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Growing organs in the laboratory were once science fiction. But now, methods like stem cell biology and tissue engineering have turned that fiction into reality with the advent of organoids.
Organoids are small laboratory-grown tissues and organs that are anatomically correct and physiologically functional.
Recently, Matthias Lütolf’s laboratory at EPFL’s School of Life Sciences successfully produced a mouse heart organoid in its early embryonic stages. Scientists have grown organoids from mouse embryonic stem cells that, under the right conditions, can self-organize into structures that “mimic aspects of the architecture, cellular composition and function of tissues found in real organs.
Inserted into cell cultures under specific conditions, embryonic stem cells from a three-dimensional aggregate called “gastruloid”, which can follow the developmental stages of the mouse embryo.
The idea of this study was that the mouse gastruloid could be used to mimic the early stages of heart development in the embryo. This is a new use for organoids, which are commonly developed to mimic adult tissues and organs.
Furthermore, there are three characteristics of mouse gastruloids that make them a suitable model for mimicking embryonic development: they establish a body plan like real embryos. They show similar gene expression patterns. And when it comes to the heart, which is the first organ to form and function in the embryo, the mouse gastruloid also preserves important tissue-to-tissue interactions needed to grow one.
Thanks to this, the scientists exposed mouse embryonic stem cells to a “cocktail” of three factors known to promote heart growth. After 168 hours, subsequent gastruloids provided indications for early cardiac development: they expressed several genes that regulate cardiovascular development in the embryo. They even generated what looked like a vascular network.
Importantly, the scientists found that gastruloids developed what they call an “anterior heart crescent-like domain.” This structure produced pulsating heart tissue, similar to the embryonic heart. Like the muscle cells of the embryonic heart, the beating compartment was also sensitive to calcium ions.
Giuliana Rossi, postdoctoral researcher at Lütolf’s laboratory, said: “By opening a whole new dimension to organoids, groundbreaking work shows that they can also be used to mimic the stages of embryonic development. One of the advantages of embryonic organoids is that, through the co-development of multiple tissues, they preserve the crucial interactions that are necessary for embryonic organogenesis. “
“Emerging cardiac cells are thus exposed to a context similar to what they encounter in the embryo.”
The study was conducted in collaboration with Viventis Microscopy, EPFL Bioimaging and Optics Platform, Institut de Biologie du Développement de Marseille, Johns Hopkins University School of Medicine, EPFL Institute of Chemical Sciences and Engineering.
Journal reference:
- Giuliana Rossi, Nicolas Broguiere, Matthew Miyamoto, Andrea Boni, Romain Guiet, Mehmet Girgin, Robert G. Kelly, Chulan Kwon, Matthias P. Lutolf. Capturing cardiogenesis in gastruloids. Cell Stem Cell, 10 November 2020 DOI: 10.1016 / j.stem.2020.10.013
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