Rat and human chimeras will be created in Japan

Scientists will try to grow a human pancreas in rat embryos

Ivan Shunin, "The Attic"

The Japanese authorities approved the application of biologist Hiromitsu Nakauchi for experiments on growing animal embryos to which human stem cells were planted. Such experiments are needed in order to further cultivate organs in animals for transplantation to humans.

The idea of using animals as an organ donor, not another person, is not new: in the history of medicine, experiments with xenotransplantation have been attempted repeatedly, but none of these operations can be called completely successful. Perhaps the most famous example is the case of Stephanie Beauclerk, or "Baby Faye", who had a baboon heart transplanted in 1984. 21 days after the operation, she died due to transplant rejection.

There are biomedical startups that are trying to "bring this procedure to mind" by working with pigs and primates. For example, the famous geneticist George Church in 2015 founded the startup eGenesis, which uses molecular genetics to assemble to "refine" pigs in order to "create an alternative source of safe and effective organs, tissues and cells compatible with humans."

Now xenotransplantation is prohibited in most countries of the world. Therefore, such studies have been conducted so far only with animals of other species. For example, at the end of last year, an international group of researchers reported that during their experiment, two baboons out of 14 lived with a heart from a GM pig for six months.

There is an alternative to this path – not to transplant animal organs, but to use animals, such as pigs and primates, as "incubators" for human organs. For this GM animals that do not develop any of the organs can be transplanted either human germ cells or induced human pluripotent cells (iPS cells) so that they form a missing organ in the animal's body, already human. Experiments on the creation of such chimeras in countries with developed biotechnologies have been limited to varying degrees until recently.

Last March, a moratorium expired in Japan, which limited work with animal embryos containing human cells to 14 days. March 1st Ministry of Education, Culture, Sports, Science and Technology Japan has officially allowed its scientific groups to conduct laboratory experiments on growing human organs in animals. In announcing this decision, Nature magazine mentioned biologist Hiromitsu Nakauchi, who has not hidden his desire to do such research for quite a long time. He has already created embryos of genetically modified pigs without a pancreas and transferred induced human pluripotent cells into them in the hope that they differentiate into human liver cells in the pig's body.

Immediately after the lifting of the moratorium in Japan, Nakauchi, who practices mainly at the American Stanford (where he also has his own laboratory), applied for experiments on planting human stem cells in embryos of rats and mice whose genome would have been specially edited so that they would not develop a pancreas. Nature reports that the scientist is not going to immediately try to bring the matter to the birth of such chimeras, but will start by working with embryos that have passed the two-week deadline. After that, he will receive permission to experiment with pig embryos.

In 2017, Nakauchi's group successfully grew a mouse pancreas from induced pluripotent cells in a rat, and then transplanted the organ of a mouse with diabetes. The donor organ took root and thus saved the mouse from the disease. In 2018, scientists tried to consolidate their success, this time with human iPS cells and sheep without a pancreas, but failed: by the twenty-eighth day of development, there were almost no pluripotent human cells left in embryos, and nothing remotely resembling a pancreas had formed. Nakauchi then summarized that the failure was most likely due to the fact that the genetic difference between sheep and humans was too great. Now, he says, the permission of the Japanese authorities will allow him to "attack this problem."

Experiments on the humanization of animals are extremely ethically charged procedures, so Nakauchi separately stipulates that if the proportion of human cells in the brain of the chimeric embryos tested exceeds 30%, he will terminate the experiment, Asahi Shumbun reports.

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