MECHANISMS OF SALIVARY GLAND DEVELOPMENT

我们相信，如果干细胞活动的潜在机制， 小鼠下颌下腺的发育和正常分泌细胞更新 腺可以理解，那么最终的治疗生物疗法 可能会出现唾液腺功能障碍。 干细胞 下颌下腺的闰管有可能提供 成熟腺体的两种主要分泌细胞类型：腺泡细胞 细胞和颗粒管细胞。 维持和调节的机制 干细胞在基本管状结构的约束下发挥功能 唾液腺实质的形态尚不清楚。 我们假设 细胞保持在发育阶段，原始分化， 表皮生长因子（EGF）是调节其进程的工具。 此外，我们认为，与性别有关的差异，在流通 EGF对干细胞生长的影响 部分原因是在成年人中看到的明显的性别二型性， 腺。 我们还认为，成熟的分泌薄壁组织的丧失， 随着年龄的增长，假定的中间细胞的积累代表了一种 干细胞功能的中断与年龄相关的 EGF水平下降 原分化阶段的特征是存在低水平的 细胞类型特异性分泌蛋白及其同源mRNA水平 在细胞学上未分化的细胞中。 因此， 证实了新生儿中干细胞的原始分化性质， 下颌下腺是为了显示闰管细胞注定要 在青春期产生颗粒管细胞，单独含有 神经生长因子（NGF）及其转录物的种类， 颗粒管细胞表型 对于那些继续进入 成年后，我们打算证明这些干细胞单独含有 低水平的腺泡细胞和颗粒管细胞特异性 多肽、粘蛋白和NGF。 EGF的作用 从后代的增殖和分化模式进行评价 通过持续向成年女性体内注入EGF， 阉割成年雄性。 最后，我们打算表明， 分泌薄壁组织随衰老而衰退并不是因为缺少茎 干细胞及其后代的细胞增殖和分化 将在成熟和衰老的成年人中进行比较。 时代的复兴- EGF补充剂对干细胞生产力的影响 为自己的参与提供证据。

We believe that if the mechanisms underlying stem cell activity in development and normal secretory cell turnover in mouse submandibular gland can be understood, then ultimately a bio-therapy for treatment of salivary gland dysfunction may be developed. Stem cells in the intercalated ducts of the submandibular gland have the potential to give rise to the two main secretory cell types of the mature gland: acinar cells and granular duct cells. The mechanisms maintaining and regulating stem cell function within the constraints of the basic tubular structure of salivary gland parenchyma are not known. We hypothesize that the stem cells ar held at the developmental stage, protodifferentiation, and that epidermal growth factor (EGF) is instrumental in regulating their course. Furthermore, we believe that the gender-related difference in circulating levels of EGF influences stem cell productivity sufficiently to be partially responsible for the overt gender dimorphism seen in the adult gland. We also suggest that the loss of mature secretory parenchyma nd accumulation of putative intermediate cells with aging represents an interruption in stem cell function that is linked with the age-related decline in EGF levels. The protodifferentiated stage is characterized by the presence of low levels of cell type-specific secretory protein and its homologous mRNA in cytologically undifferentiated cells. Thus the strategy for validating the protodifferentiated nature of stem cell sin the neonatal submandibular gland is to show that intercalated duct cells destined to give rise to granular duct cells at puberty, individually contain the species of nerve growth factor (NGF) and its transcript indicative of the granular duct cell phenotype. For stem cells which continue into adulthood, we intend to show that these stem cells individually contain low levels of both acinar cell and granular duct cell-specific polypeptides, mucin and NGF respectively. The role of EGF will be evaluated from patterns of proliferation and differentiation of progeny of the stem cells by continuously infusing EGF into adult females and castrate adult males. Finally, we intend to show that the overall decline with aging in secretory parenchyma is not due to a lack of stem cell proliferation and differentiation of stem cells and their progeny will be compared in mature and senescent adults. Reversal of the age- related changes in stem cell productivity by EGF supplementation will provide evidence for its involvement.