Without the use of fertilized eggs.
In the new study, the team set out to grow a synthetic embryo model solely from naïve mouse stem cells that had been cultured for years in a petri dish, dispensing with the need for starting with a fertilized egg. This approach is extremely valuable because it could, to a large extent, bypass the technical and ethical issues involved in the use of natural embryos in research and biotechnology. Even in the case of mice, certain experiments are currently unfeasible because they would require thousands of embryos, whereas access to models derived from mouse embryonic cells, which grow in lab incubators by the millions, is virtually unlimited.
Before placing the stem cells into the device, the researchers separated them into three groups. In one, which contained cells intended to develop into embryonic organs themselves, the cells were left as they were. Cells in the other two groups were pretreated for only 48 hours to over-express one of two types of genes: master regulators of either the placenta or the yolk sac. “We gave these two groups of cells a transient push to give rise to extra-embryonic tissues that sustain the developing embryo,” Hanna says.
Soon after being mixed together inside the device, the three groups of cells convened into aggregates, the vast majority of which failed to develop properly. But about 0.5 percent – 50 of around 10,000 – went on to form spheres, each of which later became an elongated, embryo-like structure. Since the researchers had labeled each group of cells with a different color, they were able to observe the placenta and yolk sacs forming outside the embryos and the model’s development proceeding as in a natural embryo.
These synthetic models developed normally until day 8.5 – nearly half of the mouse 20-day gestation – at which stage all the early organ progenitors had formed, including a beating heart, blood stem cell circulation, a brain with well-shaped folds, a neural tube and an intestinal tract. When compared to natural mouse embryos, the synthetic models displayed a 95 percent similarity in both the shape of internal structures and the gene expression patterns of different cell types. The organs seen in the models gave every indication of being functional.
The method opens new horizons for studying how stem cells form various organs in the developing embryo, and may one day make it possible to grow tissues and organs for transplantation using synthetic embryo models.