A kidney-like organ grown from scratch in the lab has been shown to work in animals – an achievement that could be the prelude to growing spare kidneys for someone from their own stem cells.
Donated kidneys are in huge demand worldwide.
Christodoulos Xinaris of the Mario Negri Institute for Pharmacological Research in Bergamo, Italy, and his colleagues extracted cells from the kidneys of mouse embryos as they grew in the mother. The cells formed clumps that could be grown for a week in the lab to become “organoids” containing the fine plumbing of nephrons – the basic functional unit of the kidney. A human kidney can contain over 1 million nephrons.
Next, Xinaris’s team marinated the organoids in a chemical broth called vascular endothelial growth factor (VEGF), which makes blood vessels grow. Then they transplanted the organoids onto the kidneys of adult rats.
By injecting the rats with extra VEGF, the researchers encouraged the new tissue to grow its own blood vessels within days. The tissue also developed features called glomeruli, chambers where blood enters the nephrons to be cleansed and filtered.
The researchers then injected the animals with albumin proteins labelled with markers that give out light. They found that the kidney grafts successfully filtered the proteins from the bloodstream, proving that they could crudely perform the main function of real kidneys.
“This is the first kidney tissue in the world totally made from single cells,” says Xinaris. “We have functional, viable, vascularized tissue, able to filter blood and absorb large molecules from it. The final aim is to construct human tissues.”
“This technique could not be used clinically, but it shows a possible way forward for developing a functional kidney in the future,” says Anthony Hollander, a tissue engineer at the University of Bristol, UK. Although it will be several years before lab-grown tissues can benefit patients, the team says that the latest findings are a key milestone on the way.
Xinaris is currently working out how to add ducts to siphon urine to the bladder. So too are other groups. “We can now engineer kidneys with a proper drainage system,” says Jamie Davies at the University of Edinburgh, UK, who is a co-author on the Xinaris paper. “But we’ve not put these in animals yet.”
Cell sources needed
The other stumbling block is finding sources of human cells that will behave like the mouse embryonic kidney cells and self-assemble into complex kidney structures such as nephrons.
Obviously, says Davies, it is unethical to extract kidney embryonic cells from growing human embryos, but several potential cell sources are emerging. These include stem cells from amniotic fluid or the bone marrow, and adult cells such as skin cells converted in the lab into primitive kidney cells.
Both Davies and Xinaris are now working with human cells, incorporating them into the cultures of mouse cells that already grow into kidney tissue. Davies’s team is growing the kidneys within membranes taken from hen’s eggs, which allows them to view and manipulate the whole process.
The biggest question of all, however, is whether large enough grafts can be made to benefit patients. “We don’t know whether these little fetal kidneys could grow large enough to become fully functioning tissue in humans,” says Davies.