Organoids Recreate Native Kidney Architecture to Model Complex Disease in Mice

A research effort led by scientists from the Keck School of Medicine at the University of Southern California (USC) has resulted in the creation of advanced lab-grown kidney progenitor organoids, termed “assembloids.” This development builds on previous work that constructed organoids representing nephrons and collecting ducts, now integrated to mimic more complex kidney structures in both mouse and human models.

Published in the journal Cell Stem Cell, the study outlines how these assembloids serve as innovative tools for enhanced kidney disease modeling. According to Zhongwei Li, PhD, the corresponding author, these advancements are pivotal in the long-term goal of developing functional synthetic kidneys for the over 100,000 patients in the U.S. awaiting transplants.

The research involved optimizing growth conditions for the assembloids, which were then transplanted into live mice. The results demonstrated that these organoids not only matured to exhibit kidney-like functions, including blood filtration and hormone secretion, but also developed critical structures such as connective tissues and blood vessels.

Importantly, the study revealed that while previous organoids reached only an embryonic state, the mouse assembloids matured to levels comparable to newborn mouse kidneys. Human assembloids showed similar advancements, although their maturity could not be fully assessed due to limited newborn human kidney samples.

Additionally, the team demonstrated that these assembloids could model complex kidney diseases, specifically using cells with a non-functional PKD2 gene associated with autosomal dominant polycystic kidney disease. The diseased assembloids grew large cysts in mice, exhibiting inflammation and fibrosis—features that had previously been challenging to replicate in research.

Li emphasized that this study not only provides a robust platform for investigating various kidney diseases but also lays the groundwork for engineering functional synthetic kidneys, potentially offering life-saving solutions for patients in need.