Evidence map›Paper›PMID 36404924›Full record

ArticleiScience2022

Biofabrication of synthetic human liver tissue with advanced programmable functions.

Rodrigo M Florentino, Kazutoyo Morita, Nils Haep, Takashi Motomura, Ricardo Diaz-Aragon, Lanuza A P Faccioli, Alexandra Collin de l'Hortet, Zeliha Cetin, Carla Frau, Lawrence Vernetti and 8 more

Open access · goldAbstract read
In one paragraph

Article in iScience, 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
0.6field-weighted citation impact, top 35% 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.

  1. Article
  2. Review
  3. Article
  4. Article
  5. 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

18 authors at 2 institutions in 2 countries.

Rodrigo M FlorentinoDepartment of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.
Kazutoyo MoritaDepartment of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.
Nils HaepDepartment of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.
Takashi MotomuraDepartment of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.
Ricardo Diaz-AragonDepartment of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.
Lanuza A P FaccioliDepartment of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.
Alexandra Collin de l'HortetDepartment of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.
Zeliha CetinDepartment of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.
Carla FrauDepartment of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.
Lawrence VernettiPittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA, USA.
Anna-Klara AmlerCellbricks GmbH, Gustav-Meyer-Allee 25, 13355 Berlin, Germany.
Alexander ThomasCellbricks GmbH, Gustav-Meyer-Allee 25, 13355 Berlin, Germany.
Tobias LamCellbricks GmbH, Gustav-Meyer-Allee 25, 13355 Berlin, Germany.
Lutz KlokeCellbricks GmbH, Gustav-Meyer-Allee 25, 13355 Berlin, Germany.
Kazuki TakeishiDepartment of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.
D Lansing TaylorPittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA, USA.
Ira J FoxDepartment of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA, USA.
Alejandro Soto-GutierrezDepartment of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.
University of Pittsburgh · USKyushu University · JP

Funding

Treating AT Deficiency with Drugs that Modulate the Proteostasis NetworkP01DK096990 · NIDDK · WASHINGTON UNIVERSITY · PI FOX, IRA J. · 2012 to 2023
$18.3M
Pittsburgh Liver Research CenterP30DK120531 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DAVID A GELLER · 2019 to 2026
$10.9M
Harnessing human brain and liver microphysiological systems for testing therapeutics for metastatic melanomaU01TR002383 · NCATS · VANDERBILT UNIVERSITY · PI MURPHY, WILLIAM L., TAYLOR, D. LANSING · 2018 to 2022
$7.6M
Human Microphysiology Systems Disease Model of Type 2 Diabetes Starting with Liver and pancreatic IsletsUH3DK119973 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI TAYLOR, D. LANSING · 2020 to 2022
$6.7M
Mini-Livers Derived from Human IPS Cells for Modeling Steatosis and TherapyR01DK099257 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI NAGRATH, DEEPAK, SOTO-GUTIERREZ, ALEJANDRO · 2014 to 2024
$3.4M
Applying a Human Liver Microphysiology System to Develop Therapeutic Strategies for Non-Alcoholic Fatty Liver Disease (NAFLD)R01DK117881 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI TAYLOR, D. LANSING · 2018 to 2021
$2.7M
Human Microphysiology Systems Disease Model of Type 2 Diabetes Starting with Liver and pancreatic IsletsUG3DK119973 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI TAYLOR, D. LANSING · 2018 to 2019
$2.3M
A vascularized patient-derived iPSC liver acinus microphysiology system as an innovative precision medicine platform for optimizing clinical trial design for nonalcoholic fatty liver diseaseUH3TR003289 · NCATS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BEHARI, JAIDEEP, SOTO-GUTIERREZ, ALEJANDRO · 2022 to 2024
$2.3M
A vascularized patient-derived iPSC liver acinus microphysiology system as an innovative precision medicine platform for optimizing clinical trial design for nonalcoholic fatty liver diseaseUG3TR003289 · NCATS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BEHARI, JAIDEEP, SOTO-GUTIERREZ, ALEJANDRO · 2020 to 2021
$1.5M
NCATS NIH HHS U01 TR002383NCATS NIH HHS UG3 TR003289NCATS NIH HHS UH3 TR003289NIDDK NIH HHS P01 DK096990NIDDK NIH HHS P30 DK120531NIDDK NIH HHS R01 DK099257NIDDK NIH HHS R01 DK117881NIDDK NIH HHS UG3 DK119973NIDDK NIH HHS UH3 DK119973
6 · The paper itself

Abstract

Advances in cellular engineering, as well as gene, and cell therapy, may be used to produce human tissues with programmable genetically enhanced functions designed to model and/or treat specific diseases. Fabrication of synthetic human liver tissue with these programmable functions has not been described. By generating human iPSCs with target gene expression controlled by a guide RNA-directed CRISPR-Cas9 synergistic-activation-mediator, we produced synthetic human liver tissues with programmable functions. Such iPSCs were guide-RNA-treated to enhance expression of the clinically relevant CYP3A4 and UGT1A1 genes, and after hepatocyte-directed differentiation, cells demonstrated enhanced functions compared to those found in primary human hepatocytes. We then generated human liver tissue with these synthetic human iPSC-derived hepatocytes (iHeps) and other non-parenchymal cells demonstrating advanced programmable functions. Fabrication of synthetic human liver tissue with modifiable functional genetic programs may be a useful tool for drug discovery, investigating biology, and potentially creating bioengineered organs with specialized functions.

Indexed as

BioengineeringBiological sciencesTissue engineering

Identifiers

PMID36404924
PMCPMC9672940
OpenAlexW4309035350

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.