One Cell to Rule Them All : The Potential of Proximal Tubule Epithelial Cells in Regenerative Kidney Therapies for Uremic Toxin Removal

Abstract

The kidney is responsible for the excretion of waste solutes from the blood. In case of kidney failure, dialysis can replace its passive filtration function, but the loss of active secretion leads to the accumulation of >100 nonfilterable waste solutes that slowly intoxicate the body from within. This thesis presents two new concepts for therapies that could replace active secretion by focusing on a specific kidney cell type, the proximal tubule epithelial cells (PTECs). PTECs contain the transport proteins that mediate the active removal of waste products. In the first part of the thesis, we explored molecular pathways that regulate the transporter expression PTECs and thus might be useful for pharmacological intervention. In the second part, we provide proof-of-concept for the fabrication of tubular scaffolds to engineer 3D proximal kidney tubules that can replace active secretion. For clinical treatment, these concepts remain hypothetical, but our work lays the groundwork by revealing a multitude of potential molecular targets and by demonstrating the feasibility of stand-alone graft fabrication.