Evidence map›Paper›PMID 35024388›Full record

ArticleRegenerative therapy2022

Establishment of large canine hepatocyte spheroids by mixing vascular endothelial cells and canine adipose-derived mesenchymal stem cells.

Akito Ichikawa, Sakurako Neo, Ryouhei Nukui, Yoko Yamada, Suguru Nitta, Hidetoshi Iwaki, Yusuke Yanagi, Koichi Nakayama, Shoichi Sato, Satoko Tateishi and 1 more

Open access · goldAbstract read
In one paragraph

Article in Regenerative therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.1field-weighted citation impact, top 51% 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

5 citing papers in PubMed, 7 citations in OpenAlex.

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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

11 authors at 5 institutions in 1 country.

Akito IchikawaLaboratory of Small Animal Internal Medicine, School of Veterinary Medicine, Azabu University, Sagamihara City, Kanagawa, Japan.
Sakurako NeoLaboratory of Clinical Diagnostics, School of Veterinary Medicine, Azabu University, Sagamihara City, Kanagawa, Japan.
Ryouhei NukuiLaboratory of Small Animal Internal Medicine, School of Veterinary Medicine, Azabu University, Sagamihara City, Kanagawa, Japan.
Yoko YamadaLaboratory of Small Animal Internal Medicine, School of Veterinary Medicine, Azabu University, Sagamihara City, Kanagawa, Japan.
Suguru NittaLaboratory of Small Animal Internal Medicine, School of Veterinary Medicine, Azabu University, Sagamihara City, Kanagawa, Japan.
Hidetoshi IwakiFUJIFILM Holdings, Tokyo, Japan.
Yusuke YanagiDepartment of Pediatric Surgery, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.
Koichi NakayamaDepartment of Regenerative Medicine and Biomedical Engineering, Faculty of Medicine, Saga University, Saga, Japan.
Shoichi SatoDepartment of Medical Tecnology and Sciences, School of Health Sciences at Narita, International University of Health and Welfare, Narita, Chiba, Tokyo, Japan.
Satoko TateishiZENOAQ, Koriyama City, Fukushima, Japan.
Masaharu HisasueLaboratory of Small Animal Internal Medicine, School of Veterinary Medicine, Azabu University, Sagamihara City, Kanagawa, Japan.
Azabu University · JPFujifilm (Japan) · JPInternational University of Health and Welfare · JPKyushu University · JPSaga University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionDifferentiation of hepatocytes and culture methods have been investigated in dogs as a tool to establish liver transplant and drug metabolism examination systems. However, mass culture techniques for canine hepatocytes (cHep) have not been investigated, and it is necessary to construct a suitable culture system. Recently, a protocol called Bud production has attracted attention, and a mixed culture of human and mouse hepatocytes, stem cells, and artificial blood vessels significantly improved the size and formation ratio of spheroids. The purpose of this study was to investigate and improve the in vitro culture of cHep by mixing canine adipose-derived mesenchymal stem cells (cASCs) and human umbilical vein endothelial cells (HUVECs).

methodsSpheroid formation ratio and histological examination were evaluated among four culture methods, including cHep alone, two-mix (cHep + cASCs and cHep + HUVEC), and three-mix (cHep + HUVEC + cASCs), on days 0, 4, and 7. Expression levels of liver-related genes (

resultsThe ratio of spheroid formation was 60.2% in the three-mix culture and was significantly improved compared with cHep alone (5.9%) and two-mix; cHep + cASCs (36.2%) and cHep + HUVEC (26.4%) (P < 0.001). Histological evaluation revealed that the three-mix spheroids formed large canine hepatocyte spheroids (LcHS), and hepatocytes were distributed in the center of the spheroids. Quantitative gene expression analysis of LcHS showed that liver-related genes expression were maintained the same levels with that of a culture of cHep alone from days 4-7.

conclusionThese results revealed that the three-mix culture method using cHep, HUVECs, and cASCs was capable of promoting LcHS without impairing liver function in cHep, suggesting that LcHS could be used for the application of high-volume culture techniques in dogs.

Indexed as

3D, three-dimensionsAFP, α-fetoproteinALB, albuminCaninecASC, canine adipose-derived mesenchymal stem cellsCD, cluster of differentiationCDH1, cadherin-1 (epithelital-cadherin)cHep, canine primary-cultured hepatocytesCYP, cytochromeDILI, drug induced liver injuryEGM, endothelial cell growth mediumFBS, fetal bovine serumHepatocytehFGF, human fibroblast growth factorHGM, hepatocyte growth mediumHTM, hepatocyte thawing mediumHUVEC, human umbilical vein endothelial cellsiPSC, induced pluripotent stem cellsLcHS, large canine hepatocyte spheroidsMesenchymal stem cellsMSCGM, mesenchymal stem cell growth mediumPBS, phosphate-buffered salinerf-HGF, recombinant ferine hepatocyte growth factorSF-HGM, hepatocyte growth medium for spheroid formationSpheroidsTAT, tyrosine aminotransferaseThree-dimensionsα1-AT, α1-antitrypsin

Identifiers

PMID35024388
PMCPMC8728312
OpenAlexW4200244216

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.