Salivary Stem Cell Identification for Tissue Restoration

描述（由申请人提供）：每年有30，000 - 40，000名新的头颈癌患者在放射治疗后永久失去唾液腺组织。 在美国，另外1-2百万人患有干燥综合征，这是一种自身免疫性疾病，导致唾液实质组织的不可逆破坏。 这些患者通常患有严重的口腔疾病，他们的生活质量大大降低。 一种潜在的治疗方法是使用干细胞在受损组织中再生新组织，或重建腺体或模拟组织以取代受损组织。 为了鉴定唾液腺组织中的干细胞，将在以下中检查潜在干细胞生物标志物的表达：（1）人唾液腺组织，（2）用异丙肾上腺素（β-肾上腺素能受体激动剂）刺激的大鼠唾液腺的增殖组织，（3）从导管阻塞诱导的变性恢复的大鼠唾液腺中的组织再生，和（4）人和大鼠细胞系（Aim 1）。 这些生物标志物包括与早期唾液腺发育密切相关的蛋白质分子和其他器官中常见的干细胞标志物。 将通过干细胞标志物、细胞增殖指标和唾液腺分化标志物的共定位来确定唾液腺组织的潜在干细胞标志物。 在下一步（目标2）中，干细胞群将从唾液腺外植体生长出来的培养的人和大鼠细胞中分离。 这些潜在的干细胞以及细胞系将被移植到导管阻塞诱导的萎缩唾液腺中。 移植细胞的生长和分化将通过绿色荧光蛋白可视化。 将监测每种细胞类型的干细胞和分化标志物的形态组织和表达。唾液腺干细胞的鉴定是分离唾液腺干细胞用于组织再生和构建人工唾液腺的第一步。 这一应用的影响不仅是唾液腺组织工程，但也为了解涎腺肿瘤的发生和发展。 这些研究的结果将最终导致唾液腺疾病的革命性治疗。

DESCRIPTION (provided by applicant): Each year 30,000-40,000 new head and neck cancer patients permanently lose their salivary gland tissues following radiation therapy. An additional 1-2 million people in US suffer from Sjogren's Syndrome, an autoimmune disease that causes irreversible destruction of salivary parenchymal tissue. These patients usually suffer from severe oral diseases and their quality of life is greatly compromised. A potential treatment is to use stem cells to regenerate new tissue in the damaged tissue or to reconstruct a gland or mimetic tissue to replace the destroyed tissue. To identify the stem cells in salivary gland tissue, the expression of potential stem cell biomarkers will be examined in (1) human salivary tissues, (2) proliferating tissue of rat salivary glands stimulated with isoproterenol, a beta-adrenergic receptor agonist, (3) regeneration of tissue in rat salivary glands recovering from duct obstruction-induced degeneration, and (4) human and rat cell lines (Aim l). These biomarkers include protein molecules critically involved in early salivary gland development and common stem cell markers in other organs. The potential stem cell markers for salivary gland tissue will be determined by the co-localization of stem cell markers, cell proliferation indicators and salivary gland differentiation markers. In the next step (Aim 2), stem cell populations will be isolated from cultured human and rat cells outgrown from salivary gland explants. These potential stem cells as well as cell lines will be transplanted into a duct obstruction-induced atrophic salivary gland. The growth and differentiation of transplanted cells will be visualized by Green Fluorescence Protein. The morphological organization and expression of stem cells and differentiation markers for each cell type will be monitored. Identification of stem cells within salivary glands is first step toward isolation of these cells to regeneration of new tissue and reconstruct an artificial salivary gland. The impact of this application is not only for salivary tissue engineering but also for understanding salivary gland tumor genesis and development. The results of these studies will ultimately lead to revolutionary treatment of salivary gland diseases.