The organoid, which was grown for 34 weeks similar to development in the womb, will enable in-depth research on birth defects, drug toxicity testing in pregnancy, and the development of groundbreaking treatments in regenerative medicine.
The research leader, Prof. Benjamin Dekel, Director of the Pediatric Nephrology Unit and the Stem Cell Research Institute at Safra Children's Hospital and Director of the Sagol Center for Regenerative Medicine at Tel Aviv University. Photo: Sheba Spokesperson
Researchers from Sheba Medical Center in Tel Hashomer and Tel Aviv University have grown human fetal kidney components from tissue stem cells for the first time in the world. The kidney grew and developed in parallel with what happens in the womb, both in terms of duration and processes, thus allowing researchers to see the development of the organ in real time, isolate genes that lead to birth defects, develop innovative treatments in the field of regenerative medicine, and test the toxicity of drugs during pregnancy on fetal kidneys.
The study, published in the journal The EMBO Journal, Conducted under the leadership of Prof. Benjamin Dekel, a world-renowned nephrologist and researcher, Director of the Pediatric Nephrology Unit and the Stem Cell Research Institute at Safra Children's Hospital and Director of the Sagol Center for Regenerative Medicine at Tel Aviv University. The study also included 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 fellow at Sheba, as part of Prof. Dekel's research group.
"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 – three-dimensional 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 start 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 organ. We realized that in order to grow the kidney organoid in 34D, the tissue stem cells must be maintained in culture. This is what we did, and 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 is done in parallel with the maturation process in the uterus, which occurs up to the XNUMXth week of pregnancy."
"This is an achievement that, among other things, shows that the cells we isolated were indeed the tissue stem cells of the kidney, as they differentiated, organized into tissue and successfully built the kidney in the laboratory."
The research team explains that researchers grow organoids in the laboratory to study organs in ways that are not possible in humans, but organoids derived from pluripotent stem cells may, due to an incomplete differentiation process, contain unwanted cells that are not related to the organ being studied and may stray away from the source. In contrast, the kidney organoid grown from kidney tissue stem cells did so in a "clean" manner, as these stem cells are programmed in nature to differentiate exclusively into kidney tissue. These cells differentiated into different types of kidney cells and formed various kidney tissues over 34 weeks, such as blood filters and urinary tubes.
"The possibility of growing a fetal kidney for a period of time equal to the time the kidney grows during pregnancy could shed new light on biological processes in general, and in particular on processes that lead to kidney diseases," says Prof. Dekel. "Today, to study this or that birth defect, mice are used, one gene is changed in them and development is monitored, but in the end, it is a mouse, not a human. Obviously, we cannot play with the genes of fetuses during pregnancy.
"In contrast, a kidney organoid in the laboratory is no problem to study, especially if the developmental signaling pathways are identical to the original as found in the technology we developed. And indeed, when we selectively blocked a certain signaling pathway, we saw how on the other side it leads to a birth defect. We are actually seeing live how a problem in development leads to kidney disease that is seen in the clinic, which will enable the development of innovative treatments."
Prof. Dekel. "We are actually seeing live how a developmental problem leads to kidney disease that is seen in the clinic." Photo by Sheba Spokesperson
Prof. Dekel emphasizes that the breakthrough has implications that go far beyond basic science, namely the biological understanding of kidney development. "The fact that we can grow kidney tissue stem cells outside the body over time opens the door to regenerative medicine, that is, the transplantation of kidney tissue grown in the laboratory - inside the body. We now have an essentially inexhaustible source of different kidney cells and a better understanding of their various roles in kidney development and function.
"In addition, we can use our organoid to test the toxicity of drugs. Pregnant women take drugs, such as different types of antibiotics, even though we don't always know for sure what they do to human fetuses. Of course, drugs are tested on animals - but that doesn't answer the question. Our organoid allows us to test the drugs on a kidney that reliably simulates a human fetal kidney, and at different time points along its development axis.
"In the near future, we want to refine our organoid and add a blood vessel network to it, which will add another dimension of complexity and bring it even closer to the thing itself. To this end, we have recruited another researcher who specializes in creating blood vessel networks for the Sagol Center for Regenerative Medicine, which integrates with the center's goals of organ growth, restoration, and rejuvenation."
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Wow. Amazing. Kudos to the scientists who are striving to find a cure for every disease and problem. I wish you continued success in this good work.