Kidneys grown in rats could pave the way for human transplant options

The researchers found that mouse stem cells produced apparently functional kidneys in the rat.

Scientists announced Wednesday that they have successfully used mouse stem cells to grow kidneys in rat embryos, using a technique that could one day help grow human kidneys for transplantation.

The researchers warned, however, that their success was only a first step and that there remained "serious technical obstacles and complex ethical issues" before the process could be used for human organs.

This technique has already been used to grow mouse-derived pancreas in rats, but this new study is the first evidence that it could one day solve the problem of mbadive donor kidney shortage in people with kidney disease .

The research, published Wednesday in the journal Nature Communications, began with the development of an appropriate "host" in which the kidneys could be grown.

The researchers collected genetically modified rat embryo structures so as not to develop kidneys by themselves.

Embryos were then injected with mouse pluripotent stem cells and implanted in the rat uterus to carry them to term.

Pluripotent stem cells are a kind of "master" cells that can grow in any cell or tissue that makes up the body.

The researchers found that mouse stem cells produced apparently functional kidneys in the rat.

But it was not the same when rat stem cells were injected into mouse embryos modified in the same way.

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"Rat stem cells do not easily differentiate into two main types of cells needed for kidney formation," said Masumi Hirabayashi, badociate professor at the National Institute of Physiological Sciences of Japan, who oversaw the 39; study.

Conversely, "mouse stem cells differentiate effectively … forming the basic structures of a kidney," he told AFP.

The reason for the difference is not yet entirely clear, but researchers believe that "environmental cues" in mice are probably responsible, rather than stem cells or technique.

But even in rat embryos, the technique was not without problems.

While rats developed apparently functional kidneys, including with appropriate connections to the ureter – tubes linking the kidneys to the bladder – they died shortly after birth because they were not properly nursing.

The elimination of genes that allow the kidneys to develop in utero seems to have also suppressed their sense of smell; the newborns did not detect any milk and died.

Their short life span meant that their kidney function could be subjected to limited testing, but Hirabayashi said the organs appeared functional "based on anatomical observations".

There are other concerns: the growth of a kidney in a host of another species could lead to a "contamination" of the organ by the host cells.

Ethical concerns

And the process of growing human organs in animals poses an ethical problem because human stem cells could turn into brain cells or reproductive organs of the host.

"The main ethical concerns are the risk of producing consciousness and / or gametes (reproductive cells)," Hirabayashi said.

"There are serious technical barriers and complex ethical issues that need to be discussed and resolved before producing human organs in animals," he added.

In the short term, more research is likely to focus on ways to genetically modify host rats without fatal side effects.

If successful, then researchers will want to do more testing on kidney derived stem cells and try to transplant hosts to other animals.

Finally, the tests could involve trying to grow human organs.

Pigs are generally considered the best hosts for the regeneration of human organs, but pork embryos only develop for 25 weeks, in contrast to the 40-week growth of human babies, which means that the species could not not suitable for the growth of organs in embryos.

Livestock, with a 40-week gestation, could be another option.

Hirabayashi said he hoped to see human organs develop in animal hosts during his lifetime.

"I do not know exactly the end of my life – tomorrow … Thirty years old … But I'm expecting a lot to hear about the practical application of organs hosted by animals."