A team of researchers in China has reported for the first time the live birth of a monkey that contains a high proportion of cells derived from a monkey stem cell line.
This “chimeric” monkey is composed of cells that originate from two genetically distinct embryos of the same species of monkey.
The feat has previously been achieved in rats and mice but, until now, has not been possible in other species, including non-human primates.
“This is a long-sought goal in the field,” said senior author Zhen Liu of the Chinese Academy of Sciences (CAS).
“This research not only has implications for understanding naive pluripotency in other primates, including humans, but it also has relevant practical implications for genetic engineering and species conservation. Specifically, this work could help us to generate more precise monkey models for studying neurological diseases as well as for other biomedicine studies,” Liu added.
In the study, published in the journal Cell, the team used cynomolgus monkeys, also known as crab-eating or long-tailed macaques, a primate common in biomedical research.
The investigators first established nine stem cell lines using cells removed from seven-day-old blastocyst embryos. They then placed the cell lines in culture to give them enhanced ability to differentiate into different cell types.
They performed a number of different tests on the cells to confirm that they were pluripotent — having the ability to differentiate into all of the cell types needed to create a live animal. The stem cells were also labelled with green fluorescent protein so the researchers would be able to determine which tissues had grown out of the stem cells in any animals that developed and survived.
Ultimately, they selected a particular subset of stem cells to inject into early monkey morula embryos (embryos that are four to five days old). The embryos were implanted into female macaques, resulting in 12 pregnancies and six live births.
Analysis confirmed that one monkey that was born alive and one foetus that was miscarried were substantially chimeric, containing cells that grew out of the stem cells throughout their bodies. Both were male.
The investigators used the green fluorescent protein label to determine which tissues contained cells derived from the injected stem cells. They also used gene sequencing and other tests to confirm the presence of stem-cell-derived tissue across different organs.
The tissue types they tested that contained the stem-cell-derived cells included the brain, heart, kidney, liver, and gastrointestinal tract. In the live monkey, the contribution of the stem cells in the different tissue types ranged from 21 per cent to 92 per cent, with an average of 67 per cent across the 26 different types of tissue that were tested. The numbers were lower in the monkey foetus.
In both animals, they also confirmed the presence of stem-cell-derived cells in the testes and in cells that eventually develop into sperm cells.
20231110159952
