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Glomerulus on-a-Chip: A New Model to Study the Glomerular Filtration Barrier in vitro

Friday, 5 October 2018 at 11:00

Add to Calendar ▼2018-10-05 11:00:002018-10-05 12:00:00Europe/LondonGlomerulus on-a-Chip: A New Model to Study the Glomerular Filtration Barrier in vitro3D-Culture and Organoids in Coronado Island, CaliforniaCoronado Island, CaliforniaSELECTBIOenquiries@selectbiosciences.com

The glomerular filtration barrier has three major components: the podocyte with their slit diaphragm, the glomerular basement membrane (GBM) and the fenestrated endothelial cell: each of them is essential for the correct blood filtration. Damage to any of these components leads to a severe, irreversible disruption of the filtration barrier with onset of chronic damage which can lead to renal failure, requiring dialysis and transplantation. The development of new effective therapeutic approaches is limited by our poor understanding of the complex cell-matrix interactions and cellular cross talk within the filtration barrier in vivo and by the absence of an in vitro model that mimics the glomerular filtration barrier. We developed a system that mimics the complex architecture of the filtration barrier and that can be used to better study glomerular (patho)-physiology is urgently needed. We have recently generated a population of renal progenitors within human amniotic fluid (hAKPC-P) that can differentiate into podocyte-like cells. Taking advantage of the peculiar characteristics of available Organ-on-a-Chip systems, we have developed an innovative Glomerulus-on-a-Chip system by co-culturing hAKPC-P and human glomerular endothelial cells in OrganoplateTM microfluidic plates. Immunostaining and qPCR were performed to characterize the 3D in vitro system We have successfully established the ideal conditions for in vitro co- culture of the hAKPC-P/glomerular endothelial cell within a microfluidic plate up to 21 days. Apoptosis and proliferation were confirmed by TUNEL and PCNA respectively. Vessel formation by glomerular endothelial cells was confirmed along with marked expression of endothelial marker VE-Cadherin while hAKPC-P-derived podocytes were positive for nephrin and podocin. De-novo deposition of collagen IV (essential for proper formation and function of the filtration barrier) in the 3D microfluidic culture system was also confirmed by immunostaining. Our preliminary results suggest the feasibility of Organoplates for the co-culture of podocytes and endothelial cells in a 3D environment that more closely mimics the structure of the glomerular filtration barrier. If successful this system might prove useful for understanding podocytes/endothelial crosstalk (or its perturbations) and how this might affects glomerular homeostasis and, ultimately, will increase our ability to individualize treatment, predict drug susceptibility among patients and avoid unwanted side effects, thus ultimately benefiting patients affected by renal failure.