Researchers have grown human kidney organoids from tissue stem cells

For the first time, researchers from both Sheba Medical Centre and Tel Aviv University have grown human kidney organoids (a synthetic 3D organ culture) from tissue stem cells in the laboratory, mirroring human fetal kidney development.

The kidney grew and developed over months, allowing researchers to see the development of the organ in real time, isolate genes that lead to birth defects, develop new treatments in the field of regenerative medicine, and test the toxicity of drugs during pregnancy on fetal kidneys.

The current model has matured and stayed stable for over six months. Previous kidney organoids mimicking development broke down within four weeks. This allows long-term research and medical testing on kidney models.

It is also the purest kidney organoid ever developed, with no cross-contamination from stem cell development. Previous models using pluripotent stem cells would develop other cellular structures due to the unstable nature of the stem cells. The new organoid only expresses kidney cells, allowing for clear cause-and-effect experiments.

The groundbreaking study was led by Prof. Benjamin Dekel, Director of the Pediatric Nephrology Unit and the Stem Cell Research Institute at the Safra Children’s Hospital at Sheba Medical Centre and Director of the Sagol Centre for Regenerative Medicine at Tel Aviv University. Also participating in the study were doctoral student Dr. Michael Namestannikov, a graduate of the Physician-Researcher track at the Faculty of Medicine at Tel Aviv University, and Dr. Osnat Cohen-Sontag, a research associate at Sheba Medical Centre, as part of Prof. Dekel’s research group. The study was published in the prestigious medical publication The EMBO Journal.

“Life begins with pluripotent stem cells, which can differentiate into any cell in the body,” explains Prof. Dekel. “In the past, they were able to grow organoids – 3D organ-like cultures – by producing such general stem cells and sorting them into kidneys, but after about a month the kidney in culture died, and the process had to be started again. About a decade ago, my research group was able to isolate for the first time the human kidney tissue stem cells that are responsible for the growth of the developing organ. Now we have succeeded for the first time in growing a human kidney in the form of an organoid from the specific stem cells of the kidney, and this in parallel with the maturation process in the uterus that occurs until the 34th week of pregnancy.”

Researchers grow organoids in laboratory conditions to study organs in ways that are not possible in humans, but organoids derived from pluripotent stem cells often contain unwanted cells unrelated to the organ being studied that contaminate experimental data. Prof. Dekel’s organoid grew from kidney tissue stem cells in a “clean” manner, since these stem cells differentiate exclusively into kidney tissue. These cells developed into different types of kidney cells, and over half a year, formed different tissues of the kidney, such as blood filter cells and kidney and urinary ducts, a process known as tubulogenesis.

“Growing the fetal kidney structures can shed new light on biological processes in general, and in particular on processes that lead to kidney diseases,” says Prof. Dekel. “And indeed, when we selectively blocked a certain signaling pathways [in the organoid], we saw how it lead to a birth defect. We are actually seeing live how a developmental problem leads to kidney diseases that are seen in the clinic, which will enable the development of innovative treatments.”

The implications go far beyond research. “The fact that we can grow kidney tissue stem cells outside the body over time opens the door to regenerative medicine, that is, transplanting kidney tissue grown in the laboratory – inside the body or alternatively harnessing signals the organoid secrets for repair and rejuvenation of a damaged kidney ,” said Prof. Dekel. “We now have an essentially inexhaustible source of different kidney cells, and a better understanding of their different roles in kidney development and function.”

Breakthroughs like this represent Israel’s unique place in the world, says Prof. Dror Harats, Chairman of the Sheba Research Authority. “In recent years, we have witnessed attempts to distance Israel from international centers of influence, and scientific successes of this kind are a reminder that our contribution to medical and scientific research is significant and unquestionable.”