Self-organising heart organoids using human pluripotent stem cells have been developed by researchers from the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA).
These heart organoids the size of a sesame seed, known as cardioids, developed structures with a cavity resembling the structures that go on to form the atrium and ventricles of the human heart. The chamber-like structures could also beat after eight days of development and they contained an inner layer similar to the endothelial lining present in a developing heart that later contributes to the development of heart vasculature.
'Cardioids are a major milestone. Our guiding principle is that for an in vitro tissue to be fully physiological, it also needs to undergo organogenesis. We were able to achieve this, using the developmental principles of self-organisation – which makes it such an exciting discovery,' said Dr Sasha Mendjan, group leader at IMBA, Austria, who is a co-author of this research.
In their paper published in the journal Cell, the scientists report how they were able to guide the development of human stem cells into cardioids by establishing conditions that mimic the embryonic environment during early embryonic development. They aimed to produce the three layers of tissue observed in the human heart chamber and did this by putting the stem cells into concentrations of growth-promoting nutrients to encourage them to develop in the order they would in an embryo.
'Amazingly, this led to self-organisation of a heart chamber-like structure that was beating. For the first time, we could observe something like this in a dish. It is a simple, robust and scalable model, and does not require addition of exogenous extracellular matrix like many other organoid models,' said Dr Mendjan.
Hofbauer and colleagues were also able to generate cardioids that mimicked a condition observed in children known as Hypoplastic Left Heart Syndrome, through the modification of transcription factors associated with this syndrome. They also investigated the impact of injuring the cardioids through freezing which is a technique that mimics heart attacks in these self-organised heart organoids. This resulted in the accumulation of extracellular matrix proteins which is a hallmark of heart disease and regeneration.
Cardioids hold great potential as a tool for studying human heart diseases and testing potential therapeutics. Further studies will be conducted by the team in efforts to generate organoids with all four chambers of the human heart.