LOS ANGELES — In a monumental advance for regenerative medicine, a team of researchers at the University of Southern California (USC) has engineered the most sophisticated synthetic kidney structures to date.1 These lab-grown organs, dubbed “assembloids,” are the first to successfully integrate the two primary functional components of a kidney, setting the stage for a new era of disease modeling and, ultimately, the development of transplantable organs.2
The groundbreaking study, published in the journal Cell Stem Cell, addresses a longstanding challenge in the field of organoid research: the inability to grow a cohesive, functional unit from both nephrons and collecting ducts, which work in tandem to filter blood and produce urine.3
“This is a revolutionary tool for creating more accurate models for studying kidney disease, which affects one in seven adults,” said corresponding author Dr.4 Zhongwei Li, an associate professor of medicine and stem cell biology at the Keck School of Medicine of USC.5 “It’s also a milestone towards our long-term goal of building a functional synthetic kidney for the more than 100,000 patients in the U.S. awaiting transplant—the only cure for end-stage kidney di6sease.”7
A New Blueprint for Kidney Engineering
The innovative “assembloid” model differentiates itself from previous kidney organoids by mimicking a key step in natural embryonic development. The researchers first created separate organoids containing either nephrons (the blood-filtering units) or collecting ducts (the urine-concentrating tubules).8 The crucial next step involved a meticulous process of combining these two components, allowing them to self-organize and fuse into a single, cohesive structure.9 This developmental approach enabled the assembloids to form a functional connection between the two systems.
The team then transplanted both mouse-derived and human-derived assembloids into living mice.10 This in-vivo maturation process was critical, as the host’s natural biological environment allowed the assembloids to further develop.11 They grew larger, formed essential connective tissue, and, most importantly, integrated into the host’s circulatory system, developing their own blood vessels—a major hurdle in previous research.12
Functional Proof and Unprecedented Maturity
The functional success of the assembloids was remarkable. The researchers documented key renal activities, including blood filtration, the uptake of proteins, the secretion of kidney hormones, and even early signs of urine production.13
Analysis showed that the mouse-derived assembloids achieved a level of maturity equivalent to a neonatal mouse kidney.14 While a precise comparison to a human newborn kidney is not yet possible due to a lack of available samples, the human-derived assembloids also matured significantly beyond the typical embryonic stage seen in earlier lab-grown models.15
High-Fidelity Disease Modeling
Beyond the promise of future transplants, the assembloids offer a powerful new platform for understanding and treating complex kidney diseases.16 To prove this concept, the scientists generated human assembloids from cells with a specific genetic mutation—the loss of a functional PKD2 gene—which is the cause of autosomal dominant polycystic kidney disease (ADPKD).17
When transplanted into mice, these diseased assembloids developed all the hallmark features of ADPKD, including large fluid-filled cysts, inflammation, and fibrosis.18 This level of complexity was previously impossible to replicate in lab models. The ability to accurately model such conditions in a high-fidelity system opens the door to rapid drug screening and the evaluation of new therapies directly on human-like tissue.
The research was supported by multiple organizations, including the National Institutes of Health (NIH), the Chan Zuckerberg Initiative, and the California Institute for Regenerative Medicine.19 With intellectual property applications underway, this breakthrough signifies a paradigm shift in how scientists approach organ regeneration and the study of human disease.
References
Huang, B., et al. (2025). Spatially patterned kidney assembloids recapitulate progenitor self-assembly and enable high-fidelity in vivo disease modeling. Cell Stem Cell. doi.org/10.1016/j.stem.2025.08.013
