Establishment of immortalized normal salivary glands epithelial cells and regeneration of salivary gland for post-irradiation

永生化正常唾液腺上皮细胞的建立及辐照后唾液腺的再生

• 批准号: 19592331
• 负责人: NOGUCHI Kazuma
• 金额: $ 2.75万
• 依托单位: Hyogo College of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19592331/
• 关键词: 唾液腺; 放射線; 口腔乾燥; 再生医療

In individualized countries the majority of patients with head and neck cancer are treated with radiation therapy. Exposure of the major salivary glands to the ionizing radiation induced fibrosis fatty degeneration of the gland tissue and atrophy of the saliva-producting acinar cells. Saliva production is decreased in correlation with the irradiation dose and the gland volume exposed to the radiation field. Current management of radiation induced xerostomia includes the administration of saliva substitutes and sialogogues. Based on the principles of tissue engineering, we investigated the feasibility of engineering human salivary gland tissue for the treatment of salivary gland hypofunction. There are two major mechanisms that cause the limited life span of primary culture cells. One is the telomere-based senescene, and the other is telomere-independent senescene, which is thought to be controlled by the Rb/p16 and p53 pathways. To elucidate the regeneration of normal salivary gland cell, we established immortalized human salivary gland epithelial cell (hSalEC)s transduced with non-viral human gene (mutant Cdk4, cyclin D1, and hTERT). By Cdk4 and cyclinD1 transduction in combination with hTERT, we here established novel hSalEC cell line. This is a first report of successful establishment of hSalEC cells immortalization.

在个别国家，大多数头颈癌患者接受放射治疗。大唾液腺暴露于电离辐射引起腺体组织纤维化、脂肪变性和分泌唾液的腺泡细胞萎缩。唾液分泌减少与辐射剂量和暴露于辐射场的腺体体积相关。目前的管理辐射引起的口干症包括管理唾液替代品和唾液。本研究以组织工程学原理为基础，探讨组织工程化人涎腺组织用于治疗涎腺功能减退症的可行性。有两种主要机制导致原代培养细胞的寿命有限。一种是基于端粒的衰老，另一种是端粒非依赖性衰老，这被认为是由Rb/p16和p53通路控制的。为了研究正常涎腺细胞的再生机制，我们建立了转人非病毒基因（突变型Cdk 4、cyclin D1和hTERT）的永生化人涎腺上皮细胞（hSalEC）。通过Cdk 4和cyclinD 1的联合转导和hTERT的作用，我们建立了一种新的hSalEC细胞系。这是首次成功建立hSalEC细胞永生化的报道。