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        16                                                                                HEALTH AND LABORATORY MAGAZINE













        EMBRYOS


        WERE PRODUCED


        WITHOUT USING


        SPERM AND EGGS!



        The embryos lasted longer

        than anticipated.





        An egg meets a sperm     organs, has proved far   mouse embryos from day 5   that sustain the developing   For Hanna and other
        – that’s a necessary first   more difficult.      to day 11.               embryo,” Hanna says.     stem cell and embryonic
        step in life’s beginnings. In                                                                       development researchers,
        embryonic development    “Until now, in most studies,   In the new study, the team   Soon after being mixed   the study presents a new
        research, it’s also a com-  the specialized cells were   set out to grow a synthetic   together inside the device,   arena: “Our next challenge
        mon first step. However, in   often either hard to pro-  embryo model solely from   the three groups of cells   is to understand how stem
        a new study, researchers   duce or aberrant, and they   naïve mouse stem cells   convened into aggre-  cells know what to do –
        from the Weizmann Insti-  tended to form a mishmash   that had been cultured   gates, the vast majority   how they self-assemble
        tute of Science have grown   instead of well-structured   for years in a petri dish,   of which failed to develop   into organs and find their
        synthetic embryo models   tissue suitable for trans-  dispensing with the need   properly. But about 0.5   way to their assigned spots
        of mice outside the womb   plantation. We managed to   for starting with a fertilized   percent – 50 of around   inside an embryo. And
        by starting solely with stem   overcome these hurdles by   egg. This approach is ex-  10,000 – went on to form   because our system, unlike
        cells cultured in a petri dish.   unleashing the self-organi-  tremely valuable because   spheres, each of which   a womb, is transparent, it
        That means they are grown   zation potential encoded in   it could, to a large extent,   later became an elongat-  may prove useful for mod-
        without the use of fertilized   the stem cells.”  bypass the technical and   ed, embryo-like structure.   eling birth and implantation
        eggs. This method opens                           ethical issues involved in   Since the researchers had   defects of human embry-
        new horizons for studying   Hanna’s team built on two   the use of natural embryos   labeled each group of   os.”
        how stem cells form various   previous advances in his   in research and biotech-  cells with a different color,
        organs in the developing   lab. One was an efficient   nology. Even in the case of   they were able to observe   In addition to helping
        embryo. It may also one   method for reprogramming   mice, certain experiments   the placenta and yolk   reduce the use of animals
        day make it possible to   stem cells back to a naïve   are currently unfeasible   sacs forming outside the   in research, synthetic em-
        grow tissues and organs   state – that is, to their   because they would require   embryos and the model’s   bryo models might in the
        for transplantation using   earliest stage – when they   thousands of embryos,   development proceeding   future become a reliable
        synthetic embryo models.  have the greatest potential   whereas access to models   as in a natural embryo.   source of cells, tissues, and
                                 to specialize into differ-  derived from mouse em-  These synthetic models   organs for transplantation.
        “The embryo is the best   ent cell types. The other,   bryonic cells, which grow in   developed normally until   “Instead of developing
        organ-making machine     described in a scientific   lab incubators by the mil-  day 8.5 – nearly half of the   a different protocol for
        and the best 3D bioprint-  paper in Nature in March   lions, is virtually unlimited.  mouse 20-day gestation   growing each cell type –
        er – we tried to emulate   2021, was the electroni-                        – at which stage all the   for example, those of the
        what it does,” says Prof.   cally controlled device the   Before placing the stem   early organ progenitors   kidney or liver – we may
        Jacob Hanna of Weiz-     team had developed over   cells into the device, the re-  had formed, including a   one day be able to create
        mann’s Molecular Genetics   seven years of trial and   searchers separated them   beating heart, blood stem   a synthetic embryo-like
        Department, who headed   error for growing natural   into three groups. In one,   cell circulation, a brain with   model and then isolate the
        the research team.       mouse embryos outside    which contained cells in-  well-shaped folds, a neural   cells we need. We won’t
                                 the womb. The device     tended to develop into em-  tube and an intestinal tract.   need to dictate to the
        Hanna explains that      keeps the embryos bathed   bryonic organs themselves,   When compared to natural   emerging organs how they
        scientists already know   in a nutrient solution inside   the cells were left as they   mouse embryos, the syn-  must develop. The embryo
        how to restore mature    of beakers that move     were. Cells in the other two   thetic models displayed   itself does this best.”
        cells to “stemness.” In fact,   continuously, simulating the   groups were pretreated for   a 95 percent similarity in
        pioneers of this cellular   way nutrients are supplied   only 48 hours to overex-  both the shape of internal   Reference: “Post-Gastru-
        reprogramming won a      by material blood flow to   press one of two types of   structures and the gene   lation Synthetic Embryos
        Nobel Prize in 2012. How-  the placenta, and closely   genes: master regulators   expression patterns of   Generated Ex Utero from
        ever, going in the opposite   controls oxygen exchange   of either the placenta or   different cell types. The   Mouse Naïve ESCs”, 1 Au-
        direction, that is, causing   and atmospheric pressure.   the yolk sac. “We gave   organs seen in the models   gust 2022, Cell.
        stem cells to differentiate   In the earlier research, the   these two groups of cells a   gave every indication of
        into specialized body cells,   team had successfully used   transient push to give rise   being function  DOI: 10.1016/j.
        not to mention form entire   this device to grow natural   to extraembryonic tissues                cell.2022.07.028
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