ArticleStem cell research & therapy2018
Recapitulation of methotrexate hepatotoxicity with induced pluripotent stem cell-derived hepatocytes from patients with rheumatoid arthritis.
Article in Stem cell research & therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 32 citations in OpenAlex.
- Transcriptomic Profile of Directed Differentiation of iPSCs into Hepatocyte-like Cells.International journal of molecular sciences · 2026Article
- High paracrine activity of hADSCs cartilage microtissues inhibits extracellular matrix degradation and promotes cartilage regeneration.Materials today. Bio · 2025Article
- 3D bioprinting for the construction of drug testing models-development strategies and regulatory concerns.Frontiers in bioengineering and biotechnology · 2025Review
- The dual anti-inflammatory and anticoagulant effects of Jianpi Huashi Tongluo prescription on Rheumatoid Arthritis through inhibiting the activation of the PI3K/AKT signaling pathway.Frontiers in pharmacology · 2025Article
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- 3D in vitro synovial hyperplasia model on polycaprolactone-micropatterned nanofibrous microwells for screening disease-modifying anti-rheumatic drugs.Materials today. Bio · 2024Article
- Research progress of autoimmune diseases based on induced pluripotent stem cells.Frontiers in immunology · 2024Review
- Investigation of immune-related diseases using patient-derived induced pluripotent stem cells.Inflammation and regeneration · 2023Review
- Shining the light on clinical application of mesenchymal stem cell therapy in autoimmune diseases.Stem cell research & therapy · 2022Review
- Integrated Microbiome and Metabolome Analysis Reveals Correlations Between Gut Microbiota Components and Metabolic Profiles in Mice with Methotrexate-Induced Hepatoxicity.Drug design, development and therapy · 2022Article
- Review
- Identification of miR-199a-5p, miR-214-3p and miR-99b-5p as Fibrosis-Specific Extracellular Biomarkers and Promoters of HSC Activation.International journal of molecular sciences · 2021Article
- Advancements in stem cell-derived hepatocyte-like cell models for hepatotoxicity testing.Stem cell research & therapy · 2021Review
- Dysregulation of Cells Cycle and Apoptosis in Human Induced Pluripotent Stem Cells Chondrocytes Through p53 Pathway by HT-2 Toxin: AnFrontiers in genetics · 2021Article
- Analysis of association of ADORAThe pharmacogenomics journal · 2020Article
- Combination therapy of ginsenoside compound K and methotrexate was efficient in elimination of anaemia and reduction of disease activity in adjuvant-induced arthritis rats.Pharmaceutical biology · 2020Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundMethotrexate (MTX) is widely used for the treatment of rheumatoid arthritis (RA). The drug is cost-effective, but sometimes causes hepatotoxicity, requiring a physician's attention. In this study, we simulated hepatotoxicity by treating hepatocytes derived from RA patient-derived induced pluripotent stem cells (RA-iPSCs) with MTX.
methodsRA-iPSCs and healthy control iPSCs (HC-iPSCs) were established successfully. RA-iPSCs were differentiated into hepatocytes in two-dimensional (2D) monolayers and three-dimensional (3D) hepatocyte spheroid cultures; this process required growth factors such as BMP4, bFGF, HGF, and OSM. Immunofluorescence staining and flow cytometry were performed to confirm that the mature hepatocytes expressed cytokeratin 18, anti-alpha-1 antitrypsin, and albumin. MTX toxicity was evaluated via monitoring of cell viability, alanine aminotransferase, and mitochondrial status after MTX treatment in 2D and 3D cultures.
resultsRA-iPSCs generated from three RA patients suffering from MTX-induced hepatotoxicity differentiated into the endoderm lineage, hepatoblasts, and hepatocytes. In 2D culture, RA-iPSC-derived hepatocytes were more sensitive to MTX than healthy controls. A 3D culture system using hepatocyte spheroids also successfully recapitulated MTX-induced hepatotoxicity. The 3D culture system had several advantages, including longer culture periods under more complex conditions.
conclusionsA patient-derived iPSC platform could recapitulate MTX toxicity. Simulation of drug toxicity in vitro may help clinicians choose safer drugs or less toxic doses.
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