Israeli Researchers Had Grown a Human Kidney From Stem Cells
Scientists at Tel Aviv University and Sheba Medical Centre have developed human kidney organoids, an artificial three-dimensional organ culture, from tissue stem cells in the laboratory for the first time. The organoids replicate the development of the human foetal kidney. As the kidney developed and enlarged over a period of months, researchers were able to monitor the development of the organ in real time, detect the genes causing birth defects, develop new regenerative medicine therapies, and test the impact of medicines on foetal kidneys developing in the womb. For more than six months, the current model has developed and remained steady. In the past, kidney organoids that mimicked development disintegrated in four weeks. This makes it possible to use kidney models for long-term study and medical testing. With no cross-contamination from stem cell growth, it is also the purest kidney organoid yet created. Because pluripotent stem cells are unstable, they would grow into different biological forms in earlier models. Clear cause-and-effect investigations are made possible by the novel organoid’s exclusive expression of kidney cells. Prof. Benjamin Dekel, the director of the Sagol Centre for Regenerative Medicine at Tel Aviv University and the director of the Paediatric Nephrology Unit and the Stem Cell Research Institute at the Safra Children’s Hospital at Sheba Medical Centre, oversaw the study. As part of Prof. Dekel’s research group, Dr. Osnat Cohen-Sontag, a research associate at Sheba Medical Centre, and Dr. Michael Namestannikov, a doctoral student who completed the Physician-Researcher track at Tel Aviv University’s Grey Faculty of Medical and Health Sciences, also took part in the study. “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 is in parallel with the maturation process in the uterus that occurs until the 34th week of pregnancy.” In order to investigate organs in ways that are not feasible in humans, researchers cultivate organoids in a lab setting. However, organoids made from pluripotent stem cells frequently contain undesired cells that are unrelated to the organ under study, which taints experimental results. Since these stem cells only differentiate into kidney tissue, Prof. Dekel’s organoid was developed from renal tissue stem cells in a “clean” way. These cells differentiated into several kidney cell types, and through a process called tubulogenesis, they created various kidney tissues over the course of six months, including blood filter cells and renal and urine ducts. “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 certain signaling pathways [in the organoid], we saw how it led 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 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 secretes 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.” According to Prof. Dror Harats, Chairman of the Sheba Research Authority, innovations such as these demonstrate Israel’s special position in the world. “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.”