Development of advanced healthy and diseased in vitro 3D glomerulus model for drug testing and understanding kidney disease mechanisms

开发先进的健康和患病体外 3D 肾小球模型，用于药物测试和了解肾脏疾病机制

• 批准号: 445679257
• 负责人: Professor Dr. Michael Gelinsky
• 金额: --
• 依托单位: Department of Biotechnology
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/445679257?language=en
• 关键词: Development; advanced; healthy; diseased; vitro

Kidney plays an important role in maintaining homeostasis in the body by regulating water, electrolytes, and the acid/base balance. Apart from secreting various hormones, it also plays an important role in regulating red blood cell production and blood pressure. For understanding kidney diseases and for drug testing it would be helpful to have functional in vitro models of the different units of the organ. Whereas a number of models for the proximal tubule have been proposed in the last years only few models for the glomerulus exist – which is the part of the kidney where primary urine is formed. Main problem is to mimic the relatively high internal pressure of capillaries which is relevant for the filtration processes.In this Indo-German project we want to use state-of-the-art additive manufacturing technologies like melt electrowriting to fabricate fibrous tubes which are able to withstand the physiological pressure. The tubes will be coated with components of the extracellular matrix (ECM) of the glomerulus like collagens and laminin and also with decellularised ECM from animal-derived kidney glomeruli. After seeding of the tubes with tissue-specific endothelial cells (lumen) and podocytes (external surface) the structures will be integrated in customised perfusion bioreactors which allow separate perfusion of both internal (tube lumen) and external spaces. Finally, the function and relevance of the model will be tested by applying known drugs.This collaborative project will combine the expertise of both applicants in the fields of biomaterials, tissue engineering and additive manufacturing (Michael Gelinsky, TU Dresden) and extraction from ECM from decellularised tissues and design and manufacturing of customized bioreactor systems (Falguni Pati, IIT Hyderabad).

肾脏通过调节水、电解质和酸碱平衡，在维持体内稳态中起着重要作用。除了分泌各种激素外，它还在调节红细胞生成和血压方面起着重要作用。为了了解肾脏疾病和药物测试，拥有器官不同单元的功能体外模型将是有帮助的。尽管近年来提出了许多近端小管的模型，但针对肾小球的模型却很少，肾小球是肾脏中形成初级尿液的部分。主要问题是模拟相对较高的毛细管内压，这与过滤过程有关。在这个印德项目中，我们希望使用最先进的增材制造技术，如熔融电解，来制造能够承受生理压力的纤维管。这些管将被肾小球的细胞外基质（ECM）成分（如胶原和层粘连蛋白）和动物源性肾小球的脱细胞ECM包裹。在植入组织特异性内皮细胞（管腔）和足细胞（外表面）后，这些结构将被整合到定制的灌注生物反应器中，允许内部（管腔）和外部空间的单独灌注。最后，通过应用已知药物对模型的功能和相关性进行检验。该合作项目将结合双方申请人在生物材料、组织工程和增材制造领域的专业知识（Michael Gelinsky，德国德累斯顿工业大学），从脱细胞组织中提取ECM，设计和制造定制生物反应器系统（Falguni Pati，印度理工学院海德拉巴分校）。