HORMONAL PRODUCTION BY CULTURED RENAL CELLS

描述（改编自申请人的摘要）：两个 技术有望为临床提供新的治疗方法， 在乎 在低剪切、随机重力下培养胰岛 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， 免疫避难所。 糖尿病患者的单次腹腔内植入 结果是正常的两年。 该小组对 这种新的激素输送系统的潜在应用，基于 分化的细胞聚集体的腹膜植入， 递送肾激素1-25-二羟基维生素D3和促红细胞生成素。 的 维生素D的一种形式，在维持和保护骨骼完整性方面具有活性， 1-25-维生素D3。 最初确定为透析不足 患者，维生素D现在被认为是调解更常见的问题， 类固醇引起的骨质疏松和年龄引起的骨质减少。 红细胞生成素是 用于治疗终末期肾病贫血、艾滋病和某些形式的 癌 假设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允许替代疗法 通过将细胞聚集体植入缺乏的腹膜腔， 动物 第一种方法是优化细胞培养条件， 荷尔蒙的产生已经被这个实验室证明了。 的 第二种方法是剖析遗传表达的机制， 比较在旋转壁容器培养物中有和没有 重新引入剪切应力。 最后，研究人员将测试是否 移植肾细胞团恢复大鼠的激素活性 通过5/6肾切除术导致肾功能缺陷。 因此，本申请 旨在通过应用新的三维组织培养来推广新技术， 激素替代品的生理调节递送技术 疗法

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.