|Kidney bud created from human stem cells (in blue and green). Cells in red are mouse kidney cells. Courtesy of the Salk Institute for Biological Studies|
Over the years scientists have been stymied in their attempts to coax human stem cells -- either embryonic or reprogrammed iPS cells -- into cells of the kidney. The goal had been to generate human kidney cells in a lab dish that could then be used to screen drugs to treat kidney disease. But they cells just didn't want to cooperate.
The team at Salk, led by Juan Carlos Izpisua Belmonte, started out by getting the human stem cells part way down the path to becoming kidney cells. Then, to get the rest of the way, placed the cells in a dish with embryonic mouse kidney cells. Those mouse cells gave the human pre-kidney cells signals they needed to fully develop into the types of three dimensional buds that you'd find in a developing kidney. This work was published in the November 17 Nature Cell Biology.
They took this approach one step further, and created iPS cells from people with a form of kidney disease called PKD. Using their technique, the group coaxed those cells to form kidney buds in a lab dish. These cells provide the first access scientists have had to directly study diseased kidney tissue in a lab dish.
A press release from Salk quotes lead study author Ignacio Sancho-Martinez, a research associate in Izpisua Belmonte's laboratory.
"Our differentiation strategies represent the cornerstone of disease modeling and drug discovery studies. Our observations will help guide future studies on the precise cellular implications that PKD might play in the context of kidney development."This is one of several studies CIRM funds in which scientists are, for the first time, able to study functional human tissue in a lab dish. Now, the scientists can test drugs to improve how the cells function rather than testing the drugs in animals, which in many cases respond to those drugs very differently than humans.
CIRM funding: Yun Xia and Keiichiro Suzuki (TG2-01158)
Xia Y, Nivet E, Sancho-Martinez I, Gallegos T, Suzuki K, Okamura D, Wu MZ, Dubova I, Esteban CR, Montserrat N, Campistol JM, & Belmonte JC (2013). Directed differentiation of human pluripotent cells to ureteric bud kidney progenitor-like cells. Nature cell biology PMID: 24240476