An in-vitro model of the Glomerulus

Introduction and Aims: The Glomerulus is the filtration unit of the kidney. It permits retention of high molecular weight proteins in circulation whilst allowing passage to water, small molecules/proteins, sugars and electrolytes. The selective barrier within the glomerulus is called the glomerular filtration barrier (GFB), a tri-layer structure comprised of a layer of glomerular endothelial cells (GEnCs), a layer of specialised epithelial podocytes and the glomerular basement membrane (GBM) which is situated between the two.

The Glomerulus is formed by (and is the site of) significant intracellular crosstalk. Our lab has established cell lines of conditionally immortalised podocytes and GEnCs, which have been co-cultured using a transwell system. Intracellular crosstalk is however very much a three-dimensional process and as such, an accurate in-vitro model of the glomerulus must co-culture cells on a 3D platform if possible. A 3D model of the glomerulus will also provide a more physiologically-relevant platform to model Glomerulosclerosis and will therefore prove to be a powerful tool for screening therapeutic compounds.

Methods: The focus of ongoing work is to establish an in-vitro 3D model of the Glomerulus through co-culturing the relevant cell types. So far this has included the 3D co-culture of conditionally immortalised podocytes and conditionally immortalised GEnCs using magnetic levitation platforms as well as novel approaches to electrospun poly-glycolic acid scaffold culture.

Results: Results thus far have demonstrated evidence of self-assembly of an organised 3D, multi cell-type structure across a variety of 3D culture platforms.

Conclusions: Once a representative 3D model of the glomerulus is established the aim is to induce glomerulosclerosis in this model and ultimately use it to screen disease-modifying compounds.