wp-plugin-hostgator domain was triggered too early. This is usually an indicator for some code in the plugin or theme running too early. Translations should be loaded at the init action or later. Please see Debugging in WordPress for more information. (This message was added in version 6.7.0.) in /home4/scienrds/scienceandnerds/wp-includes/functions.php on line 6114ol-scrapes domain was triggered too early. This is usually an indicator for some code in the plugin or theme running too early. Translations should be loaded at the init action or later. Please see Debugging in WordPress for more information. (This message was added in version 6.7.0.) in /home4/scienrds/scienceandnerds/wp-includes/functions.php on line 6114Source:https:\/\/www.quantamagazine.org\/embryo-models-challenge-legal-ethical-and-biological-concepts-20230613\/#comments<\/a><\/br> Embryo models might offer a way to go down that path with even fewer legal and ethical restrictions. They are not legally considered to be embryos because they do not have the potential to grow into viable organisms. So even under present guidelines and regulations in many countries, if embryo models can be grown through gastrulation and beyond, it could become legal for the first time to experimentally study human development and perhaps lead to a better understanding of defects that cause miscarriages or deformities.<\/p>\n But if embryo models can indeed grow that far, at what point do they stop being models and become equivalent to the real thing? The better and further along the models get, the blurrier the biological and ethical boundaries become.<\/p>\n That dilemma was hypothetical when embryo models could only recapitulate the very earliest stages of development. It isn\u2019t anymore.<\/p>\n Embryo models are generally made from embryonic stem cells, \u201cpluripotent\u201d cells derived from early embryos that can develop into every tissue type in the body. By the time an embryo has reached the blastocyst stage \u2014 around day 5 or 6 in human development \u2014 it consists of several cell types. Its hollow shell is made of cells that will form the placenta (called trophoblast stem cells, or TSCs) and the yolk sac (the extra-embryonic endoderm, or XEN cells). The pluripotent cells that will become the fetus are confined to a blob on the inside of the blastocyst wall, and it is from them that embryonic stem cells can be cultured.<\/p>\n Experiments in the 1990s and early 2000s showed that embryonic stem cells extracted from one blastocyst and transferred into another can still become an embryo capable of developing all the way to full-term birth as a healthy animal. But the support provided by TSCs and XEN cells is essential \u2014 embryonic stem cells alone can\u2019t get past the first few days of development unless they are in a blastocyst.<\/p>\n More recent research, however, shows that embryolike structures can be made from scratch from the respective cell types. In 2018, Zernicka-Goetz and her colleagues showed that assemblies of embryonic stem cells, TSCs and XEN cells from mice could self-organize into a hollow form shaped like a peanut shell and comparable in appearance to a regular embryo undergoing gastrulation. As gastrulation proceeded, some of the embryonic stem cells showed signs of getting more specialized and mobile as a prelude to the development of internal organs.<\/p>\n But those early embryo models were flawed, Zernicka-Goetz said, because the added XEN cells were at too late a developmental stage to wholly fulfill their role. To solve that problem, in 2021 her group found a way to convert embryonic stem cells into early-stage XEN cells. \u201cWhen we placed [embryonic stem cells], TSCs and these induced-XEN cells together, they could now undergo gastrulation properly<\/a> and initiate development of organs,\u201d she said.<\/p>\n Last summer in Nature<\/i>, Zernicka-Goetz and her collaborators described how they had used a rotating bottle incubator to extend the growth<\/a> of their mouse embryo models by another crucial 24 hours, to day 8.5. Then the models formed \u201call regions of the brain, beating hearts and so on,\u201d she said. Their trunk showed segments arising for development into different parts of the body. They had a neural tube, a gut and the progenitors of egg and sperm cells.<\/p>\n In a second paper published around the same time in Cell Stem Cell<\/i>, her group induced embryonic stem cells to become TSCs<\/a> as well as XEN cells. Those embryo models, cultivated in the rotating incubator, developed to the same advanced stage.