Cao et al./Courtesy Cell
The monkey cells were injected with green fluorescent protein, allowing researchers to determine which tissues grew from the stem cells.
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China-based scientists have created a chimera of monkeys with two sets of DNA, and their experimental work could ultimately benefit medical research and endangered species conservation.
The monkey, which lived for 10 days before being euthanized, was created by combining stem cells from cynomolgus macaques, also known as cynomolgus macaques or long-tailed macaques, which are primates used in biomedical research, with embryos that are genetically distinct from cynomolgus macaques. Same type of monkey. Researchers say this is the world’s first living primate chimera made from stem cells.
A proof-of-concept study detailing the study was published Thursday. Scientific magazine “Cell”said the monkeys were notable for being “virtually chimeric”, containing a variable but relatively high proportion of cells grown from stem cells throughout the body.
“It is encouraging that our live monkey chimera made a significant (stem cell) contribution to the brain, suggesting that this approach may indeed be valuable for modeling neurodegenerative diseases.” ” said Miguel Esteban, study co-author and principal investigator at the Guangzhou Medical Research Institute. He is a researcher at the Department of Biomedicine and Health, Chinese Academy of Sciences, and he is also a researcher at BGI-Research Hangzhou, a non-profit arm of the Chinese genetics company BGI.
“Monkey chimerism, if achieved between two non-human species, could also be of great value for species conservation.” “One of these species is an endangered primate,” he added. “If donor cells from endangered species contribute to the germline, it would seem possible to produce these species through reproduction.”
Although the term chimera originates from giant hybrid creatures from Greek mythology, chimeric mice were first created in the 1960s and have been commonly used in biomedical research.
Chimeric laboratory mice allow scientists to track how normal cells interact with genetically modified or mutated cells, helping to understand biological processes and diseases. However, the scientists said the limitations of the mouse study made it worthwhile to continue research in monkeys.
“The physiology of mice is so different from ours that mice do not reproduce many aspects of human disease. In contrast, humans and monkeys are evolutionarily close, so monkeys do not reproduce many aspects of human disease.” We can model the disease more faithfully,” said Zhen Liu, senior study author from the Chinese Academy of Sciences.
Even more controversial are human-animal chimeras, which contain human cells and cells from other species.scientists Created mouse embryos that were partially humanAnd in 2021, scientists believe they Adult human-monkey chimera embryo.
Scientists hope that part-human chimeras may one day help meet the demand for organ transplants. In September, researchers a grown kidney containing mostly human cells inside a pig embryo.
At a press conference, Liu said any attempt to create monkey-human chimeras beyond the early stages of development would cross an ethical line.
The research team cultivated nine types of stem cell lines using cells taken from seven-day-old monkey fetuses. The researchers endowed the cells with pluripotency, giving them the ability to organize into the different cell types needed to produce living animals.
They then selected a subset of cells to inject into genetically distinct 4- to 5-day-old embryos from the same monkey species. The cells were also injected with green fluorescent protein so the researchers could determine what tissue had grown from the stem cells.
The embryos were implanted into female monkeys, and 12 of them became pregnant, and six gave birth. The study found that one of the monkeys born and one of the aborted fetuses were “virtually chimeras”, with their entire bodies containing cells grown from stem cells.
“This is important research, but we don’t consider it groundbreaking because the chimeras produced are not viable,” said Jun Wu, associate professor of molecular biology at the University of Texas Southwestern Medical Center.
He added that the research team has also not been able to prove that the stem cells used to generate the chimeras are inheritable to offspring, which is needed to generate monkey disease models for medical research. . Wu was not involved in the research, but I have been working on research on human-animal chimeras..
The study found that the proportion of stem cells in monkey tissue ranged from 21% to 92%, with an average of 67% across the 26 tissues tested. This proportion was particularly high in brain tissue.
“This is 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.
“Just as biologists have been working with mice for years, this work could help create easier and better mutant monkeys,” Hanna added. “Of course, the work[with non-human primates]takes longer and is much more difficult, but it is important.”
The use of monkeys in scientific research is a controversial issue due to ethical concerns regarding animal welfare. The research 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: “We are deeply concerned about the inherent suffering and wear and tear associated with applying these techniques to sentient animals.” Stated.
She pointed out that of the 40 female macaques implanted with embryos, only 12 became pregnant. Of these, she was able to give birth in six cases, but she had the desired genetic makeup in only one case. Veterinarians euthanized the animal 10 days later due to respiratory failure and hypothermia.
In the United States, research on nonhuman primates accounts for 0.5% of all animals used in scientific research. report According to a committee of the National Academies of Sciences, Engineering, and Medicine published in May.
The committee found that because monkeys are similar to humans, research in monkeys is critical to advances in life-saving medicine, including the development of vaccines against COVID-19. The report also concluded that the lack of non-human primates is negatively impacting research needed for both public health and national security.