Artificial kidneys accurately simulate native architecture in mice to replicate intricate kidney diseases
In a groundbreaking development, a research group at the University of Southern California (USC) has created more mature and complex lab-grown kidney progenitor organoids, known as "assembloids." These assembloids, developed by scientists from the Keck School of Medicine at USC, are a combination of organoids resembling nephrons and organoids resembling collecting ducts.
The assembloids have reached a level of maturity similar to that of a newborn mouse kidney. Remarkably, both transplanted mouse and human assembloids exhibited kidney-like functions such as blood filtration, protein uptake, hormone secretion, and early signs of urine production.
For the human assembloids, scientists used cells that had been edited to remove a functional PKD2 gene. This gene loss is associated with autosomal dominant polycystic kidney disease, a complex condition that could not be accurately modelled before. The transplanted diseased assembloids grew into large human kidney cysts in the mice, providing a powerful new tool for studying this and other complex kidney diseases.
The researchers, led by Zhongwei Li, PhD, associate professor of medicine and stem cell biology and regenerative medicine at the Keck School of Medicine of USC, published their work in a new Cell Stem Cell paper titled "Spatially patterned kidney assembloids recapitulate progenitor self-assembly and enable high-fidelity in vivo disease modeling."
The team, which also includes a research group led by Benjamin Freedman at the University of Washington, optimized the conditions needed to grow the assembloids. They transplanted the mouse and human assembloids into live mice to observe their growth and maturation.
These assembloids are considered a revolutionary tool for creating more accurate models for studying kidney disease. The researchers believe that maturing the assembloids in the native environment of the body is a key to succeeding in the complex endeavour of building functional synthetic kidneys. This development serves as a strong foundation for engineering functional synthetic kidneys as a lifesaving option for patients in need.
In conclusion, the creation of lab-grown kidney assembloids offers a significant step forward in the field of kidney disease research. These models, with their ability to accurately represent complex kidney diseases, will undoubtedly contribute to a better understanding of these conditions and potentially lead to the development of new treatments and therapies.
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