Development of the NephroPlate: A high-throughput kidney-on-a-chip platform for identifying chronic kidney disease therapies

Project Summary With chronic kidney disease (CKD) on the rise, it is imperative that we identify better treatment strategies to avoid a healthcare crisis. Current therapeutic interventions address patient symptoms rather than the underlying cause and thereby do not substantially slow disease progression. The development of kidney specific drugs has been hampered by the lack of in vitro kidney models used in the drug development pipeline. Thus, an in vitro model which accurately recapitulates kidney function in the presence and absence of disease-specific stressors is urgently needed to identify targeted CKD interventions. This Phase I SBIR is a collaborative effort between MIMETAS and Children’s Hospital of Los Angeles/University of Southern California (CHLA/USC) which will focus on addressing the market need for a 3D kidney-on-a-chip platform, called the NephroPlate for use in drug discovery. The NephroPlate will enable the evaluation of kidney function in response to serum from patients with CKD in all primary cell types (podocytes, glomerular endothelial cells, renal proximal tubule epithelial cells, non- glomerular endothelial cells). We will characterize the viability, phenotype, and function (glomerular filtration and proximal tubule reabsorption) in both male and female-derived co-cultures by measuring the passage of TRITC- albumin and fluorescent glucose (2-NDBG) within the microfluidic system. We will also validate the drug screening compatibility of the NephroPlate, using standard of care treatments. Resultant filtrate will be evaluated by proteomics. This Phase I SBIR study will demonstrate the feasibility of using the OrganoPlate to support the function of primary kidney cells and mimic both glomerular and proximal tubular function in a 3D co-culture platform. Specifically, this work will provide a foundation for Phase II SBIR and follow on research and development to optimize a platform for novel therapy identification in CKD drug discovery groups.Project Narrative MIMETAS will develop the NephroPlateTM high-throughput platform which will enable a sustainable increase in the number of kidney-specific treatment options for patients with chronic kidney disease (CKD) by offering a more realistic model of the human kidney for in vitro drug screening. The NephroPlate will be used in drug discovery to screen for underlying disease-targeted treatment options for CKD. Ultimately, the result will be a population of patients with a wider selection of therapeutic drugs available to them who will no longer be exposed to agents that allow CKD progression.