Mini kidneys grown in the lab were transplanted into test animals and succeeded in filtering blood and producing urine. Until now, researchers had made kidney cells from stem cells and grown them in 3D, but this is the first time multiple tissues each performed their respective functions. The work is expected to open a new path for research and treatment of kidney disease.
A team led by Professor Zhongwei Li of the Keck School of Medicine at the University of Southern California (USC) said on the 18th in the international journal Cell Stem Cell that it had developed an Organoid that combines the kidney's blood filtration and urine concentration functions.
Organoid means a "mini organ" and refers to a structure grown from stem cells—which can develop into any human cell—into a three-dimensional form resembling an organ. The researchers said this Organoid is the most mature and complex among lab-grown kidney constructs to date and could serve as a tool for developing new treatments.
◇ Assembloid that connects each part of the kidney
Scientists test potential drugs on human cells when developing new medicines. Although this better reflects human responses than animal testing, it did not reveal organ-level effects. Cells grown in a dish cannot reflect an organ's 3D structure. Organoid, known as a mini organ, solved this problem.
The USC team created kidney Organoids from stem cells. In particular, they did more than grow a single cell type in 3D; they grew different cells and connected them. The result was an organoid assembly, a so-called assembloid. An assembloid can demonstrate actual organ function. In May, a team at the Stanford University School of Medicine released 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 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 microscopic tubules that filter blood and then reabsorb the water and nutrients the body needs are intricately connected.
The filtration unit of the kidney is the nephron, and the tissue that concentrates urine and sends it to the bladder is the collecting duct. The USC team had previously released collecting duct and nephron Organoids in international journals in 2021 and 2024, respectively, but this is the first time they have cultured an assembloid that contains both tissues.
The researchers first differentiated mouse and human stem cells to create precursor cells for the nephron and collecting duct, respectively. These are progenitor cells. When they combined nephron progenitor cells with collecting duct progenitor cells and cultured them, the kidney's 3D structure emerged. The team transplanted these mouse and human kidney assembloids into mice.
Inside the mice, the assembloids matured further and grew in size. Connective tissue and blood vessels, which connect and support various tissues and organs, also developed. Li said, "By maturing the assembloids in a bodily environment, we allowed kidney progenitor cells to self-assemble naturally," adding, "This approach will be the key to successful artificial kidneys."
◇ Implemented kidney functions of filtration and urine production
Kidney Organoids reported until now were at the embryo level. That is because they stopped at differentiating embryonic stem cells into kidney cells and growing them in 3D.
By contrast, genetic analysis showed that the kidney Organoids transplanted into mice this time matured to the level of a newborn mouse kidney. The human kidney Organoids also matured beyond the embryonic stage in the mouse body, but due to a lack of newborn samples, the team could not measure whether they matured to the infant level as in mice.
Both 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 structures that concentrate urine were insufficient, the urine was dilute. The human mini kidneys also appeared to have been connected to the mouse circulatory system, but urine could not be extracted.
Li said, "This assembloid is a revolutionary tool for studying kidney disease, which affects one in seven adults," adding, "It will be a milestone on the path to providing artificial kidneys to more than 100,000 patients in the United States waiting for transplants."
The team created kidney Organoids with a gene mutation that causes polycystic kidney disease. The kidney Organoids transplanted into mice formed cysts like those in actual patients. While researchers already study disease using Organoids with mutant genes, 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 called it "a beautiful paper" in Science and noted it was "another advance that opens the way to designing more complex models from stem cells." Joseph Bonventre of Harvard Medical School said, "Whereas existing Organoids are quite disorganized, 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