Evidence map›Paper›PMID 42069598›Full record

ArticleJournal of nanobiotechnology2026

High-throughput human microfluidic organoid-on-a-chip platform for modeling liver diseases and screening nanotherapeutics.

Defu Kong, Shihang Yu, Janette Heegsma, Tjasso Blokzijl, Tian Qin, Yixiao Pan, Hans Blokzijl, Vincent E de Meijer, Yourong Duan, Klaas Nico Faber and 2 more

Abstract read
In one paragraph

Article in Journal of nanobiotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. 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

12 authors.

Defu Kong *Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. kongdefu@sjtu.edu.cn.
Shihang Yu *Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Janette HeegsmaDepartment of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Tjasso BlokzijlDepartment of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Tian QinDepartment of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Yixiao PanDepartment of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Hans BlokzijlDepartment of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Vincent E de MeijerDepartment of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Yourong DuanState Key Laboratory of Systems Medicine for Cancer, Renji Hospital, School of Medicine, Shanghai Cancer Institute, Shanghai Jiao Tong University, Shanghai, 200032, China.
Klaas Nico FaberDepartment of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. k.n.faber@umcg.nl.
Qiang XiaDepartment of Liver Surgery and Liver Transplantation, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. xiaqiang@shsmu.edu.cn.
Kang HeDepartment of Liver Surgery and Liver Transplantation, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. hekang@renji.com.

Funding

Shanghai Natural Science Foundation 23ZR1438600Shanghai Research Center for Organ Transplantation, Category A Key Research Center of Shanghai Municipality 2022ZZ01016Special Program of the National Natural Science Foundation of China 82241221
6 · The paper itself

Abstract

backgroundHuman liver tissue-derived organoids recapitulate key hepatic phenotypes but are commonly maintained under static conditions, whereas microfluidic organ-on-chip systems provide controllable perfusion and mass transport. Scalable integration of human liver tissue-derived organoids into a perfused, human-relevant Liver-on-Chip remains limited.

resultsWe combined healthy human liver tissue-derived organoids with a high-throughput three-lane OrganoPlate microfluidic format to establish a perfused organoid Liver-on-Chip (HepLoC) featuring 3D luminal tubules under continuous flow. After hepatocyte-directed differentiation under perfusion, bioengineered HepLoC formed mature hepatocyte-like architectures with increased mature hepatocyte marker proteins, enrichment of hepatic transcriptomic signatures, and functional bile canaliculi. As a proof-of-concept for drug-induced liver injury, troglitazone induced dose-dependent hepatocyte injury accompanied by tight-junction disruption, MRP2 mislocalization, and impaired bile acid export, recapitulating key features of cholestatic liver injury. To model metabolic liver disease, free fatty acids triggered lipid droplet accumulation, increased triglycerides and reactive oxygen species, and upregulated lipogenic and inflammatory genes while largely preserving viability, consistent with early-stage metabolic dysfunction-associated fatty liver disease. The high-throughput HepLoC format further enabled parallel testing of reference hepatotoxic drugs and curcumin liposomes by reduced lipid accumulation in fatty-acid-treated HepLoC with minimal hepatotoxicity.

conclusionsOur perfused, organoid-based microfluidic Liver-on-Chip recapitulates essential human liver structure and function and enables integrated, parallel evaluation of hepatotoxicity and optimization of nanotherapeutic strategies, which deciphers the mechanisms of liver diseases, bridging the gap between preclinical research and clinical translation.

Indexed as

High-Throughput Screening AssaysLiver DiseasesMicrophysiological SystemsOrganoidsCell DifferentiationChemical and Drug Induced Liver InjuryDrug Evaluation, PreclinicalHepatocytesHumansLiverMicrofluidicsMultidrug Resistance-Associated Protein 2NanomedicineTroglitazoneABCC2 protein, humanMultidrug Resistance-Associated Protein 2TroglitazoneBile canaliculiCholestasisDrug-induced liver injuryHigh-throughput screeningLipid nanoparticleLiver-on-ChipMAFLD, nanomedicineMicrofluidicsOrganoid-on-chip

Identifiers

PMID42069598
PMCPMC13285093

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.