Scientists from China have announced the birth for the first time in the world of a primate developed from embryonic stem cells from two different animals.
The advance, the researchers say, can contribute to the study of human diseases in the future, especially neurological diseases for which primates are the best animal models.
But they recognize that they will have to perfect the technique, since only two of the 91 embryos they created developed as chimeric animals - that is, with cells from different animals. One of them was never born and the other died when he was ten days old, according to the results of the research presented today in the journal Cell.
“This is a long-sought objective in this field,” Zhen Liu, co-director of the research from the Chinese Academy of Sciences, declared at a press conference, for whom “the use of chimeric primates is not an ethical concern.”
Along these lines, the Spaniard Miguel Ángel Esteban, who has lived in China since 2008 and also co-director of the research, added that “this study has followed all international regulations; (...) the regulations in China are very strict.”
The authors of the research aspire to have animals in the future that have cells with genetic alterations that are as similar as possible to human cells. To do this, they plan to genetically modify some cells and introduce them into viable embryos, creating chimeric animals. But first they must demonstrate that chimeric animals can develop and be born, something that had been achieved in rodents but never yet in primates.
In the research they present today, they have injected stem cells from a crab-eating macaque embryo, named for its love of eating crabs, into another embryo of the same species. The stem cells were obtained from a seven-day-old female embryo, in the blastocyst phase. They were injected into a five-day-old male embryo, in the morula phase.
The GFP (Green Fluorescent Protein) gene was added to the cells of the female embryo, which causes the cells to emit green light when they receive ultraviolet radiation. In this way it could be seen later, when the animal developed, which cells came from each embryo in its different organs and tissues.
Throughout the project, 74 embryos were implanted in the uteruses of 40 females. 12 pregnancies were achieved, of which only 6 prospered until the birth of a macaque. Of them, only one emitted green light, indicating that it was a chimeric animal. In the other five, the cells from the donor embryo had not implanted.
The fluorescent macaque emitted green light throughout its body, from head to tail. 67% of their cells came from the donor embryo. He had also incorporated fluorescent cells into his testicles, a relevant fact as it indicates that his descendants would also be chimeric and that chimeric animals could be bred for research.
But ten days after being born, the monkey's health rapidly deteriorated, he suffered respiratory failure and hypothermia, and was euthanized.
“The reason for working with monkeys is that they are more like humans than mice,” Zheng Lui said at the press conference. Among the diseases that could be investigated with chimeric monkeys, ALS (amyotrophic lateral sclerosis) stands out, since “it would be enough to manipulate a small percentage of motor neurons” to have a good animal model that reproduces what happens to patients.
Despite the premature death of the animal, “our results have important implications for the genetic engineering of non-human primates,” the researchers conclude in Cell. “The reproducible generation of chimeric monkeys (...) would represent a major advance for the field [of research], and our findings lay the foundation for achieving this goal.”
According to Miguel Ángel Esteban, “this work is another proof of how vibrant the stem cell field is becoming in China.”
