A team of scientists from China announced the world’s first birth of a monkey whose cells come from two genetically different embryos of the same species. Scientists have previously conducted similar studies in mice, but so far they have not been able to obtain chimeras in other species, especially primates.
The results and description of the research were published in the journal Cell (DOI: 10.1016/j.cell.2023.10.005).
Chimeras are organisms created from genetically different cells from at least two individuals. Chimerism can occur within species naturally, including in humans, although it is very rare. The monkeys used in the study were crab-eating macaques (Macaca fascicle), primates commonly used in biomedical research.
Scientists from the Chinese Academy of Sciences have for the first time created nine stem cell lines using cells taken from 7-day-old macaque embryos. They then placed the cell lines in culture to give them an increased ability to differentiate into different cell types. They performed a number of different tests on the cells to ensure they were multipotent, meaning they had the ability to differentiate into all the cell types needed to create a living animal. Stem cells were also labeled with green fluorescent protein.
Ultimately, the researchers selected a specific subset of stem cells that were implanted into embryos at 4-5 days of age. The embryos, in turn, were implanted into female macaques. The experiments resulted in 12 pregnancies. Six live monkeys were born. The analysis confirmed that a living monkey and an aborted fetus are essentially chimeric organisms and contain cells grown from stem cells grown in the laboratory. Both chimeras were male. The person who was born alive died within 10 days.
The researchers used a green fluorescent protein marker to identify tissues containing cells derived from the injected stem cells. They also used genetic sequencing and other tests to confirm the presence of stem cell-derived tissue in various organs. Green tracer is found in the brain, heart, kidneys, liver and digestive system. In both animals, scientists also confirmed the presence of stem cell-derived cells in the testes and in the cells that eventually develop into sperm.
The percentage of stem cells in various types of tissue ranged between 21%. Up to 92 percent. The researchers examined 26 different types of tissue for this purpose. Interestingly, the green mark was visible under UV light. In living chimeras, it was clearly visible in the eyes, but the fingertips had a faint glow in the light.
“We have provided strong evidence that monkey pluripotent stem cells have the ability to differentiate in vivo into all the tissues that make up the monkey’s body,” said Miguel Esteban of BGI Research and the Chinese Academy of Sciences, co-author of the study. “This study enhances our understanding of the developmental potential of pluripotent stem cells in primates,” he added.
“This is a long-awaited achievement,” said Chen Liu of the Chinese Academy of Sciences. “This study not only has implications for understanding pluripotency in other primates, including humans, but also has important practical implications for genetic engineering and species conservation,” he added. He added: “This work could help us produce more accurate monkey models for studying neurological diseases, as well as for other biomedical research.” Scientists could test some of the disease’s effects in monkey models in the future. It depends on the target, but the higher the proportion of donated stem cells in any target tissue, the more accurate the disease model will be.
Currently, the team is trying to improve the effectiveness of their method for generating chimeric monkeys.
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