Researchers have been able to create an artificial mouse embryo using two types of stem cells and a 3D scaffold, a milestone that could help scientists better understand the precarious early stages of embryo development in humans.
The successful approach taken by the research team at the University of Cambridge used both embryonic stem cells (ESCs), which eventually form a mammal's body, and extra-embryonic trophoblast stem cells (TSCs) that go on to form the placenta. The scientists used a combination of ESCs, TSCs and a 3D scaffold called an extracellular matrix to grow a self-assembling structure.
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"Both the embryonic and extra-embryonic cells start to talk to each other and become organized into a structure that looks like and behaves like an embryo," explains Cambridge Professor Magdalena Zernicka-Goetz, who led the research. "It has anatomically correct regions that develop in the right place and at the right time."
The team says that earlier attempts to grow embryos have struggled because they relied solely on ESCs, and the development process needs the different type of stem cells to be able to coordinate closely. Zernicka-Goetz says it's as if the different cells are telling each other where to go in order to form the embyro.
"These cells truly guide each other," she says. "Without this partnership, the correct development of shape and form and the timely activity of key biological mechanisms doesn't take place properly."
We've also seen other Cambridge researchers involved in research that grew mice egg cells in a lab.
Zernicka-Goetz's team compared their synthetic embryo's development to that of the real thing and found it followed the same pattern. The ESCs cluster at one end and TSCs at the other end, opening up two cavities in each sector that will eventually join to create a so-called pro-amniotic cavity where the embryo, and thereby the body, will start to take shape.
This is likely as far as this particular artificial embryo could go in terms of mirroring natural development, though. That's because it lacks a third type of stem cell that fuels the development of a yolk sac to provide nutrients for the embryo and a network of blood vessels. The researchers say that the genetically modified ESCs and TSCs have also not been optimized for a placenta to grow correctly.
Zernicka-Goetz has something else in mind for the artificial embryos: overcoming a shortage of natural embryos for research into human embryo development up to 13 days after fertilization. Her lab has developed a technique where blastocysts, the precursors to embryos, can develop in vitro past what would naturally be the implantation stage.
"We think that it will be possible to mimic a lot of the developmental events occurring before 14 days using human embryonic and extra-embryonic stem cells using a similar approach to our technique using mouse stem cells," she says. "We are very optimistic that this will allow us to study key events of this critical stage of human development without actually having to work on embryos. Knowing how development normally occurs will allow us to understand why it so often goes wrong."
The research was published in the journal Science.
Source: University of CambridgeView gallery - 3 images