HORMONAL PRODUCTION BY CULTURED RENAL CELLS

描述(改编自申请者的摘要)：两个词的结合 技术有望为临床提供一种新的治疗方法 关心。低剪切随机重力条件下胰岛的培养 旋转壁血管，通过调节胰岛素维持分化 分泌物。这些胰岛被藻酸盐包裹，以产生非炎症性 免疫天堂。糖尿病患者一次性腹膜腔内植入术 结果两年内血糖正常。该小组对 这种新的激素递送系统的潜在应用，基于 腹膜移植分化的细胞聚集体，以解决 肾激素1-25-二羟基维生素D3和促红细胞生成素的输送。这个 维他命D对保持和保护骨骼完整性有积极作用 1-25-二羟基维生素D3。最初被确认为透析不足 患者，维生素D现在被认为是更常见的 类固醇引起的骨质疏松症和年龄引起的骨量减少。促红细胞生成素是 用于治疗终末期肾病的贫血、艾滋病和某些形式的 癌症。 假说是通过旋转来维持肾脏激素的产生 肾上皮细胞的壁血管培养将使替代疗法成为可能 通过将细胞集合体植入缺陷性腹膜腔 动物。第一种方法是优化细胞培养条件，为 这个实验室已经证明了荷尔蒙的产生。这个 第二种方法是通过分析基因表达的机制 有无旋转壁血管培养的基因表达比较 剪应力的重新引入。最后，调查员将测试 移植肾细胞集合体恢复大鼠激素活性 因5/6肾切除而表现为激素缺乏。因此，此应用程序 旨在通过应用新的三维组织培养来推广新技术 激素替代的生理调节分娩技术 心理治疗。

DESCRIPTION (Adapted from the applicant's abstract): The coalescence of two technologies promises to provide a new therapeutic approach in clinical care. Culture of pancreatic islets in low shear, randomized gravity rotating wall vessels, maintains differentiation with regulated insulin secretion. These islets are alginate coated to create a non-inflammatory immune haven. A single intraperitoneal implantation in diabetic patients results in normoglycemia for two years. This group is interested in the potential application of this new hormonal delivery system, based on peritoneal implantation of differentiated cell aggregates, to the problem of delivery of renal hormones 1-25-diOH vitamin D3 and erythropoietin. The form of vitamin D active in maintaining and protecting bone integrity is 1-25-diOH vitamin D3. Initially identified as deficient in dialysis patients, vitamin D is now thought to mediate the more common problems of steroid induced osteoporosis, and age-induced osteopenia. Erythropoietin is used to treat anemia of end-stage-renal disease, AIDS, and some forms of cancer. The hypothesis is that maintenance of renal hormone production by rotating wall vessel culture of renal epithelial cells will allow replacement therapy by implantation of cell aggregates into the peritoneal cavity of deficient animals. The first approach is to optimize cell culture conditions for the hormonal production that has already demonstrated by this laboratory. The second approach is to dissect the mechanisms of genetic expression by comparing gene expression in rotating wall vessel culture with and without reintroduction of shear stress. Last, the investigator will test whether implantation of renal cell aggregates restores hormonal activity in rats rendered hormonally deficient by 5/6 nephrectomy. Hence, this application aims to extend new technology by applying novel 3-dimensional tissue culture techniques to physiologically regulated delivery of hormonal replacement therapy.