Successful urine excretion strategy allows stem cell-generated embryonic kidneys to function in animals

Written by Alexandra Thompson

Researchers in Japan have developed a method that allows lab-grown kidneys to successfully excrete urine, solving the issue that was hindering the longevity of these organs, which were otherwise functioning correctly, and bringing the possibility of solving organ shortage for transplantation one step closer

Kidneys have several functions, such as regulating blood pressure and removing waste products from the blood. Kidney failure can result in symptoms from lethargy to sudden death. People with renal failure can undergo dialysis, but there are limits to how long it can continue, and unless patients with end-stage renal kidney disease receive a kidney transplant — not always likely owing to a shortage of organs — they require dialysis for the rest of their life.

Researchers at Jikei University School of Medicine (Japan) have successfully grown a kidney from human stem cells in the lab that successfully integrated into rats and pigs, and grew and functioned properly. “Worldwide, the number of patients with end-stage renal disease requiring renal replacement therapy is increasing because of the shortage of donor organs,” the researchers wrote in the study. “We have successfully generated functional kidneys from human stem cells using the organogenic niche method.”

Although they were able to grow functioning organs, they had to create a solution for the kidneys being unable to excrete the urine they were producing: work had previously been carried out to generate functional whole kidneys from stem cells, but no groups succeeded in creating a pathway for the kidneys to send the urine they kidneys created to the bladder for excretion.

The team grew a section of pig kidney using cells (or metanephroi) from an embryonic pig fetus in the lab, which could grow and generate urine. Next, they managed to construct a pathway for urine to travel from the lab-grown kidney out of the body in rats by developing rat metanephroi with bladders that had been developed from cloacas. Once the kidneys were implanted in rats, the cloaca-derived bladders were connected the animal’s actual bladder, allowing urine to leave the body. The method was then carried out in pigs, where the kidneys functioned and grew, and the animals were able to urinate. They called this a ‘stepwise peristaltic ureter’.

Chris Mason, a professor at University College London (UK) commented to the BBC that it was “an interesting step forward … The science looks strong and they have good data in animals. But that’s not to say this will work in humans. We are still years off that. It’s very much mechanistic. It moves us closer to understanding how the plumbing might work.” Although the researchers admit they are years away testing this in humans, this research showing the proper function in an
animal is a significant step forward.

Source: Yokotea S, Matsunarib H, Iwai S. Urine excretion strategy for stem cell-generated embryonic kidneys. PNAS doi:10.1073/pnas.1507803112 (2015);;