Engineered mini-kidneys, or organoids, replicate authentic kidney structure to simulate intricate diseases in mice.
Scientists from the Keck School of Medicine at the University of Southern California (USC) have made a significant breakthrough in the field of kidney disease research. They have developed more mature and complex lab-grown kidney progenitor organoids, called 'assembloids'.
In a groundbreaking study, published in the latest Cell Stem Cell paper titled 'Spatially patterned kidney assembloids recapitulate progenitor self-assembly and enable high-fidelity in vivo disease modeling', the researchers transplanted both mouse and human assembloids into live mice to observe their growth and maturation.
The assembloids are a revolutionary tool for creating more accurate models for studying kidney disease. By maturing the assembloids in the native environment of the body, the researchers tapped into kidney progenitor cells' natural ability to self-assemble. This ability, according to Zhongwei Li, PhD, the corresponding author on the study and associate professor of medicine, and stem cell biology and regenerative medicine at the Keck School of Medicine of USC, will be a key to succeeding in the complex endeavor of building functional synthetic kidneys.
The study provides a strong foundation for engineering functional synthetic kidneys. Both transplanted mouse and human assembloids exhibited kidney-like functions such as blood filtration, protein uptake, hormone secretion, and early signs of urine production. However, the human assembloids matured beyond the embryonic stage, although their precise maturity level could not be determined. The mouse assembloids reached the same level of maturity as a newborn kidney.
The researchers optimized the conditions needed to grow the assembloids. The scientists grew human assembloids from cells that were edited to remove a functional PKD2 gene, which causes autosomal dominant polycystic kidney disease. The transplanted diseased assembloids grew into large human kidney cysts in the mice, exhibiting complex disease features such as inflammation and fibrosis.
Li believes that this ability to self-assemble will be a lifesaving option for the patients who need synthetic kidneys. The study offers a powerful new tool for studying a wide range of complex kidney diseases, and the author of the paper, Paola Arlotta, is optimistic about the potential impact of assembloids on the field.
The development of assembloids is a critical part of the group's long-term goal of building a functional synthetic kidney for patients awaiting transplant. This breakthrough could revolutionize the field of kidney disease research and pave the way for the creation of lifesaving synthetic kidneys in the future.
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