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.

Chronic kidney disease is a major public health concern, affecting over 37 million people in the US. In this project, we will develop a bioengineered system for modeling kidney filtration function in the lab. The ultimate goal of this project is to develop an innovative tool for testing the toxicity and therapeutic potential of new drugs that target the kidney.