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  • The Best Clinic
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    Israeli Scientists Create Artificial Embryos

    The embryo model was created from stem cells grown outside the uterus until a relatively late stage and demonstrates normal organ and tissue development.

    The ovum meets the sperm – this is the main condition for new life creation. Published today in the scientific journal Cell, a new study by scientists from the Weizmann Institute challenges a basic fact of life. A research team led by Professor Yaakov Khan the first time created for artificial models of mouse embryos that developed from stem cells and grew outside the uterus – without ovum sperm fertilizing. In addition to providing breakthroughs in the study of embryonic development, this innovative approach could open up new avenues for future medicine, including growing organs and tissues that could be used for life-saving transplants.

    The video shows an artificial mouse embryo on the eighth day of its development. You can see the heart beat, yolk sac, placenta and the start of circulation.

    The artificial embryo model builds on two previous discoveries from Professor Khan’s laboratory in the Department of Molecular Genetics at Weizmann Institute of Science: the first of which is an effective method for returning embryonic stem cells to a so-called “naive” condition – the earliest development stage in which stem cells have the ability to differentiate without only in any type of fetal body tissue, but also in tissue outside the embryo, namely, in placenta and yolk sac that support the development of fetus. The second discovery is an innovative method of growing mouse embryos outside the uterus until later stages of development. The method, developed over seven years of trial and error, relies, among other things, on a moving device in which embryos are held in beakers and surrounded by a nutrient solution. In the absence of blood flow from mother to placenta, the movement of the device imitates natural nutrition of fetus, while regulating the oxygen level and air pressure in laboratory container. A study published in March 2021 in scientific publication Nature indicated that scientists were able to grow natural mouse embryos from days 5 to 11 using this device.

    A group of scientists. from right: Karin Joubran, Shadi Terzi, Alejandro Aguilera, Professor Yaakov Hana and Dr. Noah Noverstern

    In new study, scientists tried to develop an artificial model of mouse embryos – that is, embryos that do not come from a fertilized ovum, as in previous study, but from embryonic stem cells that have been grown in culture for years.

    To do this, scientists divided embryonic stem cells in laboratory into three groups: one group, from which 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 them to create tissues outside the embryo – placenta in one group and yolk sac in the second group. After the three groups were placed in a special embryo-growing device, they quickly began to organize themselves 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 that eventually developed into a fetus-like structure.

    The video shows the operation of a rotating device for growing mouse embryos outside the uterus. Movement of the device simulates natural feeding of fetus, while simultaneously adjusting the oxygen level and air pressure in laboratory vessel.

    Previously Scientists designated each group of cells with a different color and thus were able to see that artificial models that managed to develop did indeed develop similarly to natural embryos, and placenta and yolk sac formed separately from embryo. These artificial mouse embryo models developed normally within 8.5 days – which is almost half of 20-day gestation period – and also developed the internal organs that are the first to develop in an embryo, including a heart beat, the beginning of circulation, a properly formed brain, primordial versions central nervous system and digestive system. The grown embryos demonstrated 95% correspondence to natural mouse embryos, both in the shape of internal organs and in the pattern of gene expression of different cell types.

    Development of artificial embryos from day 1 (top left) to day 8 (bottom right). Normal development of early internal organs was observed, including a heart beat, the onset of circulation, a normally shaped brain, primary versions of central nervous system, and digestive system.

    The artificial model developed by the researchers opens new horizons in the study of embryonic development. “Our next challenge is the necessity to understand how stem cells know what they need to do – how they organize into organs and how they find their way into the developing embryo. “In addition, 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,” Professor Hana details directions for future research.

     

     

    Artificial embryo models can also reduce animals application in research and even become a reliable source of cells, tissues and organs for transplantation in future. “The embryo development process 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, such as kidney or liver cells, perhaps in future we will be able to create an artificial embryo model and isolate the desired cells from it. We will not dictate to organs how they should develop – this is best done by the embryo itself.”

    This is an image of the eighth day of life of a mouse embryo – an artificial model (top) compared to natural development (bottom). Artificial embryos were 95% similar to natural mouse embryos – both in the shape of internal organs and in nature of gene expression of different cell types.

    This study was carried out by specialists from the Institute’s Department of Molecular Genetics: Shadi Terzi, Alejandro Aguilera and Karin Joubran. Also participating in the study were Dr. Francesco Roncato, Emily Wildschutz, Dr. Bernardo Oldak, Alydette Gomez-Cesar, Nir Livnat, Sergey Vyukov, Dmitry 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 Weizmann Institute, Dr. Hadas Keren Shaul from the National Center for Personalized Medicine. Nancy and Stephen Grand; and also, Dr. Nadir Ghanam, Dr. Sohir Khana and Dr. Itai Maza from the Rambam Medical Center.

    From scientific literature

    The artificial mouse embryos developed from 27 stem cells divided into three groups: the first group from which the embryo itself developed, and the other two groups were treated for 48 hours to increase the expression of genes necessary to create tissues outside the embryo – the placenta and yolk sac.

    Source link: https://heb.wis-wander.weizmann.ac.il/life-sciences/n-11743

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