Scientists have successfully grown mouse kidneys inside rats – an advancement that may bring us one step closer to solving the donor organ shortage, a new study suggests.
The team at the National Institute of Physiological Sciences in Japan injected a type of stem cells that have the potential to become many other types of tissues from mice into pregnant rats bred to be missing their kidneys.
As their embryos – which should have also been missing kidneys – matured, the mouse stem cells developed into rat kidneys.
This means, in theory, that this method could be used to grow kidneys for one species, like humans, inside others, like livestock.
Such a method brings hope for the 100,000 or so people in need of transplants, but it would require significant resources and would certainly be a setback in the general trend away from animal testing.
Scientists in Japan have grown mouse kidneys in rats, suggesting that we could one day grown human kidneys in other animals, which could help combat the shortage of donated organs
Two years ago the Japanese team pulled off exactly the same feat with mouse pancreases.
But this is a more significant breakthrough.
Lead author Dr Teppei Goto, of the National Institute for Physiological Sciences, Aichi, explained: ‘We previously used blastocyst complementation to generate rat pancreas in mutant mice missing the organ.
‘We therefore decided to investigate whether the method could be used to generate functional kidneys, which would have much greater application in regenerative medicine owing to the high donor demand.’
Donor organs are in short supply as only around three in 1,000 people die in a way that makes them suitable as organ donors.
In the US, an average of 10 people a day die waiting for an organ transplant, and in the UK, nearly a third of people who need an organ wait more than two years in poor health, and one in 10 die before they get a transplant.
The shortage has prompted research into creating organs in the lab. Many of these methods involve stem cells.
Stem cells can turn into almost any type of tissue once exposed to the right chemical cocktails.
But growing large organs with complex three-dimensional structures and their own blood supply has proved far from easy.
Dr Goto and colleagues believe their results – achieved from just a few donor puripotent stem cells (PSCs) – have major implications for humans.
For patients in the final stages of kidney disease, a new organ is the only hope for regaining quality of life.
But, with 95,000 patients on the waiting list for a donor kidney in the US alone, the organs are in much higher demand than the donor supply can meet.
There are currently about 7,000 people in the UK awaiting a transplant. One in four will die before a suitable organ is found. Most are kidney patients.
So researchers have been working on methods to grow healthy organs outside the human body.
Using blastocytes to do so has already produced promising results.
The cells are formed several days after egg fertilization from mutant animals missing specific organs.
The primitive embryos are injected with stem cells from a normal donor – not necessarily of the same species.
In the new study, researchers took blastocytes from healthy mice and injected them into pregnant female rats bred to lack kidneys, and the rat’s offspring were born with kidneys they otherwise wouldn’t have had.
Initial attempts by the researchers to grow rat kidneys in mice proved unsuccessful, their PSCs did not readily differentiate into the two main types of cells needed for kidney formation.
A diagram from the study shows how scientists altered the genes of rats so they wouldn’t have kidneys (I), injected the pregnant rats with stem cells from healthy mice (II) and the result was chimeric rats with mice kidneys (bottom right)
But, when the reverse scenario was attempted, mouse stem cells efficiently developed inside rat blastocysts, forming the basic structures of a kidney.
Remarkably, more than two thirds of the resulting rat pups contained a pair of kidneys derived from the mouse stem cells that could be harvested and transplanted to other mice.
Further screening showed all of the organs were structurally intact, and at least half could potentially produce urine, reports Nature Communications.
Corresponding author Dr Masumi Hirabayashi said: ‘Our findings confirm inter-specific blastocyst complementation is a viable method for kidney generation.
‘In the future, this approach could be used to generate human stem cell-derived organs in livestock, potentially extending the lifespan and improving the quality of life of millions of people worldwide.’
This suggests that someone needing a new kidney or liver, for instance, could have what is essentially their own organ grown to order inside a specially conceived piglet, by providing a small skin sample.
Pigs or sheep make the best candidates, because their organs are a similar size to ours.
Dr Goto said: ‘The resulting kidneys appeared to be functional, providing proof-of-concept validation this approach could be used to generate human kidneys inside livestock.’
He added: ‘The chronic global shortage of donor kidneys leaves many end-stage kidney disease patients reliant on continued dialysis treatment.’
In January 2017 his team made worldwide headlines after announcing they had grown mouse pancreases inside rats.
When small parts of the organs were transplanted into mice with diabetes, it reversed their disease.
It was the first time this kind of inter-species organ generation had successfully treated a medical condition.
Then, last August, a US team predicted grow-your-own organs could be available for desperately ill patients within five years.
The team at the University of Texas Medical Branch (UTMB) successfully transplanted bioengineered lungs into pigs for the first time.
But Dr Goto said there are ethical issues to overcome concerning the creation of hybrid animal-human organs, called chimeras.
The technique would involve inserting human cells into pig embryos.
So the adult animals could have some human brain cells – raising the question of whether they should be afforded greater moral consideration.
Researchers may be able to avoid creating pig-human brains by using human stem cells that have been genetically altered so they are incapable of forming brain tissue.