Salivary Stem Cell Identification for Tissue Restoration

用于组织修复的唾液干细胞鉴定

• 批准号: 6685839
• 负责人: CHIH-KO YEH
• 金额: $ 18.25万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6685839
• 关键词: biomarker; biotechnology; cell differentiation; cell proliferation; clinical research; flow cytometry; green fluorescent proteins; human tissue; hyperplasia; hypertrophy; isoproterenol; northern blottings; oral facial restoration; polymerase chain reaction; regeneration; salivary glands; stem cell transplantation; stem cells; tissue /cell preparation; tissue engineering

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.

描述（由申请人提供）：每年30,000-40,000名新的头颈癌患者在放射治疗后永久失去其唾液腺组织。 在美国，另外1-200万人患有Sjogren综合征，这是一种自身免疫性疾病，会导致不可逆的唾液实质组织破坏。 这些患者通常患有严重的口腔疾病，其生活质量受到极大损害。 潜在的治疗方法是使用干细胞在受损组织中的新组织再生或重建腺体或模拟组织以替代被破坏的组织。 为了鉴定唾液腺组织中的干细胞，将在（1）人类唾液组织中检查潜在的干细胞生物标志物的表达，（2）用异丙肾上腺素刺激的大鼠唾液腺的增殖组织，一种β-肾上腺肾上腺素能受体激动剂，（3）在倾向的人类综合和（3）的倾向恢复（3）的结合（3）细胞系（AIM L）。 这些生物标志物包括蛋白质分子与其他器官中的早期唾液腺发育和常见的干细胞标记有关。 唾液腺组织的潜在干细胞标记将由干细胞标记，细胞增殖指标和唾液腺分化标记的共定位确定。 在下一步（AIM 2）中，将从养生的人和大鼠细胞中分离出干细胞群体从唾液腺外植体生长出来。 这些潜在的干细胞以及细胞系将被移植到导管阻塞引起的萎缩性唾液腺中。 移植细胞的生长和分化将通过绿色荧光蛋白可视化。 将监测干细胞的形态组织和干细胞的表达和分化标记物。唾液腺内干细胞的鉴定是将这些细胞分离以再生新组织并重建人造唾液腺的第一步。 该应用的影响不仅在唾液组织工程中，而且还用于理解唾液腺肿瘤的起源和发育。 这些研究的结果最终将导致革命性的唾液腺疾病治疗。