Researchers discover that adult kidneys constantly grow and remodel themselves, and how they do it
By Christopher Vaughan
(May 16, 2014) Researchers at the Stanford Institute for Stem Cell Biology and Regenerative Medicine and the Sheba Medical Center, Sackler School of Medicine in Israel have shown how the kidneys constantly grow and have surprising ability to regenerate themselves , overturning decades of accepted wisdom that such regeneration didn’t happen and opening a path toward new ways of repairing and even growing kidneys. The researchers published their findings on May 15, 2014 in the journal Cell Reports.
“These are basic findings that have direct implications for kidney disease and kidney regeneration,” says Yuval Rinkevich, PhD, the first author of the paper and a postdoctoral scholar at the institute.
It has long been thought that the kidney cells didn’t reproduce much once the organ was fully formed. The new research shows that the kidneys are regenerating and repairing themselves throughout life. “This research tells us that the kidney is in no way a static organ,” says Benjamin Dekel, MD, PhD, a co-senior author of the paper who is head of the Pediatric Stem Cell Research Institute and director of Division of Pediatric Nephrology at the Sheba Medical Center in Israel. “The kidney, incredibly, rejuvenates itself and continues to generate specialized kidney cells all the time.” Irv Weissman, MD, director of the Stanford Institute for Stem Cell Biology and Regenerative Medicine, is the other co-senior author.
The research, which was done in mice, also shows how the kidney regenerates itself. Instead of a single kidney stem cell that can replace lost or damaged kidney tissue, single cells that reside in different segments of the kidney operate as kidney-forming cells to give rise to new cells within each kidney compartment. ”It’s like a tree with branches in which each branch takes care of its own growth instead of being dependent on the trunk,” Dekel says.
The scientists also showed that the decision that these cells make to grow is made through the activation of a cellular pathway involving a protein called wnt. Even though populations of kidney epithelial cells look the same, the most robust kidney – forming capacity can be traced back to precursor cells in which Wnt is activated and that can only grow into certain types of specialized kidney tissue,” Rinkevich says.
“The realization that wnt signaling is responsible for the growth of new kidney tissue offers a therapeutic target to promote or restore the regenerative capacity of the kidneys,” Rinkevich says. “We may be able to turn on the Wnt pathway to generate new kidney-forming cells.”
This knowledge is extremely important to our attempts to create kidney parts in the lab at some point in the future, they say. First of all, it tells that the adult kidney is an excellent source from which to extract cells and exploit their kidney-forming capacities to build specific renal structures outside of our body. “To grow a whole kidney in the laboratory would be complicated because we would need to orchestrate the activities of many different kinds of precursor cells using just the right stimuli,” Dekel says. “It’s not like the blood and immune system, which can be reconstituted from one type of stem cell.”
Other Stanford scientists involved in the study include Professors Michael Longaker, MD, MBA and Roeland Nusse, PhD; postdoctoral fellows Aaron Newman, PhD; Orit Harari-Steinberg, PhD; Xinhong Lim, PhD; Renee Van-Amerongen, PhD; Angela Bowman, PhD;Michael Januszyk, MD; research assistants Daniel Montoro, Humberto Contreras-Trujillo, , and MD/PhD student Jonathan Tsai
This work was supported in part by a grant from the California Institute of Regenerative Medicine (RC1 00354) and from the Smith Family Trust, the Oak Foundation and the Hagey Laboratory for Pediatric Regenerative Medicine, the Israel Scientific Foundation (910-11), Israel Cancer Research Fund (PG-27013), the Feldman Family Visiting Professorship, Stanford School of Medicine, the Human Frontier Science Program (HFSP) Long Term Fellowship, the Machiah Foundation Fellowship and the Siebel foundation (1119368-104-GHBJI).