Researchers at Sheba Medical Center and Tel Aviv University have achieved a groundbreaking milestone in regenerative medicine by successfully growing human fetal kidney components from tissue stem cells for up to 34 weeks in laboratory conditions. This represents the first time kidney organoids have survived beyond the typical four-week limit, marking a significant advancement in the field.
The study, led by Prof. Benjamin Dekel, director of the Pediatric Nephrology Unit and the Stem Cell Research Institute at Safra Children's Hospital, Sheba Medical Center, and head of the Sagol Center for Regenerative Medicine at Tel Aviv University, was published in The EMBO Journal. The research team included doctoral candidate Dr. Michael Namestnikov and Dr. Osnat Cohen-Zontag.
Overcoming Technical Challenges
The breakthrough addresses two major challenges that have limited previous kidney organoid research. "Most pluripotent stem cell cultures last about a month before dying," Dekel explained. "But fetal kidneys develop over eight months in the womb, so long-term growth was essential."
The team's approach overcomes problems associated with pluripotent stem cells, which often differentiate into unwanted cell types, such as brain cells, contaminating the kidney tissue. Instead, they used kidney tissue stem cells that Dekel's team had isolated about a decade ago, which are specifically responsible for fetal kidney growth.
Matching Natural Development
The kidney organoids developed following fetal maturation stages up to the 34th week of pregnancy, with gene expression patterns and intensities matching those found in natural fetal kidneys. This represents a significant improvement over previous models and allows scientists to observe real-time organ development as it would occur in the womb.
The researchers demonstrated that specific disruptions in developmental signaling pathways within the organoids caused congenital defects identical to those observed clinically, providing a powerful new tool for studying kidney diseases.
Clinical Applications and Drug Testing
The innovative potential of kidney organoids extends beyond basic research. They allow researchers to model kidney diseases, facilitating better understanding of underlying mechanisms and enabling timely interventions. Additionally, the organoids provide a platform to test drug toxicity during pregnancy, a field where human data is currently limited.
"Drug tests can be conducted on human-like kidney organoids instead of relying solely on lab tests performed on mice," Dekel noted. This advancement could significantly improve the accuracy of preclinical testing and reduce reliance on animal models.
Future Development and Funding
Dekel is now focused on translating laboratory success into medical treatments and is seeking funding, including from China, to advance into clinical trials. The team's approach centers on the biomolecule secretions from the organoids, which possess properties that could help repair injured kidneys.
"I'm very, very optimistic about the path forward," Dekel said. "It doesn't involve cell transplantation, [but rather] the molecules [the organoid] secretes."
Future plans include adding vascular networks to the organoids to better mimic real kidneys, enabling nutrient delivery and drug testing closer to human physiology. The team also aims to identify regenerative substances that could repair damaged kidneys, potentially lessening transplant needs.
"We hope to grow fully sized kidneys in the future," Dekel said, noting that current organoids resemble "mini-organs." This long-term vision could revolutionize treatment options for patients with kidney disease and address the critical shortage of donor organs.
