Sobue Takanori, Bertolini Martinna, Thompson Angela, Dongari-Bagtzoglou Anna
Department of Oral Health and Diagnostic Sciences, University of Connecticut School of Dental Medicine, Farmington, CT, USA.
Bio Protoc. 2019 Nov 5;9(21):e3411. doi: 10.21769/BioProtoc.3411.
Oral mucositis is a common complication of cancer chemotherapy treatment. Because of the lack of relevant oral mucositis experimental models, it is not clear how chemotherapeutic agents injure the oral mucosa and if commensal microorganisms accelerate tissue damage. We developed an organotypic oral mucosa model that mimics cellular responses commonly associated with cytotoxic chemotherapy. The organotypic model consists of multilayer oral epithelial cells growing over a collagen type I matrix, with embedded fibroblasts. Treatment of organotypic constructs with the chemotherapeutic agent, 5-fluorouracil (5-FU), leads to major histopathologic changes resembling mucositis, such as DNA synthesis inhibition, increased apoptosis and cytoplasmic vacuolation. formed mucosal biofilms on these tissues and augmented the inflammatory responses to 5-FU. This model can be used in further mechanistic studies of oral mucositis and associated opportunistic infections.
口腔黏膜炎是癌症化疗治疗的常见并发症。由于缺乏相关的口腔黏膜炎实验模型,目前尚不清楚化疗药物如何损伤口腔黏膜,以及共生微生物是否会加速组织损伤。我们开发了一种器官型口腔黏膜模型,该模型可模拟通常与细胞毒性化疗相关的细胞反应。该器官型模型由生长在I型胶原基质上的多层口腔上皮细胞和嵌入的成纤维细胞组成。用化疗药物5-氟尿嘧啶(5-FU)处理器官型构建体,会导致类似黏膜炎的主要组织病理学变化,如DNA合成抑制、细胞凋亡增加和细胞质空泡化。在这些组织上形成黏膜生物膜,并增强了对5-FU的炎症反应。该模型可用于口腔黏膜炎及相关机会性感染的进一步机制研究。