The first live birth of a chimeric monkey with a high proportion of cells derived from a stem cell line has been reported by researchers in China.
The monkey was born with cells derived from two genetically different cynomolgus monkeys — also known as crab-eating macaques — a monkey used in many biomedical studies.
After mice and rats, the monkey, born two years ago, is the first chimeric species in which a large number of cells are derived from an inserted embryonic stem cell line.
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The paper, published Thursday in the peer-reviewed journal Cell, found that the contribution of stem cell-derived stem cells ranged from about 20 to 90 percent, with a higher contribution in brain tissue.
„This work will help us develop more accurate monkey models for studying neurological diseases and other biomedical research,” said Liu Zhen, senior author of the paper from the Chinese Academy of Sciences (CAS). .
Liu said the research has the potential to protect the species.
To create the living chimeric monkey, the researchers first obtained nine stem cell lines from seven-day-old embryos. The cells were later confirmed to be pluripotent – meaning they could develop into the different cell tissues needed to form a living animal.
These cells were labeled with green fluorescent protein before being injected into early embryos, which were then implanted into female monkeys, according to the press release.
Of the 12 pregnancies, there were six live births. Only one chimeric male monkey was produced. The researchers reported that an aborted male fetus exhibited chimerism.
The team confirmed that the monkey and embryo were chimeric using a fluorescent protein label, along with experiments such as gene sequencing to determine the spread of stem cells to the monkey’s tissues. Across 26 different types of tissue, an average of 67 percent of the living monkey’s cells were derived from the injected stem cells.
Previous studies have reported monkeys with low levels of cells derived from stem cells, which „strictly speaking” cannot be considered chimeric, said Miguel A. Esteban, co-author and researcher at BGI Genomics and the Chinese Academy of Sciences. CAS), said at a press conference on Tuesday.
The monkey „has a very high contribution,” Esteban said [from the stem cells]Donor cells make up the bulk of the tissue [and] Complex structures throughout the monkey body … including the germ line”.
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The presence of stem cell-derived cells in the spermatozoa, which can develop into sperm, means that the genetic information inserted with the stem cells can be transferred to further generations.
Liu said the next application would be to model brain disease in tissues with a high contribution of stem cells — such as the brain.
According to Esteban, the method can also be used to create interspecies chimeras between extinct animals and similar non-extinct species. The resulting chimeric animals can be mated to pass on the extinct DNA.
„We have provided strong evidence that naïve monkey pluripotent stem cells have the ability to differentiate in vivo into all the different tissues that make up the monkey body,” Esteban said in the press release.
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Naive pluripotent cells can differentiate into all cell types required before implantation. These cells „have a higher growth potential because they are closer to earlier embryonic cells – transcriptionally and epigenetically,” Esteban said during the conference.
The team said there are research challenges to overcome. The efficiency of this method was low – out of 12 pregnancies they produced only one live chimeric monkey and one aborted chimeric fetus.
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The only surviving monkey deteriorated 10 days after birth and was eventually euthanized.
Scientists aren’t yet sure why this occurs, but epigenetic differences between cell types may be a factor, Liu told a press conference.
Esteban said that if the researchers can confirm that the monkeys survive after birth, they could contribute to the treatment of human diseases by creating complex disease models by changing multiple genes within a single monkey.