Evidence map›Paper›PMID 36231094›Full record

ArticleCells2022

Direct Differentiation of Human Embryonic Stem Cells to 3D Functional Hepatocyte-like Cells in Alginate Microencapsulation Sphere.

Xiaoling Xie, Xiaoling Zhou, Tingdang Liu, Zhiqian Zhong, Qi Zhou, Waqas Iqbal, Qingdong Xie, Chiju Wei, Xin Zhang, Thomas Ming Swi Chang and 1 more

Open access · goldAbstract read
In one paragraph

Article in Cells, 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
1.0field-weighted citation impact, top 25% 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, 12 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
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 2 institutions in 2 countries.

Xiaoling XieStem Cell Research Center, Shantou University Medical College, Shantou 515041, China.
Xiaoling ZhouStem Cell Research Center, Shantou University Medical College, Shantou 515041, China.ORCID 0000-0001-5721-944X
Tingdang LiuStem Cell Research Center, Shantou University Medical College, Shantou 515041, China.
Zhiqian ZhongStem Cell Research Center, Shantou University Medical College, Shantou 515041, China.
Qi ZhouStem Cell Research Center, Shantou University Medical College, Shantou 515041, China.
Waqas IqbalStem Cell Research Center, Shantou University Medical College, Shantou 515041, China.
Qingdong XieStem Cell Research Center, Shantou University Medical College, Shantou 515041, China.
Chiju WeiGuangdong Provincial Key Laboratory of Marine Biotechnology, Institute of Marine Sciences, Shantou University, Shantou 515063, China.
Xin ZhangLaboratory of Molecular Cardiology, First Affiliated Hospital of Shantou University Medical College, Shantou 515041, China.
Thomas Ming Swi ChangArtificial Cells & Organs Research Centre, Departments of Physiology, Medicine & Biomedical Engineering, McGill University, Montreal, QC H3G 1Y6, Canada.
Pingnan SunStem Cell Research Center, Shantou University Medical College, Shantou 515041, China.ORCID 0000-0002-3325-8062
Shantou University · CNMcGill University · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe lack of a stable source of hepatocytes is one of major limitations in hepatocyte transplantation and clinical applications of a bioartificial liver. Human embryonic stem cells (hESCs) with a high degree of self-renewal and totipotency are a potentially limitless source of a variety of cell lineages, including hepatocytes. Many techniques have been developed for effective differentiation of hESCs into functional hepatocyte-like cells. However, the application of hESC-derived hepatocyte-like cells (hESC-Heps) in the clinic has been constrained by the low yield of fully differentiated cells, small-scale culture, difficulties in harvesting, and immunologic graft rejection. To resolve these shortcomings, we developed a novel 3D differentiation system involving alginate-microencapsulated spheres to improve current hepatic differentiation, providing ready-to-use hESC-Heps.

methodsIn this study, we used alginate microencapsulation technology to differentiate human embryonic stem cells into hepatocyte-like cells (hESC-Heps). Hepatic markers of hESC-Heps were examined by qPCR and Western blotting, and hepatic functions of hESC-Heps were evaluated by indocyanine-green uptake and release, and ammonia removal.

resultsThe maturity and hepatic functions of the hESC-Heps derived from this 3D system were better than those derived from 2D culture. Hepatocyte-enriched genes, such as HNF4α, AFP, and ALB, were expressed at higher levels in 3D hESC-Heps than in 2D hESC-Heps. 3D hESC-Heps could metabolize indocyanine green and had better capacity to scavenge ammonia. In addition, the 3D sodium alginate hydrogel microspheres could block viral entry into the microspheres, and thus protect hESC-Heps in 3D microspheres from viral infection.

conclusionWe developed a novel 3D differentiation system for differentiating hESCs into hepatocyte-like cells by using alginate microcapsules.

Indexed as

Human Embryonic Stem CellsAlginatesalpha-FetoproteinsAmmoniaCapsulesEmbryonic Stem CellsHepatocytesHumansHydrogelsIndocyanine GreenAlginatesalpha-FetoproteinsAmmoniaCapsulesHydrogelsIndocyanine Green3D differentiation and cultureartificial cellshepatocyte-like cellshuman embryonic stem cellssodium alginate microspheres

Identifiers

PMID36231094
PMCPMC9562699
OpenAlexW4303628861

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.