Researchers grow synthetic mouse embryo models from stem cells in an artificial womb
Starting only with stem cells, researchers from the Weizmann Institute of Science (Tel Aviv, Israel) have created synthetic mouse embryo models outside of the womb. The method provides new avenues for research into how stem cells form distinct organs during embryonic development and may one day allow for the growth of tissues and organs for transplantation using these artificial embryo models.
The research was headed by Jacob Hanna of Weizmann’s Department of Molecular Genetics, building upon two previous advances from Hanna’s lab. Firstly, was a method for reprogramming stem cells back to their naïve state, when their capacity to differentiate into various cell types is at its highest.
Secondly, the researchers utilized a technique, previously reported in Nature, that they designed for ex utero growth of natural mouse embryos. This method was previously successful in growing natural mouse embryos from day 5 to day 11. The technique involves the use of an electronically controlled device that simulates the uterine environment. It does this by replicating maternal blood flow to the placenta, bathing the embryos in a nutrient solution in continually moving beakers and tightly controlling oxygen exchange and atmospheric pressure.
Using these two techniques, the present study aimed to grow a synthetic embryo model solely from naïve mouse stem cells. The researchers first separated the naïve stem cells into three groups. Two of the groups were treated to overexpress one of two master regulator genes. One for the placenta and one for the yolk sack. “We gave these two groups of cells a transient push to give rise to extraembryonic tissues that sustain the developing embryo,” Hanna says. The last group of cells were left untreated as this group of cells would develop into the embryonic organs. The researchers also introduced colored labels to each cell type, enabling the observation of the different structures when they formed.
Upon mixing the three cell groups inside the device, aggregates began to form. Approximately 0.5% of the aggregates formed spheres, each of which later became elongated, embryo-like structures. The placenta and yolk sacs were visible outside the embryo, due to the labelling of these cell groups. The development stages of the synthetic embryos followed that of natural embryogenesis until day 8.5. At this stage, all the early organ progenitors were visible. This included the heart, blood stem cell circulation, the brain, the neural tube and the intestinal tract. The synthetic embryos also showed a 95% similarity to natural embryos in the shape of internal organs and the gene expression patterns.
Looking forward, Jacob Hanna stated, “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. And because our system, unlike a womb, is transparent, it may prove useful for modeling birth and implantation defects of human embryos.”
The results of this study could, in the future, facilitate a reduced dependence on natural embryos, bypassing numerous technical and ethical issues in research and biotechnology. This may make previously unfeasible research, that requires high numbers of embryos, possible by providing a potentially unlimited source.
Additionally, these synthetic embryo models represent a prospective source of cells, tissues and organs for transplantation. Hanna stated, “Instead of developing a different protocol for growing each cell type – for example, those of the kidney or liver – we may one day be able to create a synthetic embryo-like model and then isolate the cells we need. We won’t need to dictate to the emerging organs how they must develop. The embryo itself does this best.”
Source: Embassy of Israel (London) press release