The model embryos were created from stem cells grown outside the uterus to a relatively late stage and demonstrate normal organ and tissue development.
An egg meeting a sperm is the basic condition for the creation of a new life. A new study by scientists from the Institute named after Cell was published in the scientific journal Cell. Weizmann challenges a basic fact of life. A research group led by Professor Yaakov Khan created for the first time artificial models of mouse embryos that developed from stem cells and grew outside the uterus - without fertilization of the egg by sperm. In addition to a breakthrough in the study of embryonic development, this innovative approach could open new avenues for future medicine, including growing organs and tissues that can be used for life-saving transplants.
On video an artificial mouse embryo on the eighth day of development is shown. You can see the beating heart, the yolk sac, the placenta, and the beginnings of blood circulation.
The artificial embryo model is based on two previous discoveries by the laboratory of Professor Han from the Department of Molecular Genetics at the Weizmann Institute: the first of which is an effective method of returning embryonic stem cells to the so-called "naïve" state - the very early stage of development in which stem cells have the ability to differentiate only in any type of tissue of the fetal body, but also in tissues outside the embryo, namely, in those that support the development of the fetus - the placenta and the yolk sac. The second discovery is an innovative method of growing mouse embryos outside the uterus until late stages of development. This method, developed over seven years of trial and error, is based, among other things, on a moving device in which the embryos are kept in laboratory beakers and surrounded by a nutrient solution. In the absence of blood flow from the mother to the placenta, the movement of the device imitates the natural nutrition of the fetus, while regulating the oxygen level and air pressure in the laboratory container. In a study published in March 2021 in the scientific publication Nature, it is stated that scientists managed to grow natural mouse embryos from 5 to 11 days with the help of this device.
A group of scientists. Right: Karin Jubran, Shadi Terzi, Alejandro Aguilera, Professor Yaakov Hana and Dr. Noah Nowerstern.
In the new study, scientists tried to develop an artificial model of mouse embryos — that is, embryos that do not come from a fertilized egg, as in the previous study, but from embryonic stem cells that have been grown for years in culture. To do this, scientists divided embryonic stem cells in the laboratory into three groups: one group, from which the embryo itself developed, this group was not subjected to any actions, and the other two groups were treated for 48 hours in order to increase the level of expression of certain genes necessary for the creation of tissues outside the embryo - the placenta in one group and the yolk sac in the second group. After the three groups were placed in a special device for artificially growing embryos, they quickly began to organize into clusters of cells, the vast majority of which did not develop properly. However, about 0.5% of them - 50 out of 10,000 - formed spherical tissues, which later developed into a fruit-like structure.
On video the operation of the device for growing mouse embryos outside the uterus is shown. The movement of the device simulates the natural feeding of the fetus, while simultaneously regulating the oxygen level and air pressure in the laboratory vessel.
The scientists pre-marked each group of cells with a different color and were thus able to see that the artificial models that succeeded in progressing really developed similarly to natural embryos, and the placenta and yolk sac were formed separately from the embryo. These artificial models of mouse embryos developed normally for 8.5 days – almost half of the 20-day gestation period – and they also formed internal organs that are the first to develop in an embryo, including the heart, the beginnings of blood circulation, a properly formed brain, primary versions of the central nervous system systems and the digestive system. The grown embryos demonstrated 95% correspondence to natural mouse embryos – both in the form of internal organs and in the nature of gene expression of various cell types.
Development of artificial embryos from day 1 (top left) to day 8 (bottom right).
The artificial model developed by the researchers opens new horizons in the study of embryonic development. "Our next challenge is to understand how stem cells know what to do - how they organize themselves into organs and how they find their way into the developing embryo. Also, because unlike the uterus, our system is transparent, we can use it to study birth defects and developmental defects, as well as to study various fertility problems,” Prof. Hana elaborates on future research directions.
Artificial embryo models can also reduce the number of animals used in research and in the future may even become a reliable source of cells, tissues and organs for transplantation. "The process of embryo development is actually a complex organ production mechanism – it's the ultimate biological 3D printer," says Professor Hana.
"Instead of developing a separate protocol for growing each type of cell, for example, kidney or liver cells, maybe in the future we can create an artificial model of the embryo and isolate the right cells from it. We will not dictate to the organs how they should develop - the embryo itself does it best."
This is an image of an eight-day-old mouse embryo - an artificial model (top) compared to natural development (bottom). Artificial embryos corresponded to natural mouse embryos by 95% - both in the form of internal organs and in the nature of gene expression of various cell types.
This research was carried out by specialists of the department of molecular genetics of the Institute: Shadi Terzi, Alejandro Aguilera and Karin Jubran. The study also involved Dr. Francesco Roncato, Emily Wildschutz, Dr. Bernardo Oldak, Alidette Gómez-Sizar, Nir Livnat, Serhiy Vyukov, Dmytro Lokshtanov, Segev Nava Tesa, Max Rose, and Dr. Noah Noverstern; Montester Hadad and Professor Zvi Lapidot from the Department of Immunology and Biological Regeneration of the Institute named after Weizman, Dr. Hadas Keren Shaul from the National Center for Personalized Medicine named after Nancy and Stephen Grand; as well as Dr. Nadir Ganam, Dr. Sohir Khana, and Dr. Itay Maza from Rambam Medical Center.
From scientific literature:
Artificial mouse embryos were developed from 27 stem cells, divided into 3 groups: the first group from which the embryo itself developed, and the other two groups were treated for 48 hours in order to increase the expression of genes necessary for the creation of tissues outside the embryo - the placenta and the yolk sac.
Link to the source:
