ArticleHepatology (Baltimore, Md.)2015
Induced pluripotent stem cells model personalized variations in liver disease resulting from α1-antitrypsin deficiency.
Article in Hepatology (Baltimore, Md.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07639996 (Natural Course and Molecular Basis of Alpha 1- Antitrypsin Deficiency-associated Liver Disease.), which is not on this map. Cited by 50 papers.
What it found
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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.
Natural Course and Molecular Basis of Alpha 1- Antitrypsin Deficiency-associated Liver Disease.
Who cites it
50 citing papers in PubMed, 84 citations in OpenAlex.
- AT2-intrinsic Z-AAT expression drives conserved inflammatory and proteotoxic stress responses and predisposes to emphysema.bioRxiv : the preprint server for biology · 2026Article
- Z variant heterozygosity in alpha-1 antitrypsin deficiency: disease risk and treatment implications.Orphanet journal of rare diseases · 2026Article
- Generation and applications of an expandable and mature hiPSC-derived liver organoid.Acta pharmaceutica Sinica. B · 2025Article
- Application of Induced Pluripotent Stem Cells (iPSCs) in Hereditary and Viral Diseases of the Liver: Modeling and Treatment.International journal of molecular sciences · 2025Review
- Rationale and Design of the Alpha-1 Biomarkers Consortium Study.Chronic obstructive pulmonary diseases (Miami, Fla.) · 2025Article
- Review
- Exploring the promising potential of induced pluripotent stem cells in cancer research and therapy.Molecular cancer · 2023Review
- Pluripotent Stem Cell-Derived Hepatocyte-like Cells: Induction Methods and Applications.International journal of molecular sciences · 2023Review
- Development of a method of passaging and freezing human iPS cell-derived hepatocytes to improve their functions.PloS one · 2023Article
- Human iPSC-hepatocyte modeling of alpha-1 antitrypsin heterozygosity reveals metabolic dysregulation and cellular heterogeneity.Cell reports · 2022Article
- From a Single Cell to a Whole Human Liver: Disease Modeling and Transplantation.Seminars in liver disease · 2022Article
- Pluripotent Stem Cell-derived Strategies to Treat Acute Liver Failure: Current Status and Future Directions.Journal of clinical and translational hepatology · 2022Review
- Regulation of PGC1α Downstream of the Insulin Signaling Pathway Plays a Role in the Hepatic Proteotoxicity of Mutant α1-Antitrypsin Deficiency Variant Z.Gastroenterology · 2022Article
- From Cells to Organs: The Present and Future of Regenerative Medicine.Advances in experimental medicine and biology · 2022Review
- Review
- Synthetic human livers for modeling metabolic diseases.Current opinion in gastroenterology · 2021Review
- Human biomimetic liver microphysiology systems in drug development and precision medicine.Nature reviews. Gastroenterology & hepatology · 2021Review
- Current status of hepatocyte-like cell therapy from stem cells.Surgery today · 2021Review
- The Application of Induced Pluripotent Stem Cells Against Liver Diseases: An Update and a Review.Frontiers in medicine · 2021Review
- Liver Fibrosis-From Mechanisms of Injury to Modulation of Disease.Frontiers in medicine · 2021Review
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
unlabelledIn the classical form of α1-antitrypsin deficiency (ATD), aberrant intracellular accumulation of misfolded mutant α1-antitrypsin Z (ATZ) in hepatocytes causes hepatic damage by a gain-of-function, "proteotoxic" mechanism. Whereas some ATD patients develop severe liver disease (SLD) that necessitates liver transplantation, others with the same genetic defect completely escape this clinical phenotype. We investigated whether induced pluripotent stem cells (iPSCs) from ATD individuals with or without SLD could model these personalized variations in hepatic disease phenotypes. Patient-specific iPSCs were generated from ATD patients and a control and differentiated into hepatocyte-like cells (iHeps) having many characteristics of hepatocytes. Pulse-chase and endoglycosidase H analysis demonstrate that the iHeps recapitulate the abnormal accumulation and processing of the ATZ molecule, compared to the wild-type AT molecule. Measurements of the fate of intracellular ATZ show a marked delay in the rate of ATZ degradation in iHeps from SLD patients, compared to those from no liver disease patients. Transmission electron microscopy showed dilated rough endoplasmic reticulum in iHeps from all individuals with ATD, not in controls, but globular inclusions that are partially covered with ribosomes were observed only in iHeps from individuals with SLD.
conclusioniHeps model the individual disease phenotypes of ATD patients with more rapid degradation of misfolded ATZ and lack of globular inclusions in cells from patients who have escaped liver disease. The results support the concept that "proteostasis" mechanisms, such as intracellular degradation pathways, play a role in observed variations in clinical phenotype and show that iPSCs can potentially be used to facilitate predictions of disease susceptibility for more precise and timely application of therapeutic strategies.
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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.