Pillai Sangeeth, Munguia-Lopez Jose G, Liu Younan, Gigliotti Jordan, Zeitouni Anthony, Kinsella Joseph M, Tran Simon D
Faculty of Dental Medicine and Oral Health Sciences, McGill University, Montreal, QC, Canada.
Department of Bioengineering, McGill University, Montreal, QC, Canada.
J Tissue Eng. 2025 Apr 30;16:20417314251326667. doi: 10.1177/20417314251326667. eCollection 2025 Jan-Dec.
No permanent cure exists for salivary gland (SG) damage and consequent xerostomia (dry mouth) in patients undergoing radiotherapy for head and neck cancers. The lack of commercially available healthy human SG-derived cell lines has hindered in vitro studies of radiation-induced glandular injury. In this study, we successfully immortalized and characterized two novel human major SG-derived cell lines. Leveraging these cell lines and hyaluronic-acid hydrogels, we bioengineered distinct multicellular SG spheroids and microtissues expressing key acinar, ductal, myoepithelial, and mesenchymal cell markers in long-term cultures. Further, using this platform, we developed a proof-of-concept radiation injury model, demonstrating spheroid disruption characterized by actin depolymerization, DNA damage, apoptosis, and loss of SG-specific markers following radiation exposure. Notably, these detrimental effects were partially mitigated with a radioprotective agent. Our findings demonstrate that the bioengineered SG spheroids provide a scalable and versatile platform with significant potential for disease modeling and drug testing, thereby accelerating the development of targeted therapies for radiation-induced xerostomia.
对于接受头颈癌放疗的患者，唾液腺（SG）损伤及随之而来的口干症（口腔干燥）尚无永久性治愈方法。缺乏可商购的健康人源唾液腺衍生细胞系阻碍了对辐射诱导的腺体损伤的体外研究。在本研究中，我们成功地使两种新型人源主要唾液腺衍生细胞系永生化并进行了表征。利用这些细胞系和透明质酸水凝胶，我们在长期培养中生物工程构建了表达关键腺泡、导管、肌上皮和间充质细胞标志物的不同多细胞唾液腺球体和微组织。此外，利用该平台，我们开发了一个概念验证辐射损伤模型，证明辐射暴露后球体破坏的特征为肌动蛋白解聚、DNA损伤、细胞凋亡和唾液腺特异性标志物丧失。值得注意的是，这些有害影响通过一种辐射防护剂得到了部分缓解。我们的研究结果表明，生物工程构建的唾液腺球体提供了一个可扩展且通用的平台，在疾病建模和药物测试方面具有巨大潜力，从而加速了针对辐射诱导口干症的靶向治疗的开发。
