Development of a human salivary gland-on-a-chip composed of both parenchyma and stroma to model dry mouth caused by radiotherapy

Hypofunction of salivary gland, also called dry mouth syndrome, is a common pathological condition in Sjögren's syndrome patients and patients treated with radiotherapy for head and neck cancer. Dry mouth syndrome significantly impairs the quality of life of affected patients. Current treatments can only temporarily relieve the symptoms. Some novel treatments showed promising effects in animal models, but the clinical potentials of these new therapies are difficult to evaluate due to significant differences in salivary gland structures and biology between commonly used animal models and human, and the lack of faithful human tissue culture models. The goal of this proposal is to establish human salivary gland organs-on-a-chip (OoC) models of normal and radiated salivary glands that allow mechanism studies and drug screening for dry mouth syndrome caused by radiotherapy. Currently available salivary gland OoC models are limited, focusing only on epithelial cell components. Recent studies, including those in my lab, have shown that both salivary gland endothelial cells and macrophages are the most radiation-sensitive cells and essential regulators of salivary gland homeostasis and regeneration. Therefore, we will: 1) develop a normal salivary gland OoC model composed of epithelial cells, endothelial cells, and macrophages, and validate its secretory functions; 2) develop the disease salivary gland model based on the normal OOC model that mimick irradiation damage. These models are expected to significantly improve drug development efforts towards restoration of salivary gland functions in head and neck cancer patients treated with radiotherapy. The normal SG OoC will also serve as a platform for studying salivary gland toxicity of drugs for other diseases and dry mouth caused by Sjögren's syndrome in future. Project Number: 1R21DE035318-01 | Fiscal Year: 2025 | NIH Institute/Center: National Institute of Dental and Craniofacial Research (NIDCR) | Principal Investigator: Fei Liu | Institution: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR, COLLEGE STATION, TX | Award Amount: $409,960 | Activity Code: R21 | Study Section: Special Emphasis Panel[ZDE1 JC (09)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11234568