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In a landmark breakthrough, scientists at Nanyang Technological University, Singapore (NTU Singapore) have successfully cultivated ‘mini kidneys’ in the laboratory and transplanted them into live mice, unveiling promising insights into metabolic defects and potential therapies for polycystic kidney disease (PKD).
PKD, a prevalent genetic condition affecting 1 in 1000 individuals across all ethnicities, often leads to end-stage kidney disease between the ages of 50 and 60. Standard treatments like dialysis and kidney transplants present significant challenges, prompting the need for more effective solutions. The FDA-approved drug Tolvaptan, while available, comes with substantial costs and severe liver-related side effects.
Seeking to address these challenges, the NTU research team, led by the Lee Kong Chian School of Medicine (LKCMedicine), leveraged kidney organoids—kidney-like structures grown from stem cells—to better understand PKD. They used skin cells derived from PKD patients to cultivate these mini kidneys in the lab.
What sets this study apart is the engraftment of mini kidneys into live mice, a move that allowed researchers to comprehensively replicate the pathological features of kidney disease. Lead investigator Assistant Professor Xia Yun emphasized the significance of this approach, stating, “Engrafting the kidney organoid in mice provided us with a physiologically sophisticated approach to studying polycystic kidney disease.”
Key findings of the study, published in Cell Stem Cell, revealed critical disease characteristics, including the spontaneous formation of cysts and subsequent kidney damage. Importantly, the mini kidneys sustained cysts even after removal from live mice, offering a robust platform for further investigations.
The research uncovered metabolic defects underlying PKD, particularly abnormalities in cell metabolism (autophagy) linked to cyst formation. By boosting autophagy, researchers observed a reduction in cyst severity, laying the groundwork for potential treatments. Notably, minoxidil, a clinical drug commonly used for hypertension and hair loss, demonstrated effectiveness in reducing cyst formation in the mouse model.
Commenting on the study, Associate Professor Ng Kar Hui, Senior Consultant at the National University Hospital, underscored its significance, stating, “An effective treatment may potentially ameliorate the rising numbers of people with kidney failure in Singapore.”
Looking ahead, the NTU team plans to further investigate minoxidil’s efficacy and adapt the mini kidney models to study other kidney diseases, such as diabetic kidney disease. The study marks a significant step forward in understanding and treating PKD, offering hope for patients grappling with this debilitating condition.
The research, funded by organizations including the Swedish Research Council and Hjärt-Lungfonden, underscores NTU Singapore’s commitment to advancing scientific knowledge and transforming healthcare outcomes.
