Human embryo replicas have gotten more complex. Here’s what you need to know
The lab-engineered models give scientists a look at human development beyond the first weekScience News talked to scientists and ethicists to learn more about⭕ these human embryo models.
What are human embryo models?
Before answering that question, Amander Clark, president of the International Society for Stem Cell Research, says we first need to understand that a human embryo is the product of fertilization of an egg and sperm. Embryo models, on the other hand, self-assemble from pluripotent stem cells — ones that have the power to make nearly any type of cell in the body. “Therefore, embryo models do not meet the clinical, medical or scientific definition of an embryo because they do not originate from the product of fertilization by two gametes,” says Clark, a stem cell scientist, developmental biologist and geneticist at UCLA.For years, scientists have studied the first week or so of human development using donated human embryos or esportiva bet:embryo models (SN: 1/5/22). From those, researchers learned a great deal about the formation of the ball 💛of cells kꦫnown as a blastocyst. Blastocysts have an outer layer of cells that will form the placenta and other support systems for the developing embryo, and an inner cluster of cells that will give rise to the body.
But it’s the next few weeks of life when the real action happens, says stem cell biologist and embryologist Jacob Hanna of the Weizmann Institute of Science in Rehovot, Israel. Between day seven and about day 35 after fertilization is when the embryo builds all its organs. “It moves from a ball of cells to a structure that anybody on the street … would tell you, ‘This is an embryo.’ And then the rest of the other eight months are just growth of the embryo,” he says. Researchers have assembled embryo models that contain some, but not all, of the types of cells necessary for normal development. The newly reported embryo models mimic structures that would be found in an embryo that has implanted in a uterus, even though the mimics have nothing to implant into. The models are simulating a very specific window of embryo development: “the events that occur as an embryo implants, how the embryo self-assembles,” Clark says. “Then essentially they collapse.” None of the models completely copy a real embryo, she says. For instance, none make a very good trophectoderm, the layer of cells that gives rise to the placenta later in development. That layer is important for an embryo to implant into the uterus, and it also sends signals that help the rest of the embryo develop properly.How did the latest buzz about embryo models start?
Post-implantation embryo models drew media attention when Żernicka-Goetz presented preliminary findings in the closing moments of a talk she gave June 13 in Boston at a meeting of the International Society for Stem Cell Research. The Guardian newspaper hailed the work as a breakthrough that created s꧙ꦍynthetic human embryos.
That characterization overstates the achievement, says Alfonso Martinez Arias, a developmental biologist at Pompeu Fabra University in Barcelona. The work is not a breakthrough, but an incremental advance, and is far from re-creating an embryo, he says.Żernicka-Goetz and colleagues genetically engineered human stem cells to resemble three types of cells necessary for embryo development: cells that mimic the important placenta-generating trophectoderm, cells that resemble ones that will form the yolk sac that feeds the embryo until the placenta takes over, and ones that form the epiblast — the cells inside the embryo that will develop into the body. The resulting balls of cells , the team reported June 27 in Nature.
For instance, the trophectoderm layer forms on the outside of the embryo-like structure as it does in embryos. But it doesn’t make proteins typical for that layer when assembled in a 3-D structure, so it isn’t truly a placental precursor, coauthor Bailey Weatherbee of the University of Cambridge said during the news briefing. But the layer is necessary for the rest of the embryo model to assemble, suggesting it performs some of the functions of the trophectoderm, she said.How were other embryo models made?
Like Żernicka-Goetz’s team, all the research groups started with human stem cells. Carefully controlling growing conditions and the numbers of certain types of cells added to the mix allowed the stem cells to grow into embryo-like structures. The models differ in the number of cell types they contain and in the features of real embryos they’re able to mimic.One group of researchers coaxed with two tissue layers. That work, also described June 27 in Nature, didn’t use genetic manipulation or chemicals to induce the stem cells to form embryo-like structures. Instead, the researchers r📖elied on stem cells’ ability to self-organize, says developmental biologist Berna Sozen of Yale School of Medicine.
The resulting model lacks the trophectoderm. When the researchers realized the tissue was missing, they thought its absence might tell them something about its importance, she says. “In the absence of these tissues you can see what will happen, what doesn’t happen, and then you [get] very strong scientific insights [about] why you need that tissue.” Another effort by researchers in China and Michigan, described in a not-yet-peer reviewed preprint posted June 16 online at bioRxiv.org, is , Martinez Arias says. But it still lacks a placenta precursor layer.Most recently, a team led by Jun Wu of the UT Southwestern Medical Center in Dallas persuaded stem cells to form that span the rearrangement event called gastrulation, the researchers report July 20 in Cell. During gastrulation♎ embryos go from hollow spheres of cells to multilayered structures that will givꦉe rise to organs and tissues that form the body.
These “peri-gastruloid” models made some tissues resembling those in the early nervous system and may help confirm the origins of cells that will give rise to eggs and sperm. These models also contain a yolk sac, but “our model is not a complete model,” Wu says. “We don’t have the placenta tissue.” Because the models lack the trophectoderm, the researchers had to add proteins to anchor and support the gastruloids so they could develop properly. A team of researchers in China reported preliminary results of similar June 28 at bioRxiv.org. That team found that the chemical thalidomide alters formation of the tissue layers and interrupts development. In the future, researchers might use such models to understand how chemicals from the environment could affect developing embryos, Wu says. Martinez Arias and others have previously made gastruloids that could model development up to day 19 after fertilization, but those earlier models didn’t have yolk sacs.