Regenerative potential of fetal-like human cardiac tissue

JE Hudson

Centre for Cardiac and Vascular Biology, School of Biomedical Sciences, The University of Queensland

Over the past few years, advances in pluripotent stem cell culture and directed differentiation protocols have now made it possible to create human tissue organoids. Very recently cerebral, intestinal, stomach, lung and neural networks have all been reported and have the ability to self-organise to recapitulate their tissues of origin in both geometry and function, provided the correct environment is provided. This represents a revolution in tissue culture as the modelling of development and/or disease. This is because even minor alterations in protein functions or environment can have profound effects on tissue function. I will present how we are now able to use human pluripotent stem cells to produce large numbers of human cardiomyocytes as a research tool or potentially for regenerative applications. In traditional 2D cultures these human cardiomyocytes have been proven to recapitulate some of the properties of native heart tissue, however, many properties closely resemble embryonic-like cardiomyocytes. In order to enhance the functionality of the human pluripotent stem cell cardiomyocytes we have used tissue engineering to produce human cardiac organoids. These organoids have progresses to a fetal-like stage in terms of maturation and we can also record functional properties in these tissues (eg. electrophysiology, calcium transients, force measurements). It has been well documented now that neonatal mice have a regenerative potential which is rapidly lost during the first week of postnatal life. There have been documented case studies in newborn humans where there has been recovery of function following myocardial infarction, however, cardiac regeneration has not been formally tested. Therefore, we determined the regenerative response in fetal-like human cardiac organoids to determine whether humans also exhibit a transient regeneration capacity in the heart.