• Research Without sperm, eggs or uterus: synthetic mouse embryos created in the laboratory
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No sperm, no eggs, no uterus. These are the future synthetic embryos that represent an important step towards a revolution in the field of tissue and organ transplants. From the Weizmann Institute of Science in Israel, Jacob Hanna, who belongs to one of the laboratories that has achieved this milestone, points out when explaining what this step consists of that "these are embryo models derived from stem cells instead of synthetic embryos as such; because people might think they're plastic."

To avoid the confusion and ethical problems that can arise from this scientific step, Hanna also points out that "we must remember that synthetic embryos are embryoids and not real embryos and do not have the potential to become viable (and in the mouse, when we put them back, they do not implant or continue)". With which it rules out the step of serving as a reproductive method.

In order to present this project, Hanna was a few days ago at the tenth edition of the Ivirma International Congress on assisted reproduction that took place in Malaga, where she explained that "embryoid models will also be useful to understand the basic principles of development and regeneration, and to identify pharmacological targets. and detect new therapies that can solve problems of early pregnancy (infertility, pregnancy loss, endometriosis, preeclampsia, etc.)".

The associate professor of the Weizmann Institute of Science pointed out during his participation in the event that "the embryo is the perfect starting point to generate organs and the best '3D bioprinter'. This is the key to being able to create mechanisms that allow us to make stem cells differ from the specialized ones in the body or directly form entire organs. To achieve this, it has been key to unleashing the potential for self-organization coding of stem cells."

Getting Started

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A synthetic embryo opens the door to obtaining all kinds of organs

  • Writing: SONIA MORENO Madrid

A synthetic embryo opens the door to obtaining all kinds of organs

One of the key steps besides the use of stem cells was to 'manufacture' the conditions of the uterus in the laboratory. Hanna explains, through an email to this medium, that "in our article published in Nature (2021) we unveiled the construction of an electronically controlled incubator device and also invented new growth media that were to support the natural development of mouse embryos outside the uterus during gastrulation (phase of formation of organ progeny) and organogenesis (from day 5 to day 11 of the uterus). mouse pregnancy lasting 20 days)". Last year, in September, they reported the success of the entire process in the journal Cell.

Development of complex embryos in half the time

The system devised by this laboratory reduces from 20 to 8 days the development of a kind of mouse embryo that has progenitor or specialized cells that give rise to a very complete list of functional organs: a heart with a beat, a brain with well-formed folds, a yolk sac, a neural tube, an intestinal tract, a placenta and incipient blood circulation. "Although the synthetic embryoids we manufacture are distinguished from embryos, they still have all organs rather than having just a specific region of organs (as is the case with organoids, for example)," Hanna said.

On the other hand, he adds that "in addition, the embryoid (synthetic embryo or sEmbryo as we call it) generates its own morphogens [which are the positional signals that control the fate of the cells in the embryo] in the right dose at the right time and in the right places. We do not introduce morphogens, embryonic ones are manufactured at the right time and magnitude. Everything is encoded inside."

The next step, says the researcher from the Department of Molecular Genetics of the Weizmann Institute, is to deepen the knowledge of the developed embryo. "Since we know what is needed to support the growth of the natural mouse embryo outside the uterus (device and conditions), we finally tested whether stem cells can generate an ab initio embryo from stem cells alone and which ones."

For that, Hanna explains that in the 'creation of the embryoids' they used the information of 27 pluripotent stem cells, "we do not use placental stem cells or yolk sac stem cells, but we show that everything can be done exclusively from iPS cell lines or induced pluripotent stem cells that are routinely used in laboratories around the world. This is a surprising finding in itself: it only starts with one type of cell, induced pluripotent cells that correspond to the early stages of development. Until a while ago, it was thought that established naïve cells could not give rise to functional trophoblasts that can drive development."

What will be the possible uses of advances in synthetic embryos?

In the long term, the most realistic goal is to research into how stem cells form various organs in the developing embryo to open new therapeutic horizons in organ transplantation. It would be a solution for tissue and organ culture using synthetic embryo models.

But in order to have the possibility of developing cells for therapeutic purposes, it is necessary to understand their mechanisms of reprogramming and differentiation, observing these transitions of stem cells during embryogenesis and organogenesis, in addition to studying the degree of equivalence of cells in vitro with those in vivo.

On the future and applications, Hanna points out that "our laboratory was the first to describe and optimize IPS conditions induced in humans. I have now founded a company (Renewal bio) that will focus on testing the possible clinical application of human synthetic embryoids based on induced human iPSCs. In Israel and many other countries, such as the US and UK, it is legal and we have ethical approval to do it with human iPSCs. This is providing an ethical and technical alternative to the use of embryos."

Hanna's breakthrough is in line with what the international team, led by scientists from the University of Cambridge (United Kingdom) and the California Institute of Technology (USA) achieved last August. Its development was then published in Nature, and then Magdalena Zernicka-Goetz's team was betting on the usefulness of the model to understand organogenesis, study the keys to development without resorting to experimental animals or having a resource for drug development, the researchers said.

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