A group of scientists succeeded in creating 132 embryos by mixing genes from humans and monkeys: they survived 20 days and sparked an ethical debate

A group of scientists from the Salk Institute in California, USA, have successfully injected dozens of human stem cells into developing monkey embryos and the resulting hybrids survived for up to 20 days on laboratory plates.

These human monkey embryos could one day serve as useful models for human disease, embryonic development and aging, note the study authors in a new report, published April 15 in the journal Cell.

By zooming in on the interaction of human and animal cells in embryos, scientists could also learn how to help human cells survive among animal cells, which could advance the effort to grow human organs in living animal models.

Such studies would provide a possibility for human biology that would otherwise require experimentation with humans, which is currently not possible. Of course, the development of human-animal chimeras, organisms containing cells of at least two species, This raises its own ethical concerns, especially regarding how long these embryos should be allowed to develop.

In the past, scientists have attempted to incorporate human stem cells into pig and sheep embryos, with the ultimate goal of growing human organs in cattle for transplantation, the journal Science reported. But very few human cells survived the experiments.

The low survival rate could be due to the fact that pigs and sheep are not evolutionarily closely related to humans, said lead author Juan Carlos Izpisúa Belmonte, professor at the Institute of Studies organic products from La Jolla, Calif., in an email to Juan Carlos Izpisúa Belmonte. portal WordsSideKick.com. For example, pigs and humans have been diverging from each other for 90 million years, when they last shared a common ancestor, he said.

Because the researchers used monkeys in the new study, “the evolutionary distance is smaller, which may explain the greater relative efficiency of the integration of human stem cells into the chimera “. The new data collected from human and monkey embryos could provide clues on how to better cultivate human cells in more distant related animals, said Izpisúa Belmonte.

While this line of research can lead to exciting advancements in medical science, there are ethical concerns to be addressed, said Alejandro De Los Angeles, a stem cell biologist at Yale University School of Medicine, who has not participated in the study.

“One of the main concerns with human-animal chimeras is whether the ‘humanization’ of chimeras will occur, for example, if these chimeras acquire human-like cognition.” says From Los Angeles.

However, these concerns do not necessarily apply to the new experience, as the embryos were only allowed to develop for a limited time and were not implanted in a uterus. But for future studies, “It will be important to discuss the duration of the experiments”, He said.

Mixture of human and monkey cells

To produce the human monkey embryos, the researchers first collected oocytes, precursors of mature eggs, from Cynomolgus macaques (Macaca fascicularis), matured the cells in culture, and then injected them with macaque sperm for fertilize them. After six days, the fertilized cells have divided into additional cells, then assembled into hollow spheres, called blastocysts; In a normal pregnancy, a blastocyst would implant in the uterus and then give birth to a full-fledged embryo.

In this experiment, the team transferred the developing monkey blastocysts to lab plates and used a laser to remove their clear outer layer, called zona pellucida. Without an intact zona pellucida, the blastocysts adhere to the lab plate they are placed on, somewhat mimicking how they would implant themselves in the uterine wall. Then thThe team applied a technique developed by study co-author Weizhi Ji and his lab that allows monkey embryos to survive for 20 days outside the maternal body.; This technique involves making small adjustments to the culture solution that surrounds the cells.

Even so, the conditions do not perfectly mimic those found in a living organism, said Izpisúa Belmonte. “This … will have an effect not only on the development of the monkey embryos, but also on the human cells of the donor.”“, he claimed.

“Despite these considerations, it is really surprising that many embryos have developed over a long period”, added Izpisúa Belmonte.

Six days after the monkey cells were fertilized, the researchers injected 25 human stem cells into each blastocyst. These cells, called extended pluripotent stem cells (EPS), can differentiate into both embryonic tissue and “extraembryonic” tissue, which supports the developing embryo by providing nutrition and removing waste products.

All 132 embryos still contained human cells a day after implantation, but only 111 embryos successfully adhered to the lab plates. Of these, 103 embryos survived until day 10 after fertilization. Their numbers dropped dramatically between days 15 and 19, leaving only three surviving embryos at the end of the experiment.

More than half of the surviving embryos still contained human cells on day 9 and about a third still contained human cells on day 13. These human cells have integrated into the inner cell mass, the part of the blastocyst that gives rise to the embryo, the yolk sac, and the amnion (a protective membrane). The number of human cells that survived far exceeded that seen in a previous study, in which Izpisúa Belmonte and his colleagues injected human cells into pig embryos.

Ethical considerations

In addition to tracking the number of human stem cells that survived throughout the experiment, the team also looked at which genes were turned on in chimeric embryos during development and what proteins they produced. The team collected the same data from a set of unmodified monkey embryos to see if gene expression appeared different in the chimeric embryos.

“The authors … observed changes in monkey cells after human cells were introduced into the monkey embryo,” says From Los Angeles. “There has been interference between human and monkey cells. “

Compared to unmodified embryos, chimeric embryos activated additional genes and formed a different set of proteins. The authors hypothesize that some of these genes and proteins may be involved in “communication” between monkey and human cells, and that these lines of communication may be essential for the prolonged survival of human cells.

Going forward, the team plans to further investigate these communication channels. “To determine which are critical to the success of this process”, Says Izpisúa Belmonte. If these molecular changes could be replicated in other species, such as pigs, could potentially improve attempts at human tissue and organ development in these animalsadded.

When thinking about the future of chimeric embryos, scientific ethics should be part of the discussion, wrote Henry Greely, director of the Stanford Center for Law and Biosciences, and Nita Farahany, director of the Duke Initiative for Science and Society. , In a commentary on the new study. These embryos by their nature pose different problems from the direct transplantation of human cells and tissues into animals.

With direct transplantation, researchers can predict how the transplanted tissue will fit into the larger animal and can determine if a transplant might enter an area of ​​concern, such as the brain and gonads, they wrote. But in a chimeric embryo, human cells can potentially be incorporated throughout the body, assuming the embryo is allowed to develop for a period of time.

In new experiences, “The embryos here were not transferred to a uterus and therefore could not give birth to live chimeric animals or even fetuses,” and the growth of complete chimeras in a uterus is not the long-term goal of this research. “The implantation of human ape embryos would be ethically controversial and should be discussed by scientists, ethicists and the public before proceeding with such experiments.” says From Los Angeles.

In addition, scientists will need to seriously consider the welfare of animals involved in future research on chimeras, especially non-human primates, and also weigh the potential risks and benefits to humans, Greely and Farahany wrote. The National Academies of Science, Engineering and Medicine recently published a report outlining ethical considerations for the use of the human brain or nervous tissue in chimeras, but there has been little discussion of chimeric embryos. more broadly, they noted.

Now that human primate embryos can be cultured for extended periods of time, these discussions should take place as soon as possible.

* With Live Science information

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