Take an egg, add sperm and wait, that's how mammals live. Two new papers show that there is more to it than meets the eye. Stem cells can divide and organize themselves on their own. Two groups have reported that they have grown synthetic mouse embryos for longer than before. A beating heart, a gut tube and neural folds are just some of the different organs that the embryo developed.
There is a process that isn't perfect. Only a small fraction of the cells develop these features, and those that do don't mimic a natural embryo. Scientists will be able to see organ development in unprecedented detail, thanks to the work. A bioengineer at the University of Michigan says this is very exciting. He believes that the next milestone will be a synthetic stem-cell based human embryo.
Two research teams did the same thing. A developmental and stem-cell Biologist with laboratories at the University of Cambridge, UK, and the California Institute of Technology in Pasadena has been working on this problem for a decade She says that they began with only embryonic stem cells. We couldn't take it any further because they can mimic early stages. Her team discovered a few years ago that when they added stem cells to their embryo, it grew further. They were able to culture embryos until day 7 last year. In the paper published in Nature today, the team describes how they grew the embryos.
A stem-cell biologist at the Weizmann Institute of Science in Israel has been working on this problem for a long time. A year ago, the team reported that they had developed a device that allowed them to culture natural mouse embryos for a long time outside the uterus. This incubator, which kept the embryos going from day 5 to day 11, takes aspects of a previous technology, in which the embryos reside in glass vials that rotates on a ferris wheel-like system. There is a mixture of oxygen and carbon dioxide going into the vials.
A year ago, his team shared part of their incubator with other biologists. He shared the brain of the machine with everyone who asked for it. In a paper published in Cell on August 1st, the team described how they used the system to grow embryos for 8.5 days. It takes about 20 days for a mouse to give birth.
It's long enough for the brain to grow, the heart to beat, and the neural and gut tubes to form. The synthetic embryos looked a lot like natural ones, but they weren't perfect. Some defects can be seen in the organ.
Each team grew their embryo by combining three different cell types and the other team created their embryo from nave stem cells. The process can be simplified by it. Everything can be started from a single population. In their Nature paper, the researchers used stem cells from a cell line to create the embryo.
The team knocked out a key part of the brain in an experiment. The mouse heads didn't develop correctly when they didn't have that genes. The result shows that the system is functioning.
Martin Pera is a stem-cell biologist at the Jackson Laboratory Center for Precision Genetics in Maine. There are two very skilled groups that can produce the same results.
Synthetic models have advantages over natural ones for research. They grow outside of the uterus, so they are easier to see. They can be manipulated using genome-editing tools. Fu says that they can knock out every possible mouse or human genes. They could be useful for discovering the role of different genes in birth defects. This model will be used by Zernicka-Goetz to understand why pregnant women fail.
Synthetic embryo development can be used to create new organs and tissues for people who need them.
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It will be difficult to translate this work into humans. Stem cells can be used to mimic some aspects of gastrulation when the early embryo organizes into distinct layers. The technical challenge to reach the stage of organ formation in human cells is significant. Ali Brivanlou is a developmental Biologist at Rockefeller University. The field is close.
The ethical concerns increase as the embryo becomes more advanced. The issue of whether these synthetic structures should be considered embryos is one of the key questions. The International Society for Stem Cell Research advises against culturing human embryos past day 14 in order to avoid the start of gastrulation. In 2021, the society removed the limit and issued news guidelines stating that such research should have a compelling scientific rationale and use the minimum number of embryos needed to achieve the scientific objective.
Pera believes there is a need for a continued discussion about the ethics of such models. Human embryo models have been worked on by researchers for a long time. He is worried about a backlash as human embryo models are developed. The field of research could be jeopardized by the reaction to that. Pera says that it is important for people to know what is being proposed. "We have to be careful."
The article was published on August 25th, 2022.
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