ArticleHepatology international2020
Liver organoids reproduce alpha-1 antitrypsin deficiency-related liver disease.
Article in Hepatology international, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 70 citations in OpenAlex.
- Hepatic control of immunometabolism: implications for the pathogenesis, diagnosis and treatment of rheumatic diseases.Nature reviews. Rheumatology · 2026Review
- Organoids in drug development: from predictive models to regulatory integration.Drug discovery today · 2026Review
- Human organoids as 3D in vitro platforms for drug discovery: opportunities and challenges.Nature reviews. Drug discovery · 2026Review
- Stem cells in organogenesis and regeneration.Stem cell research & therapy · 2026Review
- The Role of Alpha-1 Antitrypsin in the Pathophysiology and Treatment of Inflammatory Lung Diseases.Journal of inflammation research · 2026Review
- Organoids in Cancer Research and Regenerative Medicine: Current Status, Challenges, and Future Prospects.MedComm · 2026Review
- Next-Generation Regenerative Therapies for Alpha-1 Antitrypsin Deficiency: Molecular Pathogenesis to Clinical Translation.International journal of molecular sciences · 2025Review
- [Liver organoid technology and its related progress in liver disease research].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025Review
- High-Throughput Formation of Pre-Vascularized hiPSC-Derived Hepatobiliary Organoids on a Chip via Nonparenchymal Cell Grafting.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Advances in liver organoids: replicating hepatic complexity for toxicity assessment and disease modeling.Stem cell research & therapy · 2025Review
- Hepatobiliary organoid research: the progress and applications.Frontiers in pharmacology · 2025Review
- Genetic and clinical factors influencing CF-associated liver disease: the impact ofMedicine and pharmacy reports · 2024Article
- Research progress and application of liver organoids for disease modeling and regenerative therapy.Journal of molecular medicine (Berlin, Germany) · 2024Review
- Organoid-based personalized medicine: from tumor outcome prediction to autologous transplantation.Stem cells (Dayton, Ohio) · 2024Review
- Article
- Prediction for oxaliplatin-induced liver injury using patient-derived liver organoids.Cancer medicine · 2024Article
- Advances, challenges and future applications of liver organoids in experimental regenerative medicine.Frontiers in medicine · 2024Review
- Trends and challenges in organoid modeling and expansion with pluripotent stem cells and somatic tissue.PeerJ · 2024Review
- Liver organoid culture methods.Cell & bioscience · 2023Review
- Organoid Establishment of Long-Term Culture Using Primary Mouse Hepatocytes and Evaluation of Liver Function.Preventive nutrition and food science · 2023Article
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Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
Abstract
BACKGROUND AND
aimsAlpha-1 antitrypsin (AAT) is a product of SERPINA1 gene mainly expressed by hepatocytes. Clinically relevant mutations in the SERPINA1 gene, such as Z (Glu342Lys), results in an expression of misfolded AAT protein having high propensity to polymerize, accumulate in hepatocytes and thus to enhance a risk for hepatocyte damage and subsequent liver disease. So far, the relationship between the Z-AAT accumulation and liver cell damage remains not completely understood. We present three-dimensional organoid culture systems, as a novel tool for modeling Z-AAT-related liver diseases.
methodsWe have established liver organoids from liver biopsies of patients with homozygous (ZZ) and heterozygous (MZ) deficiency and normal (MM) genotypes of AAT. The features of these organoid models were characterized by analyzing AAT protein secretion and intracellular aggregation in MZ and ZZ genotypes as well as SERPINA1 expression in differentiated cultures.
resultsTranscriptional analysis of differentiated organoid cultures by RNA-Seq showed hepatocyte-specific gene expression profile. Genes, such as ALB, APOB, CYP3A4 and SERPINA1, were validated and confirmed through quantitative-PCR analysis. The organoids from MZ and ZZ cases showed intracellular aggregation and lower secretion of AAT protein, and lower expression of ALB and APOB, as typically seen in hepatocytes from Z-AAT deficiency patients. Furthermore, organoids responded to external stimulus. Treatment with oncostatin M, a well-known inducer of SERPINA1, increased expression of the full-length transcripts (AAT-1C) as well as the short transcript of AAT (AAT-ST1C4).
conclusionsLiver organoid model recapitulates the key features of Z-AAT deficiency and provides a useful tool for disease modeling.
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