Evidence map›Paper›PMID 22885101›Full record

ArticleStem cell research2012

Hepatocyte-like cells differentiated from human induced pluripotent stem cells: relevance to cellular therapies.

Yue Yu, Hongling Liu, Yasuhiro Ikeda, Bruce P Amiot, Piero Rinaldo, Stephen A Duncan, Scott L Nyberg

Open access · greenAbstract read
In one paragraph

Article in Stem cell research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed
3.1field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

66 citing papers in PubMed, 106 citations in OpenAlex.

  1. A CYP3A7 metabolically competent human induced pluripotent stem cell-derived hepatocyte-like cell (hHLCDrug metabolism and disposition: the biological fate of chemicals · 2026
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  15. TNFα induces mitochondrial fragmentation and biogenesis in human airway smooth muscle.American journal of physiology. Lung cellular and molecular physiology · 2021
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6 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Yue YuDivision of Experimental Surgery, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Hongling Liu
Yasuhiro Ikeda
Bruce P Amiot
Piero Rinaldo
Stephen A Duncan
Scott L Nyberg
Mayo Clinic · USMedical College of Wisconsin · US

Funding

PILOT AND FEASIBILTY PROGRAMP30DK084567 · NIDDK · MAYO CLINIC ROCHESTER · PI GREGORY J. GORES · 2009 to 2026
$22.2M
NIDDK NIH HHS P30 DK084567NIDDK NIH HHS P30DK084567
6 · The paper itself

Abstract

unlabelledMaturation of induced pluripotent stem cells (hiPSCs) to hepatocyte-like cells (HLCs) has been proposed to address the shortage of human hepatocytes for therapeutic applications. The purpose of this study was to evaluate hiPSCs, HLCs and hepatocytes, all of human origin, in terms of performance metrics of relevance to cell therapies. hiPSCs were differentiated to HLCs in vitro using an established four-stage approach. We observed that hiPSCs had low oxygen consumption and possessed small, immature mitochondria located around the nucleus. With maturation to HLCs, mitochondria showed characteristic changes in morphology, ultrastructure, and gene expression. These changes in mitochondria included elongated morphology, swollen cristae, dense matrices, cytoplasmic migration, increased expression of mitochondrial DNA transcription and replication-related genes, and increased oxygen consumption. Following differentiation, HLCs expressed characteristic hepatocyte proteins including albumin and hepatocyte nuclear factor 4-alpha, and intrinsic functions including cytochrome P450 metabolism. But HLCs also expressed high levels of alpha fetoprotein, suggesting a persistent immature phenotype or inability to turn off early stage genes. Furthermore, the levels of albumin production, urea production, cytochrome P450 activity, and mitochondrial function of HLCs were significantly lower than primary human hepatocytes.

conclusion- hiPSCs offer an unlimited source of human HLCs. However, reduced functionality of HLCs compared to primary human hepatocytes limits their usefulness in clinical practice. Novel techniques are needed to complete differentiation of hiPSCs to mature hepatocytes.

Indexed as

Cell DifferentiationCell- and Tissue-Based TherapyCells, CulturedCytochrome P-450 Enzyme SystemHepatocyte Nuclear Factor 4HepatocytesHumansInduced Pluripotent Stem CellsCytochrome P-450 Enzyme SystemHepatocyte Nuclear Factor 4

Identifiers

PMID22885101
PMCPMC3619384
OpenAlexW2020886306

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.