Scientists create a chimeric monkey with two sets of DNA

Cao et al./Courtesy Cell

The monkey cells were injected with green fluorescent protein so that the researchers could identify which tissues grew from the stem cells.

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Scientists in China have created a chimera monkey with two sets of DNA, experimental work they say could ultimately benefit medical research and the conservation of endangered species.

The monkey, which lived for 10 days before being euthanized, was made by combining stem cells from a Cynomolgus monkey — also known as a crab-eating monkey or long-tailed macaque, a primate used in biomedical research — with a genetically distinct embryo from the monkey. The same types of monkeys. The researchers said this is the world’s first live birth of a primate chimera created using stem cells.

A proof-of-concept study details the research, which was published Thursday in the journal Scientific journal CellRemarkably, he said, the monkey was “largely chimeric,” having a varying but relatively high percentage of cells grown from stem cells throughout its body.

Miguel Esteban, co-author of the study and principal investigator at the Guangzhou Institute of Medicine, said: “It is encouraging that the monkey chimpanzee that was born alive had a significant contribution (of stem cells) to the brain, suggesting that this approach should indeed be of value in Modeling neurodegenerative diseases. Biomedicine and Health, Chinese Academy of Sciences and a researcher at BGI-Research Hangzhou, a non-profit arm of Chinese genetics company BGI.

“Chimeras also have enormous potential species conservation value if they can be achieved between two non-human species “The main species, one of which is threatened with extinction,” he added. “If there is a contribution of donor cells from endangered species to the germ line, one can imagine that by breeding animals of these species could be produced.”

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The term chimera originates from the monstrous hybrid creatures that populate Greek mythology, but chimeric mice were first created in the 1960s and have been commonly used in biomedical research.

Chimeric mice allow scientists to track how normal cells interact with genetically modified or modified cells, which is useful for understanding biological processes and diseases. But the scientists said there are limitations to research on mice, which makes continuing efforts with monkeys worthwhile.

“Mice do not reproduce many aspects of human diseases because their physiology is very different from ours. In contrast, humans and monkeys are close in evolution, so human diseases can be modeled more accurately,” said study senior author Chen Liu of the Chinese Academy of Sciences. In monkeys.

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Most controversial are human and animal chimeras, which contain some human cells, and some cells from other species. Scientists have Creating mouse embryos that are part humanAnd in 2021, scientists reported that they have Grown human chimeric embryos ape.

Scientists hope that half-human chimeras will one day help meet the demand for organ transplants. In September, researchers reported that they had done just that Mature kidneys that contain mostly human cells Inside pig embryos.

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Liu said in a press conference that trying to produce a human-simian chimera that goes beyond the early embryonic stages of development would be crossing an ethical red line.

The team cultured nine stem cell lines using cells taken from 7-day-old monkey embryos. The researchers made the cells pluripotent, giving them the ability to organize into all the different cell types needed to form a living animal.

They then selected a subset of cells to inject into genetically distinct 4- to 5-day-old embryos from the same species of monkey. The cells were also injected with green fluorescent protein so that the researchers could identify which tissues grew from the stem cells.

The embryos were implanted in female monkeys, resulting in 12 pregnancies and six live births. According to the study, one of the monkeys that was born and the fetus that was aborted were “largely chimeric,” containing cells grown from stem cells throughout their bodies.

“This is an important study, but I don’t consider it a breakthrough because the chimeric organisms generated are not viable,” said Jun Wu, an associate professor of molecular biology at the University of Texas Southwestern Medical Center.

He added that the team also was unable to prove that the stem cells used to generate the chimeras were heritable through offspring, which may be necessary to generate monkey disease models for medical research. Wu has not yet participated in the study He has worked on human and animal chimeras.

The percentage of stem cells in the monkey tissue ranged from 21% to 92%, averaging 67% across the 26 different tissue types tested, according to the study. The percentage was significantly high in brain tissue.

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“It’s a very good and important paper,” said Jacob Hanna, a professor of stem cell biology and embryology at the Weizmann Institute of Science in Israel, who was not involved in the study.

“This study may contribute to making mutant monkeys easier and better, just as biologists have done for years with mice,” Hanna added. “Of course, working with (non-human primates) is much slower and more difficult, but it is important.”

The use of monkeys in scientific research is a controversial issue due to ethical concerns about animal welfare. The team said it followed Chinese laws and international guidelines governing the use of non-human primates in scientific research.

Penny Hawkins, head of animal science at the Royal Society for the Prevention of Cruelty to Animals, said she was “deeply concerned about the inherent animal suffering and waste associated with applying these techniques to sentient animals.”

She noted that 40 female macaques had embryos implanted, of which only 12 led to pregnancy. Six of them resulted in live births, but only one had the desired genetic makeup. A veterinarian euthanized her 10 days later due to respiratory failure and hypothermia.

In the United States, research on non-human primates accounted for 0.5% of all animals used in scientific research, according to a report By a committee of the National Academies of Sciences, Engineering, and Medicine issued in May.

The committee found that research on monkeys, because of their similarity to humans, was crucial to life-saving medical advances, including the creation of vaccines against Covid-19. The report also concluded that the shortage of non-human primates has negatively impacted research essential for both public health and national security.

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