Researchers at the Austrian Academy of Sciences have developed the most realistic cardiac organoids to date. The tiny structures self-organize from pluripotent stem cells to form a hollow chamber that can beat. The method to create the ‘cardioids’ involves stimulating a variety of signaling pathways in stem cells and does not rely on conventional tissue engineering techniques, which typically employ a scaffold material as a basis for such structures. Consequently, the resulting tissue growth mimics the developmental process in humans. The researchers hope that the organoids will provide more valuable data about heart disease and treatment.
Organoids are hugely valuable in modeling disease and testing treatments. However, in some respects this technology is still in its infancy. Researchers are still refining techniques to create and use organoids in medical research. Many groups adopt a classic tissue engineering approach when assembling organoids, which involves combining cells and a biomaterial scaffold. However, this is a little crude when compared with how organs develop in humans, which typically involves self-organization of cells.
“Self-organization is how nature makes snowflake crystals or birds behave in a flock. This is difficult to engineer because there seems to be no plan, but still something very ordered and robust comes out,” said Sasha Mendjan, a researcher involved in the study. “The self-organization of organs is much more dynamic, and a lot is going on that we do not understand. We think that this ‘hidden magic’ of development, the stuff we do not yet know about, is the reason why currently diseases are not modeled very well.”
Mendjan and his colleagues adopted a different approach, and instead of biomaterials, they activated all the known signaling pathways involved in cardiac differentiation and development in human pluripotent stem cells. There are six known signaling pathways, and the team activated them in a particular sequence. This stimulated the cells to self-organize and grow into a hollow chamber with different layers that demonstrated a beating motion, just like the developing heart.
“It’s not that we are using something different than other researchers, but we are just using all of the signals known,” said Mendjan. “[Other researchers] thought, ‘Okay, they’re not really necessary in vitro.’ But it turns out all these pathways are necessary. They are important to make the cells self-organize into an organ.”
Study in journal Cell: Cardioids reveal self-organizing principles of human cardiogenesis