2023-04-22 13:25:01
The latest findings in Assisted reproduction may be key to the creation of tissues and organs that can be used in the future in tissue and organ transplants, as has been revealed in the 10th International IVIRMA Congress, held in Malaga.
Specifically, researchers led by Dr. Jacob Hanna, from the Department of Molecular Genetics at the Weizmann Institute of Science, created mouse synthetic cells without developmental restrictions and discovered potential for embryonic and extraembryonic development on electronically controlled uterus-simulating platforms, thus generating embryos complete with organs.
The result was a synthetic mouse embryo model with progenitor or specialized cells with a beating heart, well-folded brain, yolk sac, neural tube, intestinal tract, placenta, and early blood circulation with just eight days of development, almost half of the 20 days of gestation that a mouse requires.
Embryo, starting point to generate organs
As Dr. Hanna, Associate Professor at the Weizmann Institute of Science, has explained, “the embryo is the perfect starting point to generate organs and the best 3D bioprinterand that is the key to being able to create mechanisms that allow stem cells to differentiate from specialized cells in the body or directly form entire organs.”
“This has been very difficult up to now and, to achieve this, it has been key to unlocking the coding self-organizing potential of stem cells,” he added.
To do this, as a starting point, they built on previous advances in their lab, such as reprogramming stem cells and returning them to their earliest stage.
In addition, they had the effectiveness of a device that served as a uterus forto culture mouse embryos (natural, in this previous research) by means of a nutrient solution inside continuously moving vessels, simulating the way nutrients are delivered by blood flow to the placenta and strictly controlling oxygen exchange and atmospheric pressure.
In the new study, the team set out to grow a synthetic embryo model solely from mouse stem cells that had been grown for years in a Petri dish, bypassing the need to start with a fertilized egg.
Division into three groups
Before placing these cells in the exutero device, they divided them into 3 groups: one group that was left as is, and another two that were pretreated to give rise to extraembryonic tissues. When mixed in the device, 0.5 percent formed spheres that developed into an embryo-like structure. Subsequently, the researchers were able to observe the placenta and yolk sacs forming outside the embryos and the synthetic model developing as in a natural embryo.
“When compared to natural mouse embryos, the synthetic models showed a 95 percent similarity in both the shape of the internal structures as well as in the patterns of gene expression of the different cell types. The organs observed in the models gave every indication of being functional,” says Dr. Hanna.
A range of possibilities
The most realistic long-term goal is to study how stem cells form various organs in the developing embryo to open up new therapeutic horizons in organ transplantation. This could raise the possibility that tissues and organs could one day be grown using synthetic embryo models.
But in order to have the possibility of developing cells for therapeutic purposes, it is necessary to understand their reprogramming and differentiation mechanisms, 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’.
In addition, this project could contribute to simplifying the ethical debate on experimenting with natural embryos, in addition to reducing laboratory tests on animals.
To a large extent, the technical and ethical problems posed by the use of natural embryos in research and biotechnology could be circumvented. Even in the case of mice, certain experiments are currently unfeasible because they would require thousands of embryoswhile access to models derived from mouse embryonic cells, which grow in laboratory incubators by the millions, is virtually unlimited.
The next challenge is understanding how stem cells know what to do: how they self-assemble into organs and find their way to their assigned places within an embryo. And because this system, unlike a uterus, is transparent, it may prove useful for modeling birth defects and implantation of human embryos.
“Instead of developing a separate protocol to grow each type of cell -for example, those of the kidney or the liver-, perhaps one day we can create a synthetic model similar to the embryo and then isolate the cells that we need. We will not have to dictate to emerging bodies how they should develop. The embryo itself does it better,” concludes Dr. Hanna.
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