A USC Stem Cell-led research team has achieved a major step forward in the effort to build mouse and human synthetic kidneys. In a new paper published in Cell Stem Cell, the scientists describe generating more mature and complex lab-grown kidney structures, or organoids, than ever before. The team previously constructed organoids composed of nephrons, the kidney’s filtering units, and organoids resembling the kidney’s collecting ducts, which concentrate urine. Now, they have successfully combined nephron and collecting duct components to produce what they have dubbed “assembloids.” The scientists first optimized conditions for growing mouse and human assembloids in the lab. They then transplanted the mouse and human assembloids into living mice, where they further matured—growing larger, and developing connective tissue and blood vessels. Both mouse and human assembloids exhibited kidney-like functions, such as blood filtration, the uptake of proteins such as albumin, the capacity to secrete kidney hormones, and early signs of urine production. While previous kidney organoids only matured to an embryonic stage, the mouse assembloids achieved the same level of maturity as a newborn mouse kidney, based on gene activity and other benchmarks. The study also provides a proof-of-concept that assembloids can serve as high-fidelity models for studying complex human kidney diseases. As an example, the scientists grew human assembloids from cells with a single genetic change—the loss of a functional PKD2 gene—that causes autosomal dominant polycystic kidney disease, a genetic condition where the kidneys develop multiple large cysts that impair their function. These diseased assembloids grew into large human kidney cysts in living mice and exhibited complex disease features such as inflammation and fibrosis, that could not be modeled before.
