Researchers create synthetic mouse embryos in artificial womb

Researchers at the Weizmann Institute of Sciences in Israel created synthetic Mouse Embryos, without using sperm or egg, After growing them in a artificial uterus for eight days, which opens a door to the possible creation of replacement organs for humans.

“The goal is not to create mice or babies outside the womb, but rather to advance understanding of how organs develop in embryos and use that knowledge to develop new ways to heal people,” the researchers said.

From a pool of embryonic stem cells, scientists created synthetic embryos that they closely resembled real mouse embryos, with beating hearts, blood circulation, folded brain tissue, and intestinal tracts. The mouse embryos grew in an artificial uterus and stopped developing after eight days, about one-third of a mouse’s pregnancy.

The advance, which a decade in the making, arrives in a field abuzz with efforts to develop embryo models from human and mouse cells. Scientists can use such models to observe the early stages of embryonic development and study how organs are formed.

The research, published Monday in the journal Cell, is far from growing a mouse, let alone a human, outside the womb. Although the synthetic mouse embryos closely resembled the natural mouse embryos, they were not exactly the same and they did not implant or result in pregnancy in real mice.

“The embryo is the best machine for making organs and the best 3d bioprinter: we try to emulate what it does”, said the head of the research team, Professor Jacob Hanna, from the Department of Molecular Genetics at the Rehovot Institute.

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What does this mean for the future?

The method opens new horizons to study how stem cells form various organs in the developing embryo and may one day make it possible to grow tissues and organs for transplant using synthetic embryo models.

Hanna’s team built on two previous advances in her lab. One was an efficient method of reprogramming stem cells to their earliest stage, when they have the greatest potential to specialize into different cell types.

The other, described in a scientific article in ‘Nature’ in March 2021, was the electronically controlled device that the team had developed over seven years of trial and error to growing natural mouse embryos outside the womb.

The device keeps the embryos bathed in a nutrient solution inside continuously moving beakers, simulating the way nutrients are supplied by material blood flow to the placenta, and closely controls oxygen exchange and atmospheric pressure.

In previous research, the team had successfully used this device to grow natural mouse embryos from day five to day 11.

In the new study, the team set out to grow a synthetic embryo model solely from naive mouse stem cells that had been grown for years in a Petri dish, without starting with a fertilized egg.

“This approach is extremely valuable because it could, to a large extent, circumvent technical and ethical issues related to the use of natural embryos in research and biotechnology,” the researchers noted.

Even in the case of mice, certain experiments are currently infeasible because would require thousands of embryos, while access to models derived from mouse embryonic cells, which grow in laboratory incubators by the millions, is practically unlimited.

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Synthetic models developed normally until day 8.5, nearly half of the mouse’s 20-day gestation, by which time all the first organs had formed, including a beating heart, circulating blood stem cells, and a brain with well-formed folds, a neural tube, and an intestinal tract.

Compared to natural mouse embryos, synthetic models showed a similarity of 95%, both in the shape of the internal structures and in the gene expression patterns of different cell types. The organs seen in the models gave every indication of being functional.

For Hanna and other stem cell and embryonic development researchers, the study presents a new platform. “Our next challenge is understand how stem cells know what to do, how are they formed in the organs and find their way to assigned points within an embryo,” he explains.

“And because our system, unlike a uterus, is transparent, it may be useful for modeling birth and implantation defects in human embryos,” he added.

The models of synthetic embryos not only minimize the use of animals in researchbut could also become a reliable source of cells, tissues and organs for transplantation.

“Instead of developing a different protocol for culturing each type of cell, for example kidney or liver cells, we may one day be able to create a synthetic model similar to an embryo and then isolate the cells we need.” Author.

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