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

在个别化的国家，大多数头颈癌患者都接受放射治疗。将主要唾液腺暴露于电离辐射可引起腺体组织的纤维化、脂肪变性和产生唾液的腺泡细胞萎缩。唾液产量随照射剂量和照射野中腺体体积的增加而减少。目前治疗放射性口干症的方法包括唾液替代品和唾液凝胶剂的应用。根据组织工程学的原理，探讨了将人涎腺组织工程化治疗涎腺功能减退的可行性。导致原代培养细胞寿命有限的主要机制有两个。一种是基于端粒的衰老，另一种是端粒非依赖性的衰老，被认为是由Rb/p16和P53通路控制的。为了阐明正常涎腺细胞的再生，我们建立了非病毒型人基因(突变型CDK4、细胞周期蛋白D1和端粒酶逆转录酶)转基因的永生化人涎腺上皮细胞株S。通过CDK4和Cyclin D1转导结合hTERT，我们建立了新的hSalEC细胞系。这是成功建立hSalEC永生化细胞的首次报道。

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.