Development of a Highly Differentiated Human Primary Proximal Tubule MPS Model (aProximate MPS Flow)

We developed a physiologically relevant micro-physiological system (MPS) model of the human PT, the aProximate MPS Flow platform.

In this model, primary human PT cells (hPTCs) are subjected to fluidic media flow and a shear stress of 0.01–0.2 Pa. We observe that these cells replicate the polarity of hPTCs and exhibit a higher expression of all the key transporters of SLC22A6 (OAT1), SLC22A8 (OAT3), SLC22A2 (OCT2), SLC47A1 (MATE1), SLC22A12 (URAT1), SLC2A9 (GLUT9), ABCB1 (MDR1), ABCC2 (MRP2), LRP2 (megalin), CUBN (cubilin), compared with cells grown under static conditions. Immunofluorescence microscopy confirmed an increase in OAT1, OAT3, and cilia protein expression. Increased sensitivity to nephrotoxic protein cisplatin was observed; creatinine and FITC-albumin uptake was significantly increased under fluidic shear stress conditions. Our data suggest that growing human PT cells under media flow significantly improves the phenotype and function of hPTC monolayers and has benefits to the utility and near-physiology of the model.

Our MPS Flow platform is patented (Patent No: G001336.GB) and will be applied to our other in vitro models.