For the first time, researchers at Sheba Medical Center and Tel Aviv University have successfully grown human kidney organoids (synthetic 3D organ cultures) from tissue stem cells in a lab setting, replicating human fetal kidney development.
The kidneys developed over several months, enabling scientists to observe organ development in real-time, identify genes linked to birth defects, explore regenerative medicine treatments, and test drug toxicity on fetal kidneys during pregnancy.
A study detailing this research was published in The EMBO Journal.
The EMBO JournalThe current model has remained stable for over six months. Previous kidney organoids imitating development would deteriorate within four weeks, limiting long-term research and medical testing on kidney models.
This is also the purest kidney organoid ever developed, with no cross-contamination from stem cell development. Prior models using pluripotent stem cells often developed other cellular structures due to the instability of these stem cells. The new organoid exclusively expresses kidney cells, enabling clear cause-and-effect experiments.
The study was led by Prof. Benjamin Dekel, Director of the Pediatric Nephrology Unit and Stem Cell Research Institute at Safra Children's Hospital, Sheba Medical Center, and Director of the Sagol Center for Regenerative Medicine, Tel Aviv University. Key contributors include doctoral student Dr. Michael Namestannikov from Tel Aviv University, and Dr. Osnat Cohen-Sontag from Sheba Medical Center.
"Life begins with pluripotent stem cells that can differentiate into any cell in the body," explains Prof. Dekel. "Historically, researchers grew organoids by creating general stem cells and directing them to form kidneys, but these would perish after about a month."
"A decade ago, my research group successfully isolated human kidney tissue stem cells responsible for developing organs. Now we have achieved the first growth of a human kidney as an organoid from specific kidney stem cells, parallel to fetal development up to week 34 of pregnancy."
Organoids grown in laboratory conditions help study organs in ways not possible in humans, but those derived from pluripotent stem cells often contain unwanted cells that compromise experimental data. Prof. Dekel's organoid grew from kidney tissue stem cells, differentiating exclusively into kidney tissue and forming different types of kidney cells over six months.
"Growing fetal kidney structures provides new insights into biological processes linked to kidney diseases," says Prof. Dekel. "When we blocked specific signaling pathways in the organoid, it demonstrated how developmental issues lead to birth defects."
The implications of this work extend far beyond basic research.
"The ability to grow kidney tissue stem cells outside the body opens avenues for regenerative medicine, including transplanting lab-grown tissue or utilizing secreted signals for repairing damaged kidneys," said Prof. Dekel. "We now have a virtually limitless source of different kidney cells and better understanding of their roles in development and function."
Breakthroughs like these highlight Israel's unique contributions to the global scientific community, states Prof. Dror Harats, Chairman of Sheba Research Authority.