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

在个体化国家，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下，可引起腺组织纤维化、脂肪变性和分泌唾液的腺泡细胞萎缩。唾液的产生与辐照剂量和暴露于辐射场的腺体体积有关。目前放射性口干症的治疗包括使用唾液代用品和唾液制剂。基于组织工程原理，探讨工程化人唾液腺组织治疗唾液腺功能减退的可行性。原代培养细胞寿命有限主要有两种机制。一种是基于端粒的衰老，另一种是不依赖端粒的衰老，它们被认为是由Rb/p16和p53途径控制的。为了阐明正常唾液腺细胞的再生，我们建立了用非病毒人基因（突变Cdk4、cyclin D1和hTERT）转导的永生化人唾液腺上皮细胞（hSalEC）。通过Cdk4和cyclinD1的转导与hTERT的结合，我们建立了新的hSalEC细胞系。这是首次成功建立hSalEC细胞永生化的报道。

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.