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Design of the Glomerulus and bOwman cApsuLe on a chip (GOAL)

芯片上肾小球和鲍曼胶囊的设计（目标）

基本信息

批准号：
10810038
负责人：
Mira Krendel
金额：
$ 43.5万
依托单位：
UPSTATE MEDICAL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-21 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10810038
关键词：
3-Dimensional 3D Print Ablation Acute Affect Architecture Basement membrane Biological Models Biomedical Engineering Blood capillaries Bowman&apos s space Cell Adhesion Cell Culture System Cell Differentiation process Cell physiology Cells Chronic Kidney Failure Coculture Techniques Collagen Type IV Collection Complex Cues Cytoskeleton Dependence Development Dialysis procedure Diameter Differentiation Antigens Dimensions Disease Disease model Drug Screening Electron Microscopy Endothelial Cells Endothelium Environment Extracellular Matrix Extracellular Matrix Proteins Filtration Foot Process Functional disorder Funding Gel Genetic Genetic Models Genetic Transcription Geometry Glomerular Capillary Glomerular capsule structure Goals In Vitro Injury Kidney Knockout Mice Lasers Liquid substance Measures Mediating Microfluidic Microchips Microfluidics Modeling Molds Morphology Mus National Institute of Diabetes and Digestive and Kidney Diseases Nephrosis Pattern Perfusion Permeability Persons Physiological Physiology Printing Process Property Proteins Proteinuria Proteomics Public Health Pulsatile Flow Puromycin Aminonucleoside Renal Replacement Therapy Renal corpuscle structure Renal glomerular disease Role Shapes Side Soman Specialized Epithelial Cell Structure Study models Supporting Cell Surface System Techniques Technology Testing Therapeutic Thick Thinness Time Study Tissues Toxicity Tests Waste Products Work capsule cell growth cell type design extracellular fluid flow glomerular basement membrane glomerular endothelium glomerular filtration high risk improved in vivo innovation light microscopy meter multi-photon new therapeutic target next generation novel podocyte pressure response slit diaphragm technology development tool tool development

项目摘要

Loss of normal glomerular organization and selective glomerular filtration is one of the key causes of chronic kidney disease, which often leads to the life-long need for renal replacement therapies such as dialysis. Recreating glomerular filtration process in the lab is a challenging undertaking that requires reproducing the complex glomerular architecture and fluid flow patterns and populating the system with the specialized glomerular cell types, including podocytes and endothelial cells. In the proposed work we combined multiphoton laser ablation with 3D printed microfluidic devices to create a microfluidic glomerular model that reproduces the complex network of glomerular capillaries within the hollow space (Bowman’s space) of the renal corpuscle capsule (Bowman’s capsule). The Glomerular-BOwman’s CapSule system on the chip (GOAL-chip) will be populated with podocytes and endothelial cells and tested for the ability to support cell growth and differentiation and selective filtration under the conditions of physiologically relevant filtration pressure and fluid perfusion. In Aim 1, we will determine whether introducing complex capillary topology and appropriate fluid flow rates promotes podocyte differentiation and functionality. In Aim 2, we will use podocyte-endothelial cell coculture within the GOAL-chip and model diseases such as genetic glomerular disorders and acute podocyte injury.

正常肾小球组织的丧失和选择性肾小球滤过是关键之一慢性肾脏疾病的原因，这往往导致终生需要肾脏替代透析等治疗方法。在实验室重建肾小球滤过过程是一项具有挑战性的工作这项工作需要复制复杂的肾小球结构和液体流动模式并使用特殊的肾小球细胞类型填充系统，包括足细胞和内皮细胞。在拟议的工作中，我们结合了多光子激光消融使用3D打印的微流体设备创建复制的微流体肾小球模型肾小球毛细血管在肾小球腔(鲍曼氏间隙)内的复杂网络肾小体胶囊(鲍曼胶囊)。肾小球-鲍曼囊系统芯片(目标芯片)将植入足细胞和内皮细胞，并进行测试支持细胞生长和分化的能力以及在以下条件下的选择性过滤生理上相关的过滤压力和液体灌注量。在目标1中，我们将确定引入复杂的毛细管拓扑结构和适当的流体流速是否会促进足细胞分化和功能。在目标2中，我们将使用足细胞-内皮细胞目标芯片内的共培养和模型疾病，如遗传性肾小球疾病和急性足细胞损伤。