ArticleScientific reports2016
Scalable Differentiation of Human iPSCs in a Multicellular Spheroid-based 3D Culture into Hepatocyte-like Cells through Direct Wnt/β-catenin Pathway Inhibition.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 83 citations in OpenAlex.
- A comprehensive transcriptomic comparison of hepatocyte model systems improves selection of models for experimental use.Communications biology · 2022Pooled it
- Scalable synthetic peptide hydrogel enables self-organized luminal cavity architecture within hiPSC 3D colonies supporting functional hepatocyte differentiation.Bioactive materials · 2026Article
- Generation and applications of an expandable and mature hiPSC-derived liver organoid.Acta pharmaceutica Sinica. B · 2025Article
- Human-Induced Pluripotent Stem Cell-Derived Definitive Endoderm Bulk Up and Hepatic Differentiation.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Liver organoids: updates on generation strategies and biomedical applications.Stem cell research & therapy · 2024Review
- Review
- Cryopreserved cGMP-compliant human pluripotent stem cell-derived hepatic progenitors rescue mice from acute liver failure through rapid paracrine effects on liver cells.Stem cell research & therapy · 2024Article
- Multicellular Liver Organoids: Generation and Importance of Diverse Specialized Cellular Components.Cells · 2023Review
- Dialysis based-culture medium conditioning improved the generation of human induced pluripotent stem cell derived-liver organoid in a high cell density.Scientific reports · 2022Article
- Article
- Review
- Targeting Wnt/β-Catenin Pathways in Primary Liver Tumours: From Microenvironment Signaling to Therapeutic Agents.Cancers · 2022Review
- Generation of Hepatocyte Organoids from Human iPS Cells.Methods in molecular biology (Clifton, N.J.) · 2022Article
- CRISPR-Mediated Genomic Addition to CPS1 Deficient iPSCs is Insufficient to Restore Nitrogen Homeostasis.The Yale journal of biology and medicine · 2021Article
- Article
- Quality Verification with a Cluster-Controlled Manufacturing System to Generate Monocyte-Derived Dendritic Cells.Vaccines · 2021Article
- Microengineered systems with iPSC-derived cardiac and hepatic cells to evaluate drug adverse effects.Experimental biology and medicine (Maywood, N.J.) · 2021Review
- Human liver model systems in a dish.Development, growth & differentiation · 2021Review
- Engineered Liver Tissue Culture in anTissue engineering. Part A · 2020Article
- Engineering liver microtissues for disease modeling and regenerative medicine.Advanced functional materials · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Treatment of acute liver failure by cell transplantation is hindered by a shortage of human hepatocytes. Current protocols for hepatic differentiation of human induced pluripotent stem cells (hiPSCs) result in low yields, cellular heterogeneity, and limited scalability. In the present study, we have developed a novel multicellular spheroid-based hepatic differentiation protocol starting from embryoid bodies of hiPSCs (hiPSC-EBs) for robust mass production of human hepatocyte-like cells (HLCs) using two novel inhibitors of the Wnt pathway. The resultant hiPSC-EB-HLCs expressed liver-specific genes, secreted hepatic proteins such as Albumin, Alpha Fetoprotein, and Fibrinogen, metabolized ammonia, and displayed cytochrome P450 activities and functional activities typical of mature primary hepatocytes, such as LDL storage and uptake, ICG uptake and release, and glycogen storage. Cell transplantation of hiPSC-EB-HLC in a rat model of acute liver failure significantly prolonged the mean survival time and resolved the liver injury when compared to the no-transplantation control animals. The transplanted hiPSC-EB-HLCs secreted human albumin into the host plasma throughout the examination period (2 weeks). Transplantation successfully bridged the animals through the critical period for survival after acute liver failure, providing promising clues of integration and full in vivo functionality of these cells after treatment with WIF-1 and DKK-1.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.