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）

• 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
• 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' 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

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.

正常肾小球组织和选择性肾小球滤过功能的丧失是 慢性肾脏疾病的原因，这往往导致终身需要肾脏替代品 治疗方法，如透析。在实验室中重建肾小球滤过过程是一项具有挑战性的工作。 需要复制复杂的肾小球结构和液体流动的任务 模式和填充系统与专门的肾小球细胞类型，包括 足细胞和内皮细胞。在拟议的工作中，我们结合多光子激光烧蚀 用3D打印的微流体设备来创建微流体肾小球模型， 肾小球毛细血管的复杂网络内的中空空间（鲍曼的空间）的 肾小体囊（Bowman囊）。肾小球-鲍曼囊系统 芯片（GOAL芯片）将填充足细胞和内皮细胞，并检测 在以下条件下支持细胞生长和分化以及选择性过滤的能力： 生理相关的滤过压和液体灌注。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 在GOAL-芯片和模型疾病如遗传性肾小球疾病内共培养， 急性足细胞损伤