A breakthrough that could potentially benefit medicine and the conservation of endangered species, but which raises certain ethical issues.
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The chimeric monkey, at the age of three days.
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A chimeric monkey, whose cells come from two genetically distinct embryos of the same species, was created by Chinese bioengineers whose work is published in the journal Cell (New window)(en English).
Professor Zhen Liu and his colleagues at the Associated Reproductive Engineering Laboratory of the Chinese Academy of Sciences created the chimera from embryonic stem cells. This is the first full-term birth of a primate chimera created using this type of pluripotent stem cell.
These cells have the capacity to become any cells of the body, so that they represent a great interest for regenerative medicine, in order to create tissues or organs, but also to model diseases.
< p class="StyledBodyHtmlParagraph-sc-48221190-4 hnvfyV">The cynomolgus monkey, a macaque commonly used in biomedical research, was euthanized 10 days after birth, according to guidelines from the International Society for Stem Cell Research .
Until today, chimeric mice and rats have been created and are even used in the laboratory to generate genetic models. However, attempts at chimerism in other species, including non-human primates, have not been very successful due to their biological complexity and longer gestation and maturation times.
In their work, the Chinese team tested various cell culture conditions to optimize their procedures for preparing chimeric primate embryos.
She thus created nine lines of stem cells from seven-day-old monkey embryos. She also placed a green fluorescent protein there to facilitate their monitoring.
These lines were then injected into primate embryos and implanted into female monkeys .
The experiment generated an aborted fetus and a living chimeric monkey. Both were males.
Results show that cells derived from donor stem cells integrated efficiently, ranging from 21% to 92%, in the 26 different types of tissues (brain, heart, liver, kidneys, etc.) taken from the chimera monkey.
On average, integration reached 67% of the tissues tested in the chimeric monkey.
In addition, in both monkeys, the researchers also confirmed the presence of cells derived from stem cells in the testicles and in the cells that develop into sperm, opening the door to creating generations of chimeric monkeys.
The percentages were, however, lower in the aborted fetus.
Our results represent a proof of principle that we can indeed create chimeras. They provide strong evidence that monkey pluripotent stem cells have the ability to differentiate in vivo into all the different tissues that make up a monkey's body, Professor Zhen Liu said in a statement.
This breakthrough not only has implications for our understanding of pluripotency in other primates, but it will eventually have practical implications for the fields of genetic engineering and species conservation, since chimeras may be made between two non-human primate species, one of which is endangered.
A quote from Zhen Liu, Chinese Academy of Sciences
The researchers' goal is to one day create chimeras that model human diseases: if the inserted stem cells carry genomes associated with a specific disease, researchers will then be able to study their behavior in an organism.
This work could help us generate more accurate monkey models for studying neurological diseases as well as other biomedical studies, Zhen Liu believes.
His colleague Miguel Esteban, also from the Chinese Academy of Sciences, is particularly encouraged by the results regarding the brain.
It is encouraging to note that our chimera was born with a significant contribution (of stem cells) to the brain, which suggests that this approach could be useful for modeling neurodegenerative diseases.
A quote from Miguel Esteban, Académie Chinese science
Until then, in the coming years, the Chinese team will try to better understand the mechanisms that promote the survival of embryos in host animals to possibly create several generations of chimeras.
This is a very important paper that could help make it easier and better to create mutant monkeys, just as biologists have been doing for years with mice, Israeli biologist Jacob Hanna told CNN , from the Weizmann Institute, which did not participate in the work.
Working with non-human primates is certainly slower and much more difficult, but it is also very important.
A quote from Jacob Hanna, Weizmann Institute
Obviously, the use of animals in this type of research is not without ethical concerns related to their well-being.
The Chinese team declares in its work to respect Chinese laws and international guidelines governing the use of non-human primates. humans in research.
However, Briton Penny Hawkins, director of the Royal Society for the Prevention of Cruelty to Animals, expressed concern about the animal suffering and waste inherent in the application of such technologies to sentient animals, when an interview with CNN.
She recalled that a veterinarian still euthanized the chimera after 10 days.
Last May, an expert report from the American Academies of Sciences, Engineering and Medicine showed that non-human primates accounted for 0.5%. of all animals used in research.
Experts said that research on monkeys, because of their similarities to humans, was essential to achieving breakthroughs essential medical conditions, particularly in the creation of vaccines against COVID-19.
