March 14, 2019

Reprogramming cells for kidney repair

Using gene transfer technologies to reprogram adult human kidney cells could lead to novel therapies for chronic kidney disease.

by Kelsey Herbers

Chronic kidney disease is on the rise worldwide. Approaches to develop regenerative or cellular therapies are hindered by the complex cellular structure of the kidney, which is composed of about 1 million microscopic “filters” called nephrons.

Lauren Woodard, PhD, and Matthew Wilson, MD, PhD, at Vanderbilt, in collaboration with Jessica Vanslambrouck, PhD, and Melissa Little, PhD, at Murdoch Children’s Research Institute, among other colleagues, have discovered a way to reprogram adult human kidney cells into induced nephron progenitor-like cells similar to those that form in the kidney during embryonic development. The researchers used a piggyBac transposon to express three transcription factors (SNAI2, EYA1, SIX1) for reprogramming.

The resulting induced nephron progenitor-like cells contributed to the formation of new nephrons in vitro, ex vivo (in a kidney “organoid” derived from induced pluripotent stem cells) and in vivo (in developing mouse kidneys). The direct reprogramming technique, reported in Kidney International, could lead to novel therapies for kidney disease.

This research was supported in part by the National Institutes of Health (grants DK060445, DK114809, DK093660), the Department of Veterans Affairs, a fellowship from Dr. and Mrs. Harold Seltzman, and the Vanderbilt Center for Kidney Disease.