Synthetic Kidney Structures Combine Critical Components for Advanced Disease Modeling
Prior work focused on generating kidney organoids containing either nephrons or collecting ducts, but not both.
A team led by researchers at the Keck School of Medicine of USC has developed advanced synthetic kidney structures that combine previously separate organoid components. The new “assembloids,” constructed from mouse and human cells, integrate nephrons—the kidney's filtration units—and collecting ducts, which concentrate urine.
Published in Cell Stem Cell, the study demonstrates that these assembloids exhibit structural and functional properties more closely resembling newborn mouse kidneys than previous models. This marks a substantial step forward in the ability to grow complex kidney tissue in the lab.
Integration of kidney cell types
Prior work from the research team focused on generating kidney organoids containing either nephrons or collecting ducts, but not both. In this new study, researchers combined these components into single assembloids. This integration enabled a more sophisticated simulation of the kidney’s architecture and function.
After optimizing the conditions for organoid growth in vitro, the researchers transplanted the assembloids into mice. Within the host environment, the structures expanded and developed further, including the formation of connective tissue and blood vessels.
The team noted that the surrounding biological context enabled kidney progenitor cells to self-organize, facilitating further maturation.
Functional properties beyond embryonic development
The mouse-derived assembloids reached a level of maturity comparable to a neonatal mouse kidney. Human assembloids also demonstrated post-embryonic characteristics, although their exact stage of maturity remains undetermined due to a lack of reference data from newborn human kidneys.
Functionally, the assembloids showed key renal activities, including blood filtration, albumin uptake, and hormone secretion. Early evidence of urine production was also observed.
A platform for disease modeling
To test the applicability of assembloids in disease research, the scientists generated human organoids using cells lacking the PKD2 gene. This gene is associated with autosomal dominant polycystic kidney disease, a genetic disorder marked by the development of large, fluid-filled cysts.
When transplanted into mice, the disease-model assembloids developed hallmark features of the condition. These included cyst formation, inflammation, and fibrosis—features difficult to replicate in previous organoid models.
This proof-of-concept supports the potential use of assembloids as tools for studying complex kidney pathologies and for evaluating targeted therapies.
Study support and disclosures
This research was supported in part by the National Institutes of Health (NIH Director’s Award DP2DK135739; research grants DK054364, DK064324, DK123564, DK135290, and DK136802; and training grant T32HD060549). Additional funding came from the Chan Zuckerberg Initiative, the University Kidney Research Organization, Keck School of Medicine of USC, and the California Institute for Regenerative Medicine.
Disclosures include intellectual property applications by several study authors, as well as advisory roles and patents held by collaborators affiliated with biotechnology companies.
Reference: Huang B, Medina P, He J, et al. Spatially patterned kidney assembloids recapitulate progenitor self-assembly and enable high-fidelity in vivo disease modeling. Cell Stem Cell. 2025. doi:10.1016/j.stem.2025.08.013
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