ArticlePloS one2020
Patient-derived oral mucosa organoids as an in vitro model for methotrexate induced toxicity in pediatric acute lymphoblastic leukemia.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Oral Mucositis in Oncopediatric Patients: MTX and MMP-1, MMP-8, MMP-13 Gene Polymorphisms.Oral diseases · 2026Article
- Identification of stem cell marker-positive subpopulations in the vocal fold of the larynx through transcriptomic analyses.Nature communications · 2026Article
- An organoid-guided roadmap for precision delivery of epigallocatechin gallate in oral submucous fibrosis.Frontiers in bioengineering and biotechnology · 2026Review
- Oral tissue spheroid, organoid, and organ-on chip microphysiological modeling strategies towards enhanced emulation of health and disease.Bioengineering & translational medicine · 2025Review
- Advanced Animal Replacement Testing Strategies Using Stem Cell and Organoids.International journal of stem cells · 2025Review
- Biomedical applications of organoids derived from the digestive system.Frontiers in cell and developmental biology · 2025Review
- Organoids in the oral and maxillofacial region: present and future.International journal of oral science · 2024Review
- Complications and comorbidities associated with antineoplastic chemotherapy: Rethinking drug design and delivery for anticancer therapy.Acta pharmaceutica Sinica. B · 2024Review
- The role of l-leucovorin uptake and metabolism in the modulation of 5-fluorouracil efficacy and antifolate toxicity.Frontiers in pharmacology · 2024Article
- A novel antifolate suppresses growth of FPGS-deficient cells and overcomes methotrexate resistance.Life science alliance · 2023Article
- Methotrexate Provokes Disparate Folate Metabolism Gene Expression and Alternative Splicing in Ex Vivo Monocytes and GM-CSF- and M-CSF-Polarized Macrophages.International journal of molecular sciences · 2023Article
- Review
- The applications and techniques of organoids in head and neck cancer therapy.Frontiers in oncology · 2023Review
- Profiling of mature-stage human breast milk cells identifies six unique lactocyte subpopulations.Science advances · 2022Article
- Development of a self-limiting model of methotrexate-induced mucositis reinforces butyrate as a potential therapy.Scientific reports · 2021Article
- Organoids in image-based phenotypic chemical screens.Experimental & molecular medicine · 2021Review
- Review
- Article
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have recently established a protocol to grow wildtype human oral mucosa organoids. These three-dimensional structures can be maintained in culture long-term, do not require immortalization, and recapitulate the multilayered composition of the epithelial lining of the oral mucosa. Here, we validate the use of this model to study the effect of Leucovorin (LV) on Methotrexate (MTX)-induced toxicity. MTX is a chemotherapeutic agent used in the treatment of pediatric acute lymphoblastic leukemia. Although effective, the use of MTX often results in severe side-effects, including oral mucositis, which is characterized by epithelial cell death. Here, we show that organoids are sensitive to MTX, and that the addition of LV reduces MTX toxicity, in both a concentration- and timing-dependent manner. Additionally, we show that a 24 hour 'pretreatment' with LV reduces MTX-induced cell death, suggesting that such a pretreatment could decrease mucositis in patients. Taken together, we provide the first in vitro model to study the effect of MTX on wildtype oral mucosa cells. Our findings underscore the relevance of the clinically applied LV regimen and highlight the potential of this model to further optimize modifications in dosing and timing of Leucovorin on oral mucosa cells.
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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.