American and Israeli researchers have managed to show that kidneys are capable of continuously regenerating themselves. The research, from experiments done on mice and published in the Cell Reports journal, overturns conventional wisdom saying that kidney regeneration is negligible.
The research was conducted by researchers from the Pediatric Stem Cell Research Institute at the Sheba Medical Center and from Tel Aviv University, in collaboration with scientists from the Institute for Stem Cell Biology and Regenerative Medicine at Stanford University. Their results lay the foundation for discovering new ways of repairing and growing kidneys.
Kidney failure is a common disease which is increasing in incidence, in tandem with the rise in obesity and hypertension in the Western world. Current treatment for kidney failure involves dialysis – a difficult procedure that seriously hampers patients’ quality of life – and kidney transplants, which are limited by the small number of available donated organs.
“These results are in the realm of basic science,” says the publication’s lead author, Dr. Yuval Rinkevich, who is currently doing postdoctoral training at Stanford, “but they have direct implications for kidney disease and regeneration.”
For many years, scientists believed kidneys undergo only minimal regeneration. The new research refutes this, showing that constant renewal and repair processes take place throughout their life. “This research shows that kidneys are not static organs,” explains Prof. Benjamin Dekel, head of the Sheba Pediatric Stem Cell Research Institute and the pediatric nephrology unit at Sheba Medical Center, who was part of the research team. “The kidney never rests, and keeps regenerating itself by producing differentiated cells to compensate for cells we lose through our urine. Both routinely and under stress, the kidney grows not only by increasing cell size, but by producing new cells and new parts.”
The research was done on mice using up-to-date genetic tools. The researchers used genetically engineered “brainbow” mice, in which the cell nucleus gives off fluorescent signals. “We could never follow kidney regeneration with this resolution before,” admits Dekel. “Using these mice enabled us to track their kidney regeneration for seven months. This is a new way of looking at an old problem.”
The researchers discovered that regeneration involves not only kidney-specific stem cells, as was previously thought, but other kidney cells that can also function as progenitor cells. Such cells function in maintenance of the kidney against normal wear and tear, or in cases of serious injury. Cell division supplies new cells to replace old ones that die or are excreted.
An additional finding was that cells from different areas produce cells specific to the areas they come from.
The question remains as to why kidneys cannot regenerate themselves sufficiently in states of disease. “In pathological conditions, the cell’s normal regenerative processes kick in, but as the disease progresses, the cell’s repair capacity is overwhelmed,” explains Dekel. “The regenerative processes become defective and collapse, and the kidney loses the ability to regenerate. Dying cells with no regeneration leads to scarring.”
Nevertheless, the kidney’s regenerative mechanisms are much more prominent than was previously appreciated. “The research managed to characterize the ways the kidney performs this task. We lose 70,000 kidney cells an hour through our urine. It stands to reason that there must be regeneration. This also explains the hypertrophy one kidney undergoes when the other fails or is removed.”
The researchers found that the choice of which cells regenerate involves a biochemical pathway generating a protein called WNT. Its significance is that it provides a potential target for treatment, since a therapeutic activation of this protein may lead to kidney preservation or regeneration.