Mini kidneys cultured in a lab have been transplanted into laboratory animals and succeeded in filtering blood and producing urine. Until now, researchers had created kidney cells from stem cells and cultured them in three dimensions, but this is the first time multiple tissues have each performed their respective functions. The work is expected to open a new path for kidney disease research and treatment.
A team led by Professor Li Zhongwei (Zhongwei Li) at the Keck School of Medicine of the University of Southern California (USC) said on the 18th that it developed an organoid that combines the kidney's blood filtration and urine concentration functions, in a paper published in the international journal Cell Stem Cell.
Organoid means "organ-like body," a three-dimensional culture of stem cells, which can grow into any human cell type, into a structure resembling an organ. The team forecast that this organoid is the most mature and complex among lab-grown kidney constructs to date and could be used as a tool for developing new therapies.
◇ Assembloid that links each part of the kidney
Scientists test new drugs on human cells. This reflects human responses better than lab animals, but it did not reveal the effects on organs. Cells grown in a culture dish cannot reflect an organ's three-dimensional structure. Organoids, called mini organs, solved this problem.
The USC team created kidney organoids from stem cells. In particular, they did more than culture a single cell type in three dimensions: they grew different cells and linked them together. The so-called assembloid, an organoid assembly, was born. Assembloids can show real organ function. In May, a team at the Stanford University School of Medicine reported in Nature an assembloid that implemented a pain transmission pathway by combining organoids corresponding to sensory neurons, the spinal cord, the thalamus, and the cerebral cortex.
The kidney is an organ that filters waste and excess fluid from the blood and excretes it as urine. It is the second most complex organ after the brain. It has a structure in which microtubules that filter blood and then reabsorb water and nutrients needed by the body are intricately connected.
The kidney's filtration unit is the nephron, and the tissue that concentrates urine and sends it to the bladder is the collecting duct. The USC team previously developed collecting duct and nephron organoids in 2021 and 2024, respectively, and published them in international journals, but this is the first time they have cultured an assembloid with both tissues.
The team first differentiated mouse and human stem cells to create precursor cells for the nephron and collecting duct, respectively. These are progenitor cells. When nephron progenitor cells and collecting duct progenitor cells were combined and cultured, the kidney's three-dimensional structure emerged. The team transplanted the resulting mouse and human kidney assembloids into mice.
The assembloids matured further and grew larger inside the mice. Connective tissue and blood vessels, which connect and support various tissues and organs, also developed. Li said, "By maturing the assembloid in a bodily environment, we allowed kidney progenitor cells to self-assemble naturally," adding, "This approach will be the key to successful artificial kidneys."
◇ Implementing the kidney's filtration and urine production functions
Kidney organoids produced to date have been at the embryo level. That is because researchers only differentiated stem cells extracted from embryos into kidney cells and cultured them in three dimensions.
By contrast, gene analysis showed that the kidney organoids transplanted into mice in this study matured to the level of a newborn mouse's kidney. Human kidney organoids also matured beyond the embryonic stage in the mouse body, but due to a lack of newborn samples, the team did not measure whether they matured to the infant level as in mice.
Both the mouse and human mini kidneys filtered blood and reabsorbed proteins such as albumin inside the mice. They also secreted kidney-specific hormones. In particular, the mouse mini kidneys even produced urine. However, because the structures that concentrate urine were insufficient, the urine was dilute. The human mini kidneys also appeared to be connected to the mice's circulatory system, but urine could not be collected.
Li Zhongwei said, "This assembloid is a revolutionary tool for studying kidney diseases, which affect one in seven adults," adding, "It will be a milestone on the path to providing artificial kidneys to the roughly 100,000 patients in the United States waiting for transplants."
The team created kidney organoids with a gene mutation that causes polycystic kidney disease. When transplanted into mice, the kidney organoids formed cysts like those of actual patients. Although researchers already study disease with organoids carrying the mutant gene, the organoids transplanted into mice also allowed observation of interactions between cysts and immune cells.
Melissa Little of the Murdoch Children's Research Institute at the Royal Children's Hospital in Australia told Science that it was "a beautiful paper," calling it "another advance that opens the way to designing more complex models from stem cells." Joseph Bonventre of Harvard Medical School said, "Existing organoids are fairly disorganized, whereas this study achieved organization," adding, "Kidneys grown in the lab could become the next-generation mainstay to replace patients' kidneys."
References
Cell Stem Cell (2025), DOI: https://doi.org/10.1016/j.stem.2025.08.013
Nature (2025), DOI: https://doi.org/10.1038/s41586-025-08808-3
Cell Stem Cell (2024), DOI: https://doi.org/10.1016/j.stem.2024.04.002
Nature Communications (2021), DOI: https://doi.org/10.1038/s41467-021-23911-5