24 May 2021

Cardioids

About 18 million people die annually from cardiovascular diseases, which is the main cause of death worldwide. In children, the most common congenital malformations are heart defects. Currently, the main problem in the study of heart defects and the development of regenerative methods of treatment is the lack of physiological models of the human heart.

Sasha Menjan's research group from the Institute of Molecular Biotechnology of the Austrian Academy of Sciences has created cardioids – self-organizing organoids of the human heart that repeat the architecture of the heart chamber.

Menjan and colleagues held the position that in order for a tissue to be completely physiological in vitro, it must also undergo organogenesis. They were able to achieve this by using the principles of self-organization.

In the process of development, a heart chamber is formed from the mesodermal germ leaf. Researchers in vivo identified mesodermal signals guiding pluripotent stem cells and used them to create a heart model. This led to the self-organization of the tissue in vitro into the cardiac chamber, which is able to contract.

Cardioid is a simple, reliable and scalable model that does not require the addition of an exogenous extracellular matrix, like many other organoids. In addition to the contracting muscle layer (myocardium), the human heart also has an internal endothelial and external epicardial layers; cardioids repeat this three-layer structure, imitating the human heart.

Cardioids.jpg

The group determined which signaling and transcription factors control the formation of the cardioid chamber. Thus, scientists were able to create a model of hypoplasia syndrome of the left heart by disrupting the transcription factor associated with this defect. The researchers also assessed the effect of cryopreservation (injury sustained by freezing to simulate a myocardial infarction) on cardioids. For the first time in vitro, they studied what happens in vivo with this injury: the accumulation of extracellular matrix proteins is an early sign of both regeneration and fibrous heart damage.

Over the past decade, organoid models have revolutionized biomedical research. However, the heart remained the last major internal organ for which there was no such physiological model capable of reproducing the processes of development and reactions to damage. Cardioids have incredible potential for studying human congenital heart defects. Since the system is physiological and scalable, it opens up opportunities for the development of new drugs and the development of regenerative medicine.

Article by P.Hofbauer et al. Cardioids reveal self-organizing principles of human cardiogenesis published in the journal Cell.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on IMBA materials: Cardioids -- heartbeat, heartbreak and recovery in a dish.

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