Development of an in vitro model of the glomerular filtration barrier using cell sheet engineering

复杂的体外模型开始为研究复杂器官的特定亚结构表型提供更明确的工具。目前，还没有肾小球的体外模型，其证明了指示该复杂结构内的特定细胞类型的特征范围，或使其能够作为过滤单元发挥功能。虽然细胞系存在，作为单细胞或共培养系统，他们不提供完整的基因型/表型的肾小球滤过单位，也不存在于一个三维architecture.The发展这样一个模型将使研究的基础生物学的肾小球在体外设置和各种类型的细胞如何相互作用，在这个结构，形成一个功能性的过滤屏障。这也将减少研究足细胞/肾小球生物学的动物实验模型的需要。此外，虽然被认为是一个重大的挑战，这样的模型可以使自己与肾单位肾小管培养物相关联，从而能够形成一个完整的体外肾脏模型。该项目的职责是使用3D培养技术、流体/微流体和共培养来模拟肾小球内与肾小球内皮相关的上皮细胞（足细胞）的器官型结构和功能。细胞片工程，一种已经在曼彻斯特大学的小组内建立的技术，将可用于帮助组装模型。成功的候选人将获得宝贵的第一手经验，在建立复杂的体外模型，使用各种显微镜技术，以及肾脏生物学/生理学和病理生理学的深厚背景知识

Complex in vitro models are starting to provide more defined tools for the study of specific substructural phenotypes for complex organs. At present there are no in vitro models of the glomerulus that demonstrate the range of characteristics indicative of the specific cell types within this complex structure, or enable its functionality as a filtration unit. Although cell lines exist, as single cell or co-culture systems, they do not offer the full genotype/phenotype of the glomerular filtration unit, nor do not they exist within a 3-dimensional architecture.The development of such a model would enable the study of the basic biology of the glomerulus in an in vitro setting and how the various cell types interact within this structure to form a functional filtration barrier. This would also reduce the need for animal experimental models to study podocyte/glomerular biology. Furthermore, although recognised as a significant challenge, such a model could lend itself for association with nephron tubular cultures enabling the formation of an integrated in vitro model of the kidney. The remit of the project would be to model the organotypic structure and function of epithelial cells (podocytes) within the glomerulus in association with the glomerular endothelium, using 3D culture technologies, fluidics/microfluidics and co-culture. Cell sheet engineering, a technique already established within the group at the University of Manchester, will be available to aid the assembly of the model. The successful candidate would gain valuable first-hand experience in building complex in vitro models, the use of various microscopy techniques, and a deep background knowledge of kidney biology/physiology and pathophysiology