Home Cellular science Scientists have created a mechanical uterus that can grow life in the lab

Scientists have created a mechanical uterus that can grow life in the lab

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The dystopian universe of blade runner features replicants or genetically modified people with sci-fi powers, such as super-strength and advanced intelligence, that far surpass any ordinary individual (albeit with a limited lifespan). Their invention is considered a colossal feat of scientific achievement (and the basis of a pretty messed up society).

But off the big screen, we’re still a long way from creating an organism — let alone a human — entirely from scratch. So far.

In a study published last month in the newspaper Nature, scientists in the United States, United Kingdom and Israel have succeeded in creating a synthetic mouse embryo without using an egg or sperm. Instead, they used an assortment of stem cells.

Compared to natural embryos maturing alongside them, these lab-grown counterparts developed similar features seen nearly nine days after fertilization, such as a beating heart, a very early-stage brain, and an intestinal tract – before abruptly stop growth.

“Essentially, the big question we grapple with in the lab is how do we start our lives?” said Magdalena Zernicka-GoetzPrincipal investigator of the study and a stem cell biologist at the University of Cambridge and the California Institute of Technology, during a press briefing.

Look in the “black box”

Researchers from the Weizmann Institute of Science in Israel have successfully grown synthetic (left) and natural (right) embryos side by side in the lab.Amadei and Handford

When a sperm fertilizes an egg, the fusion sets off a cascade of changes that cause the single cell to multiply, specialize, and organize into distinct cell types, tissues, organs, and other structures that make up a complete organism.

Over the past few decades, scientists have tried to recreate models of embryonic development in the lab to learn how the primordial phenomenon unfolds in real time. But this feat turned out to be extremely difficult. After all, we can’t just peer into a living uterus in the lab to directly observe microscopic events.

Specifically, researchers don’t know exactly what happens in the womb between about 14 days and a month of development, says Max Wilsona molecular biologist from the University of California at Santa Barbara, who was not involved in the study.

During this mysterious period, the brain builds and the heart sets. “It’s called the ‘black box’ of human development,” he explains.

This device took seven grueling years of engineering.

Recent efforts to unravel these mysteries have involved Hug human embryonic stem cells into blastocysts, a hollow, thin-walled ball of dividing cells that gives rise to the embryo during natural development.

This “blastoid” method hasn’t quite got scientists closer to how cells self-organize and specialize into organs. But in 2021, researchers from the Weizmann Institute of Science in Israel – who also worked on the new Nature study – developed a kind of mechanical matrix (image an axolotl tank at Frank Herbert’s Dunes).

This device took seven grueling years of engineering. It included an incubator, which floated and swirled the embryos in vials filled with a special nutrient-rich liquid. Meanwhile, a ventilator provided oxygen and carbon dioxide, meticulously controlling the flow and pressure of the gases.

With this setup, Weizmann researchers were able to grow stem cell-derived synthetic mouse embryos in their artificial mummy for around six days – until they were able to expand it further, according to a published study. earlier this month in the magazine Cell.

The embryos underwent gastrulation (when an early embryo changes into a multi-layered structure) for eight and a half days, but then stalled for unknown reasons. (A mouse pregnancy lasts about 20 days.)

But the experiment was not entirely a failure. He set out the colossal task of the latest study: to show that it was entirely possible to grow mammalian embryos outside the womb.

How to grow a baby

Zernicka-Goetz and her colleagues used embryonic stem cells, as well as those that give rise to the placenta and yolk sac, to grow synthetic embryos.José A. Bernat Bacete/Moment/Getty Images

Zernicka-Goetz, one of the authors of the new Nature study, has spent the past decade researching ways to develop synthetic embryos. She said her lab initially only used embryonic stem cells to mimic early development.

But in 2018, she and her colleagues discovered that if they added two more stem cells that give rise to the placenta (the organ that provides nutrients and removes waste) and the yolk sac (a structure that provides food early in development), the embryos were better prepared for self-assembly.