<\/p>\n Meanwhile, Hanna\u2019s team in Israel was growing mouse embryo models in a similar way, as they described in a paper in Cell<\/em><\/a> that was published shortly before the paper from Zernicka-Goetz\u2019s group. Hanna\u2019s models too were made solely from embryonic stem cells, some of which had been genetically coaxed to become TSCs and XEN cells. \u201cThe entire synthetic organ-filled embryo, including extra-embryonic membranes, can all be generated by starting only with na\u00efve pluripotent stem cells,\u201d Hanna said.<\/p>\n Hanna\u2019s embryo models, like those made by Zernicka-Goetz, passed through all the expected early developmental stages. After 8.5 days, they had a crude body shape, with head, limb buds, a heart and other organs. Their bodies were attached to a pseudo-placenta made of TSCs by a column of cells like an umbilical cord.<\/p>\n \u201cThese embryo models recapitulate natural embryogenesis very well,\u201d Zernicka-Goetz said. The main differences may be consequences of the placenta forming improperly, since it cannot contact a uterus. Imperfect signals from the flawed placenta may impair the healthy growth of some embryonic tissue structures.<\/p>\n Without a better substitute for a placenta, \u201cit remains to be seen how much further these structures will develop,\u201d she said. That\u2019s why she thinks the next big challenge will be to take embryo models through a stage of development that normally requires a placenta as an interface for the circulating blood systems of the mother and fetus. No one has yet found a way to do that in vitro, but she says her group is working on it.<\/p>\n Hanna acknowledged that he was surprised by how well the embryo models continued to grow beyond gastrulation. But he added that after working on this for 12 years, \u201cyou are excited and surprised at every milestone, but in one or two days you get used to it and take it for granted, and you focus on the next goal.\u201d<\/p>\n Jun Wu<\/a>, a stem cell biologist at the University of Texas Southwestern Medical Center in Dallas, was also surprised that embryo models made from embryonic stem cells alone can get so far. \u201cThe fact that they can form embryolike structures with clear early organogenesis suggests we can obtain seemingly functional tissues ex utero, purely based on stem cells,\u201d he said.<\/p>\n In a further wrinkle, it turns out that embryo models do not have to be grown from literal embryonic stem cells \u2014 that is, stem cells harvested from actual embryos. They can also be grown from mature cells taken from you or me and regressed to a stem cell-like state. The possibility of such a \u201crejuvenation\u201d of mature cell types was the revolutionary discovery<\/a> of the Japanese biologist Shinya Yamanaka, which won him a share of the 2012 Nobel Prize<\/a> in Physiology or Medicine. Such reprogrammed cells are called induced pluripotent stem cells, and they are made by injecting mature cells (such as skin cells) with a few of the key genes active in embryonic stem cells.<\/p>\n So far, induced pluripotent stem cells seem able to do pretty much anything that real embryonic stem cells can do, including growing into embryolike structures in vitro. And that success seems to sever the last essential connection between embryo models and real embryos: You don\u2019t need an embryo to make them, which puts them largely outside existing regulations.<\/p>\n Even if embryo models have unprecedented similarity to real embryos, they still have many shortcomings. Nicolas Rivron<\/a>, a stem cell biologist and embryologist at the Institute of Molecular Biotechnology in Vienna and one of Zernicka-Goetz\u2019s collaborators, acknowledges that \u201cembryo models are rudimentary, imperfect, inefficient and lack the capacity of giving rise to a living organism.\u201d<\/p>\n The failure rate for growing embryo models is very high: Fewer than 1% of the initial cell clusters make it very far. Subtle abnormalities, mostly involving disproportionate organ sizes, often snuff them out, Hanna said. Wu believes more work is needed to understand both the similarities to normal embryos and the differences that may explain why mouse embryo models haven\u2019t been able to grow beyond 8.5 days.<\/p>\n Still, Hanna is confident that they will be able to extend that limit by improving the culture device. \u201cWe can currently grow [IVF] mouse embryos ex utero until day 13.5 \u2014 the equivalent for human embryos will be around day 50 to 60,\u201d he said. \u201cOur system opens the door.\u201d<\/p>\n He added, \u201cWhen it comes to studying early human development, I believe this is the only possible way.\u201d<\/p>\n
\n\u2018Embryo Models\u2019 Challenge Legal, Ethical and Biological Concepts<\/br>
\n2023-06-15 21:58:08<\/br><\/p>\nTurning Stem Cells Into Embryos<\/b><\/h2>\n
Growing Organs in the Lab<\/b><\/h2>\n