While stem cell-derived kidney organoids promise to provide patient-specific models for disease research, and may even one day produce functional tissue for regenerative medicine, researchers have not yet been able to recreate the immense complexity of the organ’s patterning and functions.
Models tend to focus on either the kidney’s nephrons – functional units which filter blood and produce urine – or its collecting ducts, which concentrate urine and transport it to the bladder.
Now, researchers have brought these together in ‘assembloids’ which are the most mature and complex kidney structures grown in the lab to date.
Lab grown human kidney assembloid showing the formation of radial nephrons connected to a central collecting system. Credit: Pedro Medina, Li Lab
“This is a revolutionary tool for creating more accurate models for studying kidney disease, which affects one in 7 adults,” says corresponding author Zhongwei Li, associate professor of medicine, and stem cell biology and regenerative medicine at the University of Southern California, US.
“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 US awaiting transplant – the only cure for end-stage kidney disease.”
Li and collaborators grew mouse and human assembloids from kidney progenitor cells in the lab and then transplanted them into the abdomens of living mice. There, the assembloids matured further – growing larger and developing connective tissue and blood vessels.
The assembloids even displayed kidney-like functions within the body. They filtered blood, took up proteins such as albumin, secreted kidney hormones and exhibited the early signs of urine production.
“By maturing the assembloids in the native environment of the body, we tapped into kidney progenitor cells’ natural ability to self-assemble,” says Li. “We believe this will be a key to succeeding in the complex endeavour of building functional synthetic kidneys.”
Based on gene activity and other benchmarks, the researchers place their mouse assembloids at the same level of maturity as a newborn mouse kidney. A lack of newborn human kidney samples meant they could not determine the exact level of development for the human assembloids, though they did mature at least beyond the embryonic stage.
“Our study provides a powerful new tool for studying a wide range of complex kidney diseases, as well as strong foundation for engineering functional synthetic kidneys as a lifesaving option for the patients who need them,” says Li.
The research is presented in the journal Cell Stem Cell.