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

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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.