frontiers in medical technology · 2020Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsHepatocyte-like cells (HLCs) differentiated from induced pluripotent stem cells (iPSCs) have emerged as a promising cell culture model to study metabolism, biotransformation, viral infections and inherited liver diseases. iPSCs provide an unlimited supply for the generation of HLCs, but incomplete HLC differentiation remains a major challenge. iPSC may carry-on a tissue of origin dependent expression memory influencing iPSC differentiation into different cell types. Whether liver derived iPSCs (Li-iPSCs) would allow the generation of more fully differentiated HLCs is not known.
methodsIn the current study, we used primary liver cells (PLCs) expanded from liver needle biopsies and reprogrammed them into Li-iPSCs using a non-integrative Sendai virus-based system. Li-iPSCs were differentiated into HLCs using established differentiation protocols. The HLC phenotype was characterized at the protein, functional and transcriptional level. RNA sequencing data were generated from the originating liver biopsies, the Li-iPSCs, fibroblast derived iPSCs, and differentiated HLCs, and used to characterize and compare their transcriptome profiles.
resultsLi-iPSCs indeed retain a liver specific transcriptional footprint. Li-iPSCs can be propagated to provide an unlimited supply of cells for differentiation into Li-HLCs. Similar to HLCs derived from fibroblasts, Li-HLCs could not be fully differentiated into hepatocytes. Relative to the originating liver, Li-HLCs showed lower expression of liver specific transcription factors and increased expression of genes involved in the differentiation of other tissues.
conclusionsPLCs and Li-iPSCs obtained from small pieces of human needle liver biopsies constitute a novel unlimited source for the production of HLCs. Despite the preservation of a liver specific gene expression footprint in Li-iPSCs, the generation of fully differentiated hepatocytes cannot be achieved with the current differentiation protocols.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.