China grows first-ever fluorescent-green chimera monkey using stem cells

Scientists in China have created a monkey chimaera with two sets of DNA, which they believe will benefit medical research and the conservation of endangered species, reports CNN.

The monkey, which lived for 10 days before being euthanized, was created by fusing stem cells from a cynomolgus monkey — also known as a crab-eating or long-tailed macaque, a biomedical research primate — with a genetically distinct embryo from the same species. According to the researchers, this is the world's first live birth of a primate chimaera created with stem cells.

According to a proof-of-concept study published Thursday in the scientific journal Cell, the monkey was "substantially chimeric," with a varying but relatively high ratio of cells that grew out of stem cells throughout its body.

"It is encouraging that our live birth monkey chimera had a big contribution (of stem cells) to the brain, suggesting that indeed this approach should be valuable for modeling neurodegenerative diseases," said study coauthor Miguel Esteban, principal investigator at the Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, and researcher with BGI-Research Hangzhou, a nonprofit arm of Chinese genetics firm BGI.

""Monkey chimeras also have potential enormous value for species conservation if they could be achieved between two types of nonhuman primate species, one of which is endangered,," he went on to say. "If there is contribution of the donor cells from the endangered species to the germ line, one could envisage that through breeding animals of these species could be produced."

The term chimera comes from the monstrous hybrid creatures that populate Greek myths, but chimeric mice were developed in the 1960s and are now widely used in biomedical research.

Scientists can use chimeric lab mice to study how normal cells interact with genetically altered or mutated cells, which is useful for understanding biological processes and disease. However, there are limitations to mouse research that make pursuing efforts with monkeys worthwhile, according to the scientists.

"Mice don't reproduce many aspects of human disease for their physiology being too different from ours. In contrast, human and monkey are close evolutionary, so human diseases can be more faithfully modeled in monkeys," said senior study author Zhen Liu of the Chinese Academy of Sciences.

Human-animal chimeras, which contain some human cells as well as cells from other species, are more contentious. Scientists have created mouse embryos that are partially human, and in 2021, they reported growing human-monkey chimeric embryos.

Scientists hope that part-human chimeras will one day aid in the supply of organ transplants. Researchers reported in September that they had grown kidneys containing mostly human cells inside pig embryos.

Attempting to create a monkey-human chimera beyond the early embryonic stages of development, according to Liu, would be crossing an ethical red line.

The researchers cultured nine stem cell lines from 7-day-old monkey embryos. The cells were made pluripotent, which means they can organise into all the different cell types required to create a living animal.

They then chose a subset of cells to inject into genetically distinct 4- to 5-day-old monkey embryos. The cells were also infused with a green fluorescent protein, allowing the researchers to determine which tissues had developed from the stem cells.

After implanting the embryos into female monkeys, there were 12 pregnancies and six live births. According to the study, one of the born monkeys and one miscarried foetus were "substantially chimeric," with cells that grew out of stem cells throughout their bodies.

"This is an important study, but I wouldn't consider it's a breakthrough as the chimeras generated are not viable,"  Jun Wu, an associate professor of molecular biology at the University of Texas Southwestern Medical Centre, said.

He also stated that the team had not been able to show that the stem cells used to create the chimaeras were inheritable by offspring, which would be required to create monkey disease models for medical research. Wu was not involved in the research but has previously worked on human-animal chimaeras.

According to the study, the percentage of stem cells in monkey tissue ranged from 21% to 92%, with an average of 67% across the 26 different types of tissue tested. In brain tissue, the percentage was especially high.

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

"This study may contribute to easier and better making of mutant monkeys, just like biologists have been doing for years with mice," he said. "Of course, work with (nonhuman primates) is slower and much harder but is important."Hanna added.

Because of ethical concerns about animal welfare, the use of monkeys in scientific research is a contentious issue. According to the team, they followed Chinese laws as well as international guidelines governing the use of nonhuman primates in scientific research.

Penny Hawkins, the Royal Society for the Prevention of Cruelty to Animals' head of animals in science, stated that she is "deeply concerned about the inherent animal suffering and wastage associated with the application of these technologies to sentient animals."

She observed that 40 female macaque monkeys had embryos implanted, only 12 of which resulted in pregnancies. Six of these gave birth to live children, but only one had the desired genetic make-up. After 10 days, it was euthanized by a veterinarian due to respiratory failure and hypothermia.

According to a report released in May by a panel of the National Academies of Sciences, Engineering, and Medicine, research on nonhuman primates accounted for 0.5% of all animals used in scientific research in the United States.

The panel determined that research involving monkeys was critical to lifesaving medical advances, including the development of vaccines against Covid-19, due to their similarities to humans. The report also concluded that a lack of nonhuman primates had hampered research needed for public health and national security.