ArticleHepatology (Baltimore, Md.)2022
Aquaporin 9 induction in human iPSC-derived hepatocytes facilitates modeling of ornithine transcarbamylase deficiency.
Article in Hepatology (Baltimore, Md.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- Application of Induced Pluripotent Stem Cells (iPSCs) in Hereditary and Viral Diseases of the Liver: Modeling and Treatment.International journal of molecular sciences · 2025Review
- Novel Treatment Strategy for Patients With Urea Cycle Disorders: Pharmacological Chaperones Enhance Enzyme Stability and Activity in Patient-Derived Liver Disease Models.Journal of inherited metabolic disease · 2025Article
- Review
- Characterization and treatment monitoring of ureagenesis disorders using stable isotopes.npj metabolic health and disease · 2025Article
- Article
- Induced pluripotent stem cell-derived hepatocytes reveal TCA cycle disruption and the potential basis for triheptanoin treatment for malate dehydrogenase 2 deficiency.Molecular genetics and metabolism reports · 2024Article
- Induced pluripotent stem cell technology as diagnostic tool in patients with suspected ornithine transcarbamylase deficiency lacking genetic confirmation.Molecular genetics and metabolism reports · 2023Article
- Pluripotent Stem Cell-Derived Hepatocyte-like Cells: Induction Methods and Applications.International journal of molecular sciences · 2023Review
- Modelling urea cycle disorders using iPSCs.NPJ Regenerative medicine · 2022Review
- Stem Cell Therapies for Chronic Liver Diseases: Progress and Challenges.Stem cells translational medicine · 2022Review
- Aquaporin 9 induction in human iPSC-derived hepatocytes facilitates modeling of ornithine transcarbamylase deficiency.Hepatology (Baltimore, Md.) · 2022Article
- The Multifaceted Role of Aquaporin-9 in Health and Its Potential as a Clinical Biomarker.Biomolecules · 2022Review
- Advancements in Disease Modeling and Drug Discovery Using iPSC-Derived Hepatocyte-like Cells.Genes · 2022Review
- [Clinical research in cell therapy of liver diseases: progress and challenges].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2022Review
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Authors and funding
10 authors at 7 institutions in 2 countries.
Funding
Abstract
BACKGROUND AND
aimsPatient-derived human-induced pluripotent stem cells (hiPSCs) differentiated into hepatocytes (hiPSC-Heps) have facilitated the study of rare genetic liver diseases. Here, we aimed to establish an in vitro liver disease model of the urea cycle disorder ornithine transcarbamylase deficiency (OTCD) using patient-derived hiPSC-Heps. APPROACH AND
resultsBefore modeling OTCD, we addressed the question of why hiPSC-Heps generally secrete less urea than adult primary human hepatocytes (PHHs). Because hiPSC-Heps are not completely differentiated and maintain some characteristics of fetal PHHs, we compared gene-expression levels in human fetal and adult liver tissue to identify genes responsible for reduced urea secretion in hiPSC-Heps. We found lack of aquaporin 9 (AQP9) expression in fetal liver tissue as well as in hiPSC-Heps, and showed that forced expression of AQP9 in hiPSC-Heps restores urea secretion and normalizes the response to ammonia challenge by increasing ureagenesis. Furthermore, we proved functional ureagenesis by challenging AQP9-expressing hiPSC-Heps with ammonium chloride labeled with the stable isotope [
conclusionOur results identify a critical role for AQP9 in functional urea metabolism and establish the feasibility of in vitro modeling of OTCD with hiPSC-Heps. By facilitating studies of OTCD genotype/phenotype correlation and drug screens, our model has potential for improving the therapy of OTCD.
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