Evidence map›Paper›PMID 34772451›Full record

ArticleStem cell research & therapy2021

Efficient hepatic differentiation and regeneration potential under xeno-free conditions using mass-producible amnion-derived mesenchymal stem cells.

Jiwan Choi, Seoon Kang, Bitnara Kim, Seongjun So, Jongsuk Han, Gyeong-Nam Kim, Mi-Young Lee, Seonae Roh, Ji-Yoon Lee, Soo Jin Oh and 4 more

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

Article in Stem cell research & therapy, 2021. 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, 15 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

14 authors at 2 institutions in 1 country.

Jiwan ChoiDepartment of Medical Science, Asan Medical Institute of Convergence Science and Technology (AMIST), University of Ulsan College of Medicine, Asan Medical Center, Seoul, 05505, South Korea.
Seoon KangDepartment of Medical Science, Asan Medical Institute of Convergence Science and Technology (AMIST), University of Ulsan College of Medicine, Asan Medical Center, Seoul, 05505, South Korea.
Bitnara KimStem Cell Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul, 05505, South Korea.
Seongjun SoDepartment of Medical Science, Asan Medical Institute of Convergence Science and Technology (AMIST), University of Ulsan College of Medicine, Asan Medical Center, Seoul, 05505, South Korea.
Jongsuk HanDepartment of Medical Science, Asan Medical Institute of Convergence Science and Technology (AMIST), University of Ulsan College of Medicine, Asan Medical Center, Seoul, 05505, South Korea.
Gyeong-Nam KimDepartment of Medical Science, Asan Medical Institute of Convergence Science and Technology (AMIST), University of Ulsan College of Medicine, Asan Medical Center, Seoul, 05505, South Korea.
Mi-Young LeeDepartment of Obstetrics and Gynecology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 05505, South Korea.
Seonae RohStem Cell Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul, 05505, South Korea.
Ji-Yoon LeeAsan Institute for Life Sciences, Asan Medical Center and Department of Convergence Medicine, College of Medicine, University of Ulsan, Seoul, 05505, South Korea.
Soo Jin OhAsan Institute for Life Sciences, Asan Medical Center and Department of Convergence Medicine, College of Medicine, University of Ulsan, Seoul, 05505, South Korea.
Young Hoon SungDepartment of Medical Science, Asan Medical Institute of Convergence Science and Technology (AMIST), University of Ulsan College of Medicine, Asan Medical Center, Seoul, 05505, South Korea.
Yeonmi LeeStem Cell Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul, 05505, South Korea.
Sung Hoon KimDepartment of Obstetrics and Gynecology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 05505, South Korea. kimsung@amc.seoul.kr.
Eunju KangDepartment of Medical Science, Asan Medical Institute of Convergence Science and Technology (AMIST), University of Ulsan College of Medicine, Asan Medical Center, Seoul, 05505, South Korea. ekang@cha.ac.kr.ORCID 0000-0002-7240-7868
Ulsan College · KRAsan Medical Center · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAmnion-derived mesenchymal stem cells (AM-MSCs) are an attractive source of stem cell therapy for patients with irreversible liver disease. However, there are obstacles to their use due to low efficiency and xeno-contamination for hepatic differentiation.

methodsWe established an efficient protocol for differentiating AM-MSCs into hepatic progenitor cells (HPCs) by analyzing transcriptome-sequencing data. Furthermore, to generate the xeno-free conditioned differentiation protocol, we replaced fetal bovine serum (FBS) with polyvinyl alcohol (PVA). We investigated the hepatocyte functions with the expression of mRNA and protein, secretion of albumin, and activity of CYP3A4. Finally, to test the transplantable potential of HPCs, we transferred AM-MSCs along with hepatic progenitors after differentiated days 11, 12, and 13 based on the expression of hepatocyte-related genes and mitochondrial function. Further, we established a mouse model of acute liver failure using a thioacetamide (TAA) and cyclophosphamide monohydrate (CTX) and transplanted AM-HPCs in the mouse model through splenic injection.

resultsWe analyzed gene expression from RNA sequencing data in AM-MSCs and detected downregulation of hepatic development-associated genes including GATA6, KIT, AFP, c-MET, FGF2, EGF, and c-JUN, and upregulation of GSK3. Based on this result, we established an efficient hepatic differentiation protocol using the GSK3 inhibitor, CHIR99021. Replacing FBS with PVA resulted in improved differentiation ability, such as upregulation of hepatic maturation markers. The differentiated hepatocyte-like cells (HLCs) not only synthesized and secreted albumin, but also metabolized drugs by the CYP3A4 enzyme. The best time for translation of AM-HPCs was 12 days from the start of differentiation. When the AM-HPCs were transplanted into the liver failure mouse model, they settled in the damaged livers and differentiated into hepatocytes.

conclusionThis study offers an efficient and xeno-free conditioned hepatic differentiation protocol and shows that AM-HPCs could be used as transplantable therapeutic materials. Thus, we suggest that AM-MSC-derived HPCs are promising cells for treating liver disease.

Indexed as

AmnionMesenchymal Stem CellsAnimalsCell DifferentiationGlycogen Synthase Kinase 3HepatocytesHumansLiverMiceGlycogen Synthase Kinase 3Amnion-derived mesenchymal stem cellsDifferentiationGSK3 inhibitorHepatic progenitorPolyvinyl alcoholXeno-free

Identifiers

PMID34772451
PMCPMC8588618
OpenAlexW3214339653

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.