Evidence map›Paper›PMID 35294680›Full record

ArticleJournal of gastroenterology2022

Successful induction of human chemically induced liver progenitors with small molecules from damaged liver.

Takayuki Miyoshi, Masaaki Hidaka, Daisuke Miyamoto, Yusuke Sakai, Shunsuke Murakami, Yu Huang, Takanobu Hara, Akihiko Soyama, Kengo Kanetaka, Takahiro Ochiya and 1 more

Abstract read
PubMed Publisher
In one paragraph

Article in Journal of gastroenterology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.5field-weighted citation impact, top 10% 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

13 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. Review
  3. Bioengineered Bile Duct for Liver Regenerative Medicine and Bile Duct Reconstruction.JGH open : an open access journal of gastroenterology and hepatology · 2025
    Review
  4. Cell therapy for liver disorders: past, present and future.Nature reviews. Gastroenterology & hepatology · 2025
    Review
  5. Review
  6. Review
  7. Article
  8. Review
  9. Article
  10. Update on Hepatobiliary Plasticity.Seminars in liver disease · 2023
    Article
  11. Article
  12. Article
  13. Article
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

11 authors at 4 institutions in 1 country.

Takayuki MiyoshiDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, 852-8501, Japan.
Masaaki HidakaDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, 852-8501, Japan.
Daisuke MiyamotoDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, 852-8501, Japan.
Yusuke SakaiDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, 852-8501, Japan.
Shunsuke MurakamiDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, 852-8501, Japan.
Yu HuangDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, 852-8501, Japan.
Takanobu HaraDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, 852-8501, Japan.
Akihiko SoyamaDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, 852-8501, Japan.
Kengo KanetakaDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, 852-8501, Japan.
Takahiro OchiyaDepartment of Molecular Cell Therapy Research, Medical Research Institute, Tokyo Medical University, Tokyo, Japan.
Susumu EguchiDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, 852-8501, Japan. sueguchi@nagasaki-u.ac.jp.ORCID 0000-0001-8191-6405
Nagasaki University · JPKyushu University · JPTokyo Medical University · JPUniversity of Nagasaki · JP

Funding

the Japan Agency for Medical Research and Development 20bm0404042h0002
6 · The paper itself

Abstract

backgroundHuman chemically induced liver progenitors (hCLiP) induced by small molecules produced by mature hepatocytes can potentially overcome issues related to hepatocyte transplantation, such as graft rejection or donor shortage. However, to our knowledge, no studies have explored the induction of hCLiP from mature hepatocytes (MHs) in damaged liver, indicated for liver transplantation.

methodsLiver tissues were collected from surgically resected livers, including damaged livers, of 86 patients at our department, and hepatocytes were isolated using the collagenase perfusion method. Hepatocytes isolated from 33 of these 86 donors were cultured in YAC medium containing Y-27632 (ROCK inhibitor), A-83-01 (TGF-β type I receptor inhibitor), and CHIR99021 (GSK-3 inhibitor) to induce hCLiP, and their functions were assessed.

resultsHepatocytes were isolated regardless of the liver fibrosis classifications (viability: F0,1: 87.2 ± 13.2%; F2,3: 87.8 ± 13.1%; and F4: 86.3 ± 4.2%). Most hepatocytes cultured in the YAC medium acquired the liver progenitor cell (LPC) gene. The expression of MH markers (ALB, HNF4α, G6PC, and CYP1A2) was lower in hCLiP than in MHs before reprogramming. Reverse transcription-polymerase chain reaction revealed that hCLiP markers (e.g., EpCAM, SOX9, CK19, and CD133) exhibited higher expression in LPCs than in MHs. Furthermore, hCLiPs had the ability to differentiate into hepatocytes, and were engrafted on the liver surface as mature hepatocytes.

conclusionHepatocytes could be isolated from damaged liver. Furthermore, hCLiP may be obtained from hepatocytes isolated from damaged liver and may differentiate into MHs in vitro. Autologous hCLiP can potentially be transplanted without tumorigenesis and remodel damaged liver.

Indexed as

Glycogen Synthase Kinase 3LiverCell DifferentiationCell ProliferationCells, CulturedHepatocytesHumansGlycogen Synthase Kinase 3hCLiPHepatocyte isolationLiver cirrhosisProgenitor cellSmall molecule

Identifiers

PMID35294680
OpenAlexW4220917630

What OpenQuestion holds

Textmetadata
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.