MODEL B CELLS FOR USE IN DIABETES TREATMENT

用于糖尿病治疗的 B 型细胞

• 批准号: 2377810
• 负责人: IOANNIS CONSTANTINIDIS
• 金额: $ 10.81万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-03-01 至 2000-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2377810
• 关键词: alginates; artificial endocrine pancreas; bioenergetics; blood glucose; brain metabolism; disease /disorder model; glycosuria; hypoxia; laboratory rat; nonhuman therapy evaluation; nuclear magnetic resonance spectroscopy; pancreatic islets; streptozotocin; tissue /cell culture; tissue engineering

Transplantation of islets or Beta-cells offers a realistic possibility for physiological control of blood glucose in diabetics. All reports agree that euglycemia can be achieved for a limited time period (less than 1 year) following transplantation. A major limitation to using normal islets or Beta-cells in implantable bioartificial pancreata is availability. Normal cells isolated from mammalian glands exhibit littl growth, and rapidly lose their differentiated properties in culture. With an estimated 300,000 cases of insulin dependent diabetes mellitus and an additional 30,000 new cases per year in the USA, alone, the deman for islets would be enormous. Consequently, cell lines which retain in culture the differentiated properties of normal islets in vivo are neede for the development of a bioartificial pancreas. Since all living systems need energy to sustain their life and function, knowledge about their energy metabolism as it responds to expected physiologic changes is crucial in assessing the viability and function of these bioartificia devices. In this application, we propose to study the bioenergetic stability of the continuous Beta cell line, BetaTC3, in an immunoprotected environment under repetitive glucose stimulations and hypoxic stresses. Furthermore, we will implant immunoprotected BetaTC3 cells in streptozotocin-induced diabetic rats, and investigate their ability to restore glucose regulation in these animals. This type of information is currently unavailable, and will add greatly to the understanding of the capabilities and limitations of an implantable bioartificial pancreas. We propose to use the non-invasive modality of Nuclear Magnetic Resonance spectroscopy, for both in vitro and in vivo studies. 31P NMR will assess intracellular levels of high and low energ phosphates, and 13C NMR will determine the relative fluxes through glycolysis and the tricarboxylic acid cycle. Enzymatic assays of the perfusion medium effluent, perchloric acid extract of the cells, and histologic examinations of the beads will be performed in support of the in vitro studies. Changes in tissue biochemistry and key physiological parameters including blood glucose and insulin levels will be monitored to assess the success of the implant. This proposal is the beginning of an interdisciplinary project that has brought together expertise from engineering, chemistry, physics and medicine. Our long range goal is to develop a clinically useful implantable bioartificial pancreas for the treatment of diabetes mellitu in human patients.

胰岛或β细胞的移植提供了现实的可能性 用于糖尿病患者血糖的生理控制。 所有报告 同意可以在有限的时间段内实现尤利西亚（更少） 移植后比1年）。 使用的主要限制 可植入的生物人工胰腺中的普通胰岛或β细胞是 可用性。 从哺乳动物腺分离出的正常细胞表现出littl 生长，并迅速失去其在培养中的差异化特性。 估计有30万例胰岛素依赖性糖尿病 仅在美国，每年再有30,000个新案件 因为胰岛将是巨大的。 因此，保留在 培养体内正常胰岛的分化特性是需要的 为了开发生物人工胰腺。 自从所有生活 系统需要能量来维持其生活和功能，了解 他们的能量代谢对预期的生理变化做出反应 对于评估这些生物学症的生存能力和功能至关重要 设备。 在此应用中，我们建议研究生物能 连续Beta细胞系Betatc3的稳定性 在重复性葡萄糖刺激下进行免疫保护环境和 低氧应激。 此外，我们将植入免疫保护物的betatc3 链蛋白酶诱导的糖尿病大鼠中的细胞，并研究其 能够恢复这些动物中的葡萄糖调节。 这类 当前信息目前不可用，将大大增加 了解可植入的能力和局限性 人工胰腺。 我们建议使用非侵入性方式 用于体外和体内的核磁共振光谱 研究。 31p NMR将评估细胞内高能量和低能量 磷酸盐和13C NMR将确定通过 糖酵解和三羧酸周期。 酶促测定 灌注培养基废水，细胞的高氯酸提取物，以及 将对珠子进行组织学检查以支持 体外研究。 组织生物化学和关键生理的变化 将监测包括血糖和胰岛素水平在内的参数 评估植入物的成功。 该建议是一个跨学科项目的开始 汇集了工程，化学，物理和 药品。 我们的远距离目标是开发临床上有用的 可植入的生物人工胰腺治疗糖尿病 在人类患者中。