Researchers created synthetic mouse embryos from stem cell, without eggs, sperm, or womb

• This is the first instance when stem cells have been used to make advanced-stage embryos
• The researchers have developed a special type of incubator that made this possible
• The technology could one day help provide cells, tissues, or even organs for transplantation.

In a major breakthrough, scientists in Israel have made mouse embryos without using sperm or egg cells but only stem cells taken from the skin, The Times of Israel has reported. These embryos have beating hearts as well as brain structures.

The discovery of stem cells and their ability to take the form of any cell type in the body has opened many doors in the field of medicine. From curing baldness to curing HIV, stem cells can be used everywhere.

However, sourcing stem cells has raised major ethical concerns. Found abundantly in the embryonic stages of cell growth, harvesting these cells requires the embryo to be destroyed before it is implanted in the female womb. So, researchers have been looking for an alternative way to source them and have even been successful in their search.

Making stem cells more "naive"

Studies have shown that stem cells are also present in small numbers in organs like the skin, which constantly undergoes renewal throughout our life. The process requires cells of different types, and that's where the multi-potency of stem cells comes in handy.

Jacob Hanna, a professor at the Molecular Genetics Department at the Weizmann Institute of Science in Israel, however, developed a method that would take back such stem cells to a previous step, where they are more "naive". In a previous study, Hanna and his team demonstrated that their technology could make human stem cells so "naive" that they could even be injected into mice, where they would function as if they were mice's own.

In separate work, Hanna's team also developed a special incubator that has all the necessary conditions for the growth of an embryo. In 2021, a group of researchers grew 250 mouse embryos into fetuses with fully formed organs inside this artificial womb. What Hanna and his team wanted to know was if the incubator could also grow embryos that were sourced from stem cells.

Embryos from stem cells

The researchers then used naive stem cells that had been cultured for years in a petri dish in the lab. Before placing them into the special incubator, these cells were divided into three groups. While one was left untreated to grow into embryonic stem cells, the other two were pretreated for a period of 48 hours to express genes that were master regulators of either the placenta or yolk sac.

The cells were once again mixed together in the incubator and allowed to grow. While most failed to develop properly, 0.5 percent, or 50 of 10,000 cells, went on to become spheres, which then took the elongated form of embryos.

The researchers had labeled each group of cells differently, so they could the growth of the placenta and yolk sac outside the embryo. At day 8.5, nearly half of the normal gestation of 20 days in mice, these embryos displayed early organs such as the beating heart, blood stem cell circulation, a brain with well-shaped folds, a neural tube,, and an intestinal tract, a university press release said.

This is the first instance of a research group using stem cells to make advanced embryos, Hanna told the Times of Israel. "Our next challenge is to understand how stem cells know what to do – how they self-assemble into organs and find their way to their assigned spots inside an embryo."

Apart from helping reduce the use of animals in stem cell research, the techniques developed in his lab could one day also help become a reliable source of cells, tissues, and organs for transplantation.

The findings of the study were published in the journal Cell.

Abstract

In vitro cultured stem cells with distinct developmental capacities can contribute to embryonic or extra-embryonic tissues after microinjection into pre-implantation mammalian embryos. However, whether cultured stem cells can independently give rise to entire gastrulating embryo-like structures with embryonic and extra-embryonic compartments, remains unknown. Here we adapt a recently established platform for prolonged ex utero growth of natural embryos, to generate mouse post-gastrulation synthetic whole embryo models (sEmbryos), with both embryonic and extra-embryonic compartments, starting solely from naïve ESCs. This was achieved by co-aggregating non-transduced ESCs, with naïve ESCs transiently expressing Cdx2- and Gata4- to promote their priming towards trophectoderm and primitive endoderm lineages, respectively. sEmbryos adequately accomplish gastrulation, advance through key developmental milestones, and develop organ progenitors within complex extra-embryonic compartments similar to E8.5 stage mouse embryos. Our findings highlight the plastic potential of naïve pluripotent cells to self-organize and functionally reconstitute and model the entire mammalian embryo beyond gastrulation.