Evidence map›Paper›PMID 31222080›Full record

ArticleScientific reports2019

Generation of fully functional hepatocyte-like organoids from human induced pluripotent stem cells mixed with Endothelial Cells.

Giuseppe Pettinato, Sylvain Lehoux, Rajesh Ramanathan, Mohamed M Salem, Li-Xia He, Oluwatoyosi Muse, Robert Flaumenhaft, Melissa T Thompson, Emily A Rouse, Richard D Cummings and 2 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
88citing papers in PubMed, 1 pooled it
8.1field-weighted citation impact, top 2% 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

88 citing papers in PubMed, 1 synthesis or guideline pooled it, 159 citations in OpenAlex.

  1. Pooled it
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  18. Frontiers in cell and developmental biology · 2024
    Article
  19. iPSC-derived cells for whole liver bioengineering.Frontiers in bioengineering and biotechnology · 2024
    Review
  20. Article

28 more citing papers are in PubMed but not listed here.

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

12 authors at 4 institutions in 1 country.

Giuseppe PettinatoDepartment of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. gpettina@bidmc.harvard.edu.
Sylvain LehouxDepartment of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Rajesh RamanathanDepartment of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Mohamed M SalemDepartment of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Li-Xia HeDepartment of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Oluwatoyosi MuseDepartment of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Robert FlaumenhaftDepartment of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Melissa T ThompsonDepartment of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Emily A RouseGlycomics Core, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Richard D CummingsDepartment of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Xuejun WenDepartment of Chemical and Life Science Engineering, Virginia Commonwealth University, Richmond, VA, USA.
Robert A FisherDepartment of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. rafisher@bidmc.harvard.edu.
Beth Israel Deaconess Medical Center · USHarvard University · USUniversity of Pittsburgh Medical Center · USVirginia Commonwealth University · US

Funding

PROGRAM IN BLOOD COAGULATION AND VASCULAR BIOLOGYT32HL007917 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI Robert C Flaumenhaft · 1999 to 2026
$11.1M
Overall Priority Score P41GM103694 · NIGMS · EMORY UNIVERSITY · PI CUMMINGS, RICHARD D · 2013 to 2018
$6.9M
Thiol Isomerases in Hemostasis and ThrombosisR35HL135775 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI FLAUMENHAFT, ROBERT C · 2017 to 2023
$5.5M
NHLBI NIH HHS R35 HL135775NHLBI NIH HHS T32 HL007917NIGMS NIH HHS P41 GM103694
6 · The paper itself

Abstract

Despite advances in stem cell research, cell transplantation therapy for liver failure is impeded by a shortage of human primary hepatocytes (HPH), along with current differentiation protocol limitations. Several studies have examined the concept of co-culture of human induced pluripotent cells (hiPSCs) with various types of supporting non-parenchymal cells to attain a higher differentiation yield and to improve hepatocyte-like cell functions both in vitro and in vivo. Co-culturing hiPSCs with human endothelial cells (hECs) is a relatively new technique that requires more detailed studies. Using our 3D human embryoid bodies (hEBs) formation technology, we interlaced Human Adipose Microvascular Endothelial Cells (HAMEC) with hiPSCs, leading to a higher differentiation yield and notable improvements across a wide range of hepatic functions. We conducted a comprehensive gene and protein secretion analysis of our HLCs coagulation factors profile, showing promising results in comparison with HPH. Furthermore, a stage-specific glycomic analysis revealed that the differentiated hepatocyte-like clusters (HLCs) resemble the glycan features of a mature tissue rather than cells in culture. We tested our HLCs in animal models, where the presence of HAMEC in the clusters showed a consistently better performance compared to the hiPSCs only group in regard to persistent albumin secretion post-transplantation.

Indexed as

Cell DifferentiationCell TransplantationCoculture TechniquesEndothelial CellsHepatocytesHumansInduced Pluripotent Stem CellsLiver FailureModels, AnimalOrganoids

Identifiers

PMID31222080
PMCPMC6586904
OpenAlexW2949380546

What Socratic 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 Socratic graph.