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Updated: Aug 7, 2025
Production, Characterization and Potential Uses of a 3D Tissue-engineered Human Esophageal Mucosal Model
Published on: May 18, 2015
Transcriptome Sequencing Reveals the Mechanism behind Chemically Induced Oral Mucositis in a 3D Cell Culture Model
Maria Lambros1, Jonathan Moreno1, Qinqin Fei1
1Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA.
Abstract:
Oral mucositis is a common side effect of cancer treatment, and in particular of treatment with the mTORC1 inhibitor everolimus. Current treatment methods are not efficient enough and a better understanding of the causes and mechanisms behind oral mucositis is necessary to find potential therapeutic targets. Here, we treated an organotypic 3D oral mucosal tissue model consisting of human keratinocytes grown on top of human fibroblasts with a high or low dose of everolimus for 40 or 60 h and investigated (1) the effect of everolimus on microscopic sections of the 3D cell culture for evidence of morphologic changes and (2) changes in the transcriptome by high throughput RNA-Seq analysis. We show that the most affected pathways are cornification, cytokine expression, glycolysis, and cell proliferation and we provide further details. This study provides a good resource towards a better understanding of the development of oral mucositis. It gives a detailed overview of the different molecular pathways that are involved in mucositis. This in turn provides information about potential therapeutic targets, which is an important step towards preventing or managing this common side effect of cancer treatment.
Insights
This study investigated oral mucositis caused by everolimus cancer treatment. Researchers found that everolimus significantly impacts cornification, cytokine expression, glycolysis, and cell proliferation pathways.
Area of Science:
- Oncology
- Cell Biology
- Tissue Engineering
Background:
- Oral mucositis is a frequent adverse effect of cancer therapies, particularly with mTORC1 inhibitors like everolimus.
- Current treatments for oral mucositis are often insufficient, necessitating a deeper understanding of its underlying mechanisms.
Purpose of the Study:
- To investigate the molecular mechanisms of oral mucositis induced by everolimus.
- To identify potential therapeutic targets for mitigating this side effect.
Main Methods:
- Utilized an organotypic 3D oral mucosal tissue model composed of human keratinocytes and fibroblasts.
- Treated the model with varying doses and durations of everolimus.
- Analyzed morphologic changes via microscopy and transcriptomic alterations using high-throughput RNA-Seq.
Main Results:
- Everolimus treatment led to significant alterations in key biological pathways.
- Specifically affected pathways included cornification, cytokine expression, glycolysis, and cell proliferation.
- Morphological changes were observed in the 3D oral mucosal tissue model.
Conclusions:
- The study elucidates the molecular pathways involved in everolimus-induced oral mucositis.
- Identified specific pathways provide insights into potential therapeutic targets for prevention or management.
- This research serves as a valuable resource for understanding and addressing oral mucositis.