Here’s the problem with science: there’s always competition. After their 2018 Nature paper, the Zernicka-Goetz team was surprised when the Weizmann group released an incubator-ventilator system, along with subsequent experiments that forged embryos without sperm or eggs — exactly as they were attempting.

But science is also about collaboration. The two groups eventually teamed up to see if combining their techniques could result in the life-creating golden ticket.

The results were impressive: Zernicka-Goetz and her colleagues observed the uterine cells artificially transformed into synthetic “embroids” without any sort of modification or outside guidance.

The embryo model developed a head and a heart – parts of the body that researchers could never study in vitro.

Compared to natural mouse embryos that were cultured separately, these embryonic mice went through the same developmental stages up to eight and a half days after fertilization (just like the Weizmann team’s previous work), which is equivalent to the day 14 of human embryonic development.

The embryo model developed a head and a heart — parts of the body that researchers have never been able to study in vitro, Zernicka-Goetz said.

“This is truly the first demonstration of the forebrain in any model of embryonic development, and it has been a holy grail for the field,” co-author David Gloverprofessor-researcher in biology and biological engineering at Caltech, said during the press briefing.

Zernicka-Goetz’s team also tinkered with a gene called Pax6, which appears to be a key player in brain development and function. After removing Pax6 from mouse stem cell DNA using CRISPR, Zernicka-Goetz and colleagues observed that the heads of these synthetic embryos did not develop properly, mimicking what is seen when natural embryos lack this gene.

In humans, rare Pax6 mutations or deletions can lead to abnormal fetal development and death. They can also stimulate conditions such as aniridia (absence of the colored part of the eye, the iris) or Peters’ anomaly, which hinders the development of eye structures such as the cornea.

A chance for synthetic life?

Concocting synthetic embryos from human stem cells could prove a technical (and ethical) challenge.Westend61/Westend61/Getty Images

The detailed insight into early embryonic development could be a boon to human health. For example, it could help scientists understand why many pregnancies, whether conceived naturally or through assisted reproduction, fail early in the trimester.

Zernicka-Goetz said the research could also advance regenerative medicine. This could help scientists learn how to make viable, fully functioning replacement organs for a transplant patient using their own stem cells (potentially eliminating the need to use lifelong immunosuppressants).

Currently, we have a broad sense of organogenesis – or the development of an organ from embryo to birth – but we do not know all of the microscopic steps and cellular interactions that result in a fully functional organ.

The model system could help in the development of new drugs: it could reveal which drugs can be taken safely during pregnancy without harming the fetus. Now researchers can potentially test them on synthetic embryos, Zernicka-Goetz said.

“It is a breakthrough but at a very early stage of development, a rare event which, while superficially resembling an embryo, bears flaws that should not be overlooked,” Alfonso Martinez Ariasa developmental biologist at Pompeu Fabra University in Spain who was not involved in the study, said in a Press release.

A glaring challenge: While the synthetic mouse embryos look identical to their natural counterparts, their stalled development at eight and a half days makes it hard to say whether they would continue to develop properly.

“This is very strong proof that we will one day have this power, and it will be possible [to create synthetic life].”

So, despite its enormous potential, making synthetic embryos from stem cells is simply not possible at present.

“This blockade is not understood and must be overcome if one wishes to grow synthetic mouse embryos past the eighth day,” Christophe Galicheta stem cell biologist from the Francis Crick Institute in London who was also not involved in the new work, said in the same press release.

Since humans and mice do not share exactly the same characteristics when it comes to embryonic development, the next step is to possibly concoct synthetic embryos from human stem cells.

This is likely to prove complicated, more ethically than technically. But Wilson believes the research marks a major scientific milestone and a tool to add to humanity’s technological toolbox.

“This is very strong proof that we will one day have this power, and it will be possible [to create synthetic life]”Whether we decide to do it or not because of the ethics or even the potential benefits – that’s a question for society as a whole.”

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