Images showing the green fluorescence signals in different body parts of the live-birth chimeric monkey at the age of 3 days. Credit: Cell/Cao et al.
Key points:
- For the first time: live birth of a monkey that contains a high proportion of cells derived from a monkey stem cell line.
- The contribution of the stem cells in the different tissue types ranged from 21% to 92%.
- The researchers report an average of 67% across the 26 different types of tissue that were tested.
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.
This has previously been demonstrated in rats and mice but, until now, has not been possible in other species, including non-human primates.
The monkeys used in the study, which has been published in Cell, were cynomolgus monkeys, a primate common in biomedical research. The researchers first established nine stem cell lines using cells removed from 7-day-old blastocyst embryos. They then placed the cell lines in culture to give them enhanced ability to differentiate into different cell types.
The team performed a number of different tests on the cells to confirm they were pluripotent. The stem cells were also labeled 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, the researchers selected a particular subset of stem cells to inject into early monkey morula embryos (embryos that are 4–5 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 fetus that was miscarried were substantially chimeric, containing cells that grew out of the stem cells throughout their bodies. Both were male.
The scientists used gene sequencing and the green fluorescent protein label to determine which tissues contained cells derived from the injected stem cells. The study results showed 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% to 92%, with an average of 67% across the 26 different types of tissue that were tested. The numbers were lower in the monkey fetus. In both, stem cell-derived cells were detected in the testes and in cells that eventually develop into sperm cells.
The researchers said they plan to try to increase the efficiency of their new method by optimizing the culture conditions for the stem cells, the cultures for the blastocysts where the stem cells are inserted, or maybe even both. They also plan to further explore the mechanisms that underlie the survival of the embryos in the host animals, which will help improve the efficiency of chimera generation.