Restoring the Renal Extracellular Matrix Using Engineered Growth Factors

Type of Award: Catalyst
Date Awarded: March 2017
Award End Date: February 2018
Amount Awarded: $ 248,299.00
PI(s): Jason Wertheim, NU; Jeffrey Hubbell, UChicago;

Abstract: Far more patients with end-stage kidney disease are waiting for a kidney transplant (>100,000) than the available supply of donor kidneys (<18,000 in 2015), and this shortfall continues to worsen. One novel approach to develop replacement tissues involves removing endogenous cells from an incompatible kidney to produce a three-dimensional (3D) extracellular matrix (ECM) scaffold that can support stem cell differentiation and regeneration of renal tissue. Growth factors signal cells to migrate, proliferate, and differentiate, essential tasks for kidney regeneration, but have not been harnessed for medical applications due to systemic side effects related to escape into the bloodstream. To overcome this limitation, we have engineered growth factors (eGFs) that bind to ECM proteins at the site of administration. We propose to discover new binding sites for eGFs that target specific proteins retained in kidney-derived ECM scaffolds to augment pluripotent stem cell-mediated development of renal tissue.