Science. For the first time, they create human pseudo-embryos from skin cells

 Science.  For the first time, they create human pseudo-embryos from skin cells

Science. For the first time, they create human pseudo-embryos from skin cells

MADRID.- A team of scientists, led by the Argentine biochemist José Polo, has created human pseudo-embryos without using eggs or sperm, but from reprogrammed skin cells to return to an embryonic state. The advance, in the shifting frontiers of bioethics, forces society to have a conversation as soon as possible: What legal status do these little balls of cells have that mimic a human embryo but are not?

The Argentine researcher flees from the term artificial embryo. “We don't want to raise false expectations or make people think that we're going to have a clone army in a year. The technology hasn't gotten to that yet," says Polo, from Monash University in Melbourne, Australia.

The biochemist narrates the first days after fertilization, when the egg and the sperm form a single all-powerful cell, with the instructions to become a person with 37 billion cells. On the first day after fertilization, the embryo only has two cells. The second day there are already four. The third, eight. And around the sixth day, a structure of just over 0.1 millimeters and about 200 cells called a blastocyst is formed. “It's like a soccer ball with a tennis ball inside. The soccer ball, when implanted in the uterus, is what will generate the placenta. And the tennis ball is what the baby is going to generate”, explains Polo.

The Argentine team has taken skin cells and rewound them to a stage similar to that of natural blastocyst cells, which are capable of giving rise to a multitude of other specialized cells: blood, liver, muscle, brain. . Put in contact, these reprogrammed cells interact and in six days form a human pseudo-embryo, a structure the size of a grain of sand that the authors call the induced blastoid or iBlastoid. A single experiment can produce thousands.

Limit

Polo's group has grown these pseudo-embryos in the laboratory to the equivalent of a natural blastocyst of about 11 days. The international consensus, established in research with human embryos left over from fertility clinics, marks a red line of 14 days, the moment at which an embryo can no longer divide to give rise to twins. On day 14 the concept of individual could already be handled, although the reality is that up to 75% of successful fertilizations are lost in those first two weeks of pregnancy, according to data from Polo.

Human pseudo-embryos open the black box of embryonic development, difficult to access due to obvious ethical limits. "The iBlastoids can serve as a model for the first two weeks, so we can study which mutations or which toxins cause this process to fail", says the researcher. His progress is published today in the journal Nature. Another scientific team, led by the Chinese molecular biologist Jun Wu, announces in parallel in Nature the creation of human pseudo-embryos from embryonic stem cells, derived from natural blastocysts, thanks to the optimization of culture protocols in the laboratory.

Ciencia. Por primera vez, crean pseudoembriones humanos a partir de células de la piel

It is the first time that complete models of the human embryo have been generated, according to the Spanish biologist Marta Shahbazi, from the University of Cambridge, in the United Kingdom. The researcher believes that this is the first step in a "revolution" that will finally allow us to understand the secrets of human development. “They are not embryos, this has to be very clear. They are simply models, which can help us study specific mechanisms that we cannot study with the embryo”, emphasizes Shahbazi, whose team managed in 2016 to cultivate human embryos outside the uterus, in the laboratory, for longer than anyone before: 13 days.

The human pseudo-embryos generated by the teams of José Polo and Jun Wu are not functional, they disintegrate with the passing of days. The equivalents in mice, implanted in the uterus of females, are also not viable. Everything points to the fact that human pseudo-embryos are incapable of giving rise to a baby or anything like it. Shahbazi believes that "there is no ethical problem" in studying these structures beyond the 14-day red line. “There is no legislation that establishes the limits for this type of research, because it is something very new, but clearly limits will be set. These embryo models, right now, could not generate an entire organism, but who knows if that will be achieved in 10 or 15 years”, says Shahbazi.

Debate

The team of the Spanish biologist Alfonso Martínez Arias generated last year, from embryonic cells grown in the laboratory, structures similar to a human embryo between 18 and 21 days old, but without the seed of the brain or the tissues that would form the placenta. Martínez Arias, then at the University of Cambridge, is one of the international references who in 2018 urged to debate the ethical aspects of research with human embryo models.

The biologist believes that the two new studies are "a step forward, but not a great achievement", because both models still present functional and structural differences with real embryos, in addition to foreign cells that should not be there. “The ultimate goal is to replace the early embryo with these structures that avoid the ethical problem of having to rely on embryos. One cannot go around pulling human embryos as if buying pipes, ”he sentences.

Martínez Arias, who recently joined the Pompeu Fabra University in Barcelona, ​​believes that future embryo models, already perfected, will have to be regulated by the same ethical rules as real embryos. The biologist, however, is in favor of erasing the 14-day red line, provided there is good scientific justification and studying case by case. “You have to do it carefully. If it goes up like an open bar I think it will generate a lot of cheesy headline-seeking science instead of serious science,” he warns.

Research with human embryo models is boiling. The Chinese Jun Wu, now at the University of Texas (USA), already collaborated with the Spanish Juan Carlos Izpisúa in the creation in 2019 of artificial mouse embryos from a single ear cell. And two other leading laboratories, those of the Polish Magdalena Zernicka-Goetz and the Chinese Yang Yu, have also presented in recent days the preliminary results of their models of human embryos.

The jurist María Casado, founder of the Bioethics and Law Observatory of the University of Barcelona, ​​already defended in 2000 research with leftover embryos from assisted reproduction clinics. In her opinion, the key is the idea of ​​gradualness. “Do we give the same importance to a person, to a viable fetus, to an in vitro embryo, to a germ cell [egg or sperm precursor] and to a skin cell? Protection has to be gradual, you can't look for all-or-nothing solutions”, she says. Casado asks to "de-dramatize" and favor research that generates benefits for human health. “If with a skin cell we are able to make an embryo, we are not going to protect the skin cells as if they were viable embryos”, she ditches.

Casado, holder of the UNESCO Chair in Bioethics at the University of Barcelona, ​​is also in favor of revising the current 14-day rule. "We cannot pretend to regulate things once and for all, as if it were written in heaven," she says.

©El País, SL

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