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There was a time when the idea of growing organs in the laboratory was science fiction stuff. Today, stem cell biology and tissue engineering are turning fiction into reality with the advent of organoids – tiny, lab-grown tissues and organs that are anatomically correct and physiologically functional.
The appeal of organoids is obvious. In essence, they can provide us with on-demand production of tissues and mini-organs for pharmaceutical and medical research, without having to constantly rely on donors. And while that goal may still be a long way off, we are slowly getting closer.
EPFL has been involved in organoid development for some time, with Matthias Lütolf’s lab at the School of Life Sciences leading the charge. This year alone, Lütolf’s group published articles on standardizing organoid growth, 3D printing organoids, and actually producing an organoid-based functional mini-intestine – a revolutionary Nature paper that is leading the way in this field.
Now, Lütolf’s lab has successfully produced a mouse heart organoid in its early embryonic stages. The project was led by Giuliana Rossi, postdoctoral researcher in the Lütolf laboratory, and published in the journal Cell stem cells.
The researchers cultured their organoids from mouse embryonic stem cells, which, 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,” as they stated the researchers in the paper. Embryonic stem cells, placed in cell culture under specific conditions, form a three-dimensional aggregate called “gastruloid”, which can follow the developmental stages of the mouse embryo.
The idea behind this study was that mouse gastruloid can be used to mimic the early stages of heart development in the embryo. This is a rather unexplored use of organoids, which are generally grown to mimic adult tissues and organs. But 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 and 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.
Armed with this, the researchers exposed mouse embryonic stem cells to a “cocktail” of three factors known to promote heart growth. After 168 hours, the resulting gastruloids showed signs of early cardiac development: they expressed several genes that regulate cardiovascular development in the embryo and even generated what appeared to be a vascular network.
More importantly, the researchers found that the gastruloids developed what they call an “anterior heart crescent-shaped domain.” This structure produced pulsating heart tissue, similar to the embryonic heart. And just like the muscle cells of the embryonic heart, the beating compartment was also sensitive to calcium ions.
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,” says Giuliana Rossi. “Emerging cardiac cells are thus exposed to a context similar to what they encounter in the embryo.”
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