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

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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