A Jikei University School of Medicine research team based in Tokyo, Japan, led by Takashi Yokoo, in collaboration with scientists from Meiji University and St. Marianna University School of Medicine in Kawasaki, Keio University School of Medicine in Tokyo, and the School of Veterinary Medicine at Kitasato University in Towada, has shown that mini kidneys grown in vitro from human stem cells can be effectively connected to the excretory systems of rats and pigs.
This is not the first time that research groups have successfully grown mini kidneys in the laboratory. However, connecting these laboratory-grown organs to a laboratory animal’s excretory system constitutes a major technical challenge. The Jikei University team used an approach that employs a step-wise peristaltic ureter or SWPU to connect its lab-grown mini kidneys to the ureter of the transplant animal.
Previous attempts to use laboratory-grown kidneys in laboratory animals have failed because while the transplanted kidneys made urine, they were unable to pass that urine to the animal’s bladder and the kidneys swelled up and failed. Yokoo and his collaborators and colleagues used a stem cell method to make their mini kidneys, as others have in the past. However, he and his team grew more than just the kidney for the host animal; that also grew a drainage tube, known as a ureter, as well, in addition to a bladder to collect and store the urine.
Yokoo and others used laboratory rats as the incubators for their growing tissue. When they connected the new kidney and its tubular systems to the animal’s existing bladder, the system worked. Urine passed from the transplanted kidney into the transplanted bladder and then into the rat bladder. The transplant was still working well when they checked eight weeks later. Then Yokoo and others repeated their procedure in pigs, which are larger mammals than rats and better model systems for human beings. Fortunately, they achieved the same results.
Although this technology is still years away from clinical trials with human patients, this work provides a paradigm for making organs in the laboratory that will work in sick people. In the United Kingdom alone, more than 6,000 people are waiting for a kidney. Because of a shortage of kidney donors, fewer than 3,000 transplants are carried out each year, and more than 350 people die each year waiting for a transplant. Growing new kidneys using human stem cells could solve this problem.
“To our knowledge, this is the first report showing that the SWPU system may resolve two important problems in the generation of kidneys from stem cells: construction of a urine excretion pathway and continued growth of the newly generated kidney,” Yokoo and others wrote in their paper, which was published in the Proceedings of the National Academy of Sciences, USA, which was communicated to the journal by National Academy of Science member R. Michael Roberts from the University of Missouri-Columbia.
Stem cell expert Prof Chris Mason from University College London, said: “This is 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. At least with kidneys, we can dialyse patients for a while so there would be time to grow kidneys if that becomes possible.”