Evidence map›Paper›PMID 30525075›Full record

ArticleRegenerative therapy2018

Hepatic cell sheets engineered from human mesenchymal stem cells with a single small molecule compound IC-2 ameliorate acute liver injury in mice.

Noriko Itaba, Ikuya Noda, Hiroyuki Oka, Yohei Kono, Kaori Okinaka, Tsuyoshi Yokobata, Shizuma Okazaki, Minoru Morimoto, Goshi Shiota

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Regenerative therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.2field-weighted citation impact, top 20% 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

9 citing papers in PubMed, 16 citations in OpenAlex.

  1. Cell Sheet Technology as a Platform for Functional Regeneration.International journal of molecular sciences · 2026
    Review
  2. Single-cell Technology in Stem Cell Research.Current stem cell research & therapy · 2025
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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

9 authors at 1 institution in 1 country.

Noriko ItabaDivision of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan.
Ikuya NodaDivision of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan.
Hiroyuki OkaResearch Initiative Center, Tottori University, 4-101 Koyama, Tottori 680-8550, Japan.
Yohei KonoDivision of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan.
Kaori OkinakaDivision of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan.
Tsuyoshi YokobataDivision of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan.
Shizuma OkazakiDivision of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan.
Minoru MorimotoResearch Initiative Center, Tottori University, 4-101 Koyama, Tottori 680-8550, Japan.
Goshi ShiotaDivision of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan.
Tottori University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionWe previously reported that transplantation of hepatic cell sheets from human bone marrow-derived mesenchymal stem cells (BM-MSCs) with hexachlorophene, a Wnt/β-catenin signaling inhibitor, ameliorated acute liver injury. In a further previous report, we identified IC-2, a newly synthesized derivative of the Wnt/β-catenin signaling inhibitor ICG-001, as a potent inducer of hepatic differentiation of BM-MSCs.

methodsWe manufactured hepatic cell sheets by engineering from human BM-MSCs using the single small molecule IC-2. The therapeutic potential of IC-2-induced hepatic cell sheets was assessed by transplantation of IC-2- and hexachlorophene-treated hepatic cell sheets using a mouse model of acute liver injury.

resultsSignificant improvement of liver injury was elicited by the IC-2-treated hepatic cell sheets. The expression of complement C3 was enhanced by IC-2, followed by prominent hepatocyte proliferation stimulated through the activation of NF-κB and its downstream molecule STAT-3. Indeed, IC-2 also enhanced the expression of amphiregulin, resulting in the activation of the EGFR pathway and further stimulation of hepatocyte proliferation. As another important therapeutic mechanism, we revealed prominent reduction of oxidative stress mediated through upregulation of the thioredoxin (TRX) system by IC-2-treated hepatic cell sheets. The effects mediated by IC-2-treated sheets were superior compared with those mediated by hexachlorophene-treated sheets.

conclusionThe single compound IC-2 induced hepatic cell sheets that possess potent regeneration capacity and ameliorate acute liver injury.

Indexed as

8-OHdG, 8-hydroxydeoxyguanosineA1AT, α1-antitrypsinAcute liver failureALT, alanine aminotransferaseAPOE, apolipoprotein EAREG, amphiregulinAST, aspartate aminotransferaseBM-MSCs, bone marrow-derived mesenchymal stem cellsC3, complement C3C4A, complement C4AC5aR, complement C5a receptorCBP, CREB-binding proteinCCl4, carbon tetrachlorideChoREs, carbohydrate response elementsChREBP, Carbohydrate-responsive element-binding proteinCP, ceruloplasminDMSO, dimethyl sulfoxideEGFR, epidermal growth factor receptorERK, extracellular signal-regulated kinaseGPX, glutathione peroxidaseGR, Glutathione reductaseGRX, glutaredoxinGSH, glutathioneHB-EGF, heparin binding-epidermal growth factor-like growth factorHepatic cell sheetshGAPDH, human glyceraldehyde 3-phosphate dehydrogenaseHGFR, hepatocyte growth factor receptorIL-1ra, interleukin-1 receptor antagonistIL-6, interleukin-6Liver regenerationLXR, liver X receptormActb, mouse actin, betaMDA, malondialdehydeMesenchymal stem cellsNF-κB, nuclear factor-kappa BPCNA, proliferating cell nuclear antigenPRX, peroxiredoxinRBP4, retinol binding protein 4SOD, superoxide dismutaseSTAT-3, Signal Tranducer and Activator of Transcription 3TF, transferrinTGFα, transforming growth factor alphaTNFα, tumor necrosis factor alphaTRXR, thioredoxin reductaseTRX, thioredoxinWnt/β-catenin signal inhibitor

Identifiers

PMID30525075
PMCPMC6222293
OpenAlexW2888325397

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.