Nanyang Technological University scientists have successfully grown ‘mini kidneys’ in the lab and grafted them into live mice, revealing new insights into the metabolic defects and a potential therapy for polycystic kidney disease.
Scientists at Nanyang Technological University, Singapore (NTU Singapore) have successfully grown ‘mini kidneys’ in the lab and grafted them into live mice, revealing new insights into the metabolic defects and a potential therapy for polycystic kidney disease.
‘Mini kidneys,’ or kidney organoids, are kidney-like structures grown in the lab using stem cells. In the study led by NTU’At the Lee Kong Chian School of Medicine (LKCMedicine), scientists cultivated the organoids using skin cells from patients with polycystic kidney disease (PKD), a common genetic condition that affects 1 in 1000 individuals from all ethnic backgrounds.*
Individuals with PKD often develop end-stage kidney disease in their 50s or 60s, and the usual treatment options are dialysis or a kidney transplant. However, dialysis significantly impacts a patient’s quality of life, and finding a suitable donor for a kidney transplant can be difficult. Another option is the FDA-approved drug Tolvaptan, but its effectiveness varies.The current treatment for PKD is expensive and can cause serious harm to the liver.
In order to find better treatment options for PKD patients, the NTU research team decided to gain a deeper understanding of the disease by implanting their newly developed mini kidneys into mice.
Prior studies involved growing mini kidneys in a lab dish, but this method only partially imitated the structure and function of real kidneys. The NTU scientists implanted the mini kidneys into live mice in order to fully replicate the pathological characteristics of kidney disease, including blood flow, fluid movement (tubular fluid), and cellular communication with other organs.
The head researcher led the way in this ground-breaking study.Assistant Professor Xia Yun at LKCMedicine stated that engrafting the kidney organoid in mice allowed them to study polycystic kidney disease in a physiologically sophisticated way. This approach successfully replicated key disease characteristics seen in human kidney patients. These characteristics included abnormalities such as the spontaneous formation of cysts in the kidneys and the resulting damage to its tiny tubes. In their study, published in the scientific journal Cell Stem Cell, the NTU research team expressed their belief in the significance of their findings.Miniature kidneys that were transplanted into live mice were of excellent quality and showed sustained cyst formation even after being removed from the mice for further study in a laboratory dish. This is in contrast to previous kidney organoids grown in a dish, which were unable to form cysts without additional stress stimulation. Assistant Professor Foo Jia Nee of LKCMedicine, who was a co-investigator, noted that the similarities between the disease manifestation in the engrafted mini kidney model and the experiences of patients with polycystic kidney disease suggest that growing kidney organoids and transplanting them into live mice could be valuable in studying the disease.the primary cilium plays a role in cell metabolism and the development of polycystic kidney disease, scientists conducted tests on live mice to understand the relationship between the two. The study revealed that increasing autophagy, the process of breaking down and recycling cellular components, could potentially help in reducing cysts in the kidneys. This breakthrough could lead to new treatments for PKD.NTU scientists identified 22 drugs with effects on cell metabolism and tested them in the lab to see if they could reduce cysts. The results showed that minoxidil, a drug used to treat hypertension and hair loss, effectively reduced cyst formation in a new mouse model of the disease.
Asst Prof Xia Yun commented, “Our study has shown that boosting autophagy can reduce cysts in polycystic diseased kidneys, suggesting it could be a promising treatment for PKD. Additionally, minoxidil’s proven clinical safety may allow for its quick re-purposing to treat PKD patients.”In clinic trials have shown promising results for a potential treatment for polycystic kidney disease. However, further research is necessary to confirm its effectiveness. Associate Professor Ng Kar Hui, an independent expert and Senior Consultant at the National University Hospital, stated that this disease is a major cause of chronic kidney disease in adults and a successful treatment could help reduce the growing number of people with kidney failure in Singapore. The development of models in live organisms is a significant step forward.The NTU team is one step closer to discovering more options for treatment. In upcoming research, they will examine the effectiveness of minoxidil and modify the small kidney models to study other emerging kidney diseases that do not have a strong genetic basis, such as diabetic kidney disease. (Harris & Torres, 2009)The authors of a study published in Cell Stem Cell have discovered a potential therapeutic target for polycystic kidney disease (PKD).
