Modeling diabetes using an integrated plate system
使用集成板系统模拟糖尿病
基本信息
- 批准号:10229625
- 负责人:
- 金额:$ 157.8万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-09-20 至 2023-07-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Summary: Modeling Diabetes in an Integrated Plate System
The control of nutrient homeostasis involves the cross talk between multiple organ systems including the
gastrointestinal tract, liver, endocrine pancreas, and nervous system, among others. Eating, digestion and
nutrient absorption trigger a number of downstream effects on the liver and pancreas that are mediated by
nutrients and GI hormones. Type 2 diabetes (T2D) is a metabolic disease that involves all of these organ
systems. The most effective cure for T2D is gastric bypass surgery, which is invasive and has complications,
but results in improved beta cell function and reversal of insulin resistance in the liver. It is not known why
surgery is curative, however the changes in GI hormones that accompany this reversal of T2D are believed to
contribute. Current efforts to study the interplay between liver, pancreas and the GI tract have depended on
animal models, which often do not recapitulate human physiology. Moreover due to the inter-organ effects of
systemic factors like hormones and nutrients, it is challenging to separate direct vs indirect effects on organ
systems in vivo. This proposal aims to develop a tractable, high throughput fluidic system containing human
pluripotent stem cell (PSC)-derived liver, pancreas and intestine to study inter-organ crosstalk, to identify
mechanisms involved in reversal of T2D, and to develop a high throughput-screening platform for basic
research and therapeutic screening purposes.
Aim 1: Develop integrated plate systems that can support organoid function and communication.
Manufacture and deliver 36PillarPlate system (UG3) 384PillarPlate (UH3) systems.
Aim 2: Synthesize tunable hydrogels for robust and reproducible organoid growth and function. Identify
biomimetic hydrogels that support the short-term growth of liver, intestinal and pancreatic tissues (UG3) and
support organoid function and growth for 4 weeks (UH3).
Aim 3: Establish liver, intestine, and pancreas organoids in the integrated plate system.
Incorporate and test individual organoid systems for function on 36PillarPlate (UG3) 384-well micropillar
platform (UH3). Test for organ function and crosstalk for up to 4 weeks.
Aim 4: Validate the integrated plate system with known therapeutics for T2D (UH3 only).
摘要:在集成板系统中对糖尿病进行建模
营养稳态的控制涉及多个器官系统之间的串扰
胃肠道,肝脏,内分泌胰腺和神经系统等。进食,消化和
营养吸收引发了许多下游对肝脏和胰腺的影响,这些影响是由
营养和胃肠道激素。 2型糖尿病(T2D)是一种代谢疾病,涉及所有这些器官
系统。 T2D最有效的治疗方法是胃搭桥手术,它具有侵入性并且具有并发症,
但是导致肝脏抗性的β细胞功能和胰岛素抵抗的逆转。不知道为什么
手术是治愈性的,但是T2D逆转的GI激素的变化被认为是
贡献。当前研究肝脏,胰腺和胃肠道之间的相互作用的努力取决于
动物模型,通常不会概括人类生理。而且,由于器官间影响
诸如激素和养分之类的系统性因素,将直接与间接影响分开对器官的影响是一项挑战
体内系统。该提案旨在开发一个可进行的,高通量的流体系统,其中包含人类
多能干细胞(PSC)衍生的肝脏,胰腺和肠道肠间串扰,以识别
T2D逆转涉及的机制,并为基本的高吞吐量平台开发
研究和治疗性筛查目的。
目标1:开发可以支持器官功能和通信的集成板系统。
制造和交付36板块系统(UG3)384板块(UH3)系统。
AIM 2:合成可调水凝胶,以实现健壮和可再现的器官生长和功能。确认
支持肝脏,肠道和胰腺组织(UG3)和
支持器官功能和生长4周(UH3)。
AIM 3:在集成的板系统中建立肝脏,肠和胰腺器官。
在36板块(UG3)上合并并测试单个器官系统,以进行功能(UG3)384孔微柱
平台(UH3)。测试器官功能和串扰长达4周。
AIM 4:用已知的T2D疗法(仅UH3)验证集成板系统。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
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数据更新时间:2024-06-01
MOO-YEAL LEE的其他基金
Modeling diabetes using an integrated plate system
使用集成板系统模拟糖尿病
- 批准号:1047432810474328
- 财政年份:2018
- 资助金额:$ 157.8万$ 157.8万
- 项目类别:
Modeling diabetes using an integrated plate system
使用集成板系统模拟糖尿病
- 批准号:1021638810216388
- 财政年份:2018
- 资助金额:$ 157.8万$ 157.8万
- 项目类别:
Mechanistic Study of Developmental Neurotoxicity on 3D Cultured Stem Cell Microarrays
3D 培养干细胞微阵列的发育神经毒性机制研究
- 批准号:89446048944604
- 财政年份:2015
- 资助金额:$ 157.8万$ 157.8万
- 项目类别:
Mechanistic Study of Developmental Neurotoxicity on 3D Cultured Stem Cell Microarrays
3D 培养干细胞微阵列的发育神经毒性机制研究
- 批准号:92986629298662
- 财政年份:2015
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TeamChip for High-Throughput, Predictive Human Metabolism and Toxicology: Phase I
用于高通量、预测性人体代谢和毒理学的 TeamChip:第一阶段
- 批准号:82514568251456
- 财政年份:2010
- 资助金额:$ 157.8万$ 157.8万
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TeamChip for High-throughput, Predictive Human Metabolism and Toxicology
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A High-Throughput Human Metabolic Stability Assay Chip for Early-Stage Drug Disco
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- 资助金额:$ 157.8万$ 157.8万
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