Abstract
Medical research in the recent years has achieved significant progress due to the increasing prominence of organoid technology. Various developed tissue organoids bridge the limitations of conventional 2D cell culture and animal models by recapitulating in vivo cellular complexity. Current 3D cardiac organoid cultures have shown their utility in modelling key developmental hallmarks of heart organogenesis, but the complexity of the organ demands a more versatile model that can investigate more fundamental parameters, such as structure, organization and compartmentalization of a functioning heart. This review will cover the prominence of cardiac organoids in recent research, unpack current in vitro 3D models of the developing heart and look into the prospect of developing physiologically appropriate cardiac organoids with translational applicability. In addition, we discuss some of the limitations of existing cardiac organoid models in modelling embryonic development of the heart and manifestation of cardiac diseases.
Highlights
Congenital heart defects (CHD) affects approximately 0.4–5% of live births worldwide, making it the most common form of congenital disease (Kloesel et al, 2016)
The advent of pluripotent stem cells (PSCs), of both embryonic stem cells (ESC) and induced pluripotent stem cell origins differentiated into various cell lineages, provides novel insights to embryonic development and regenerative biology (Murry and Keller 2008; Zhu and Huangfu 2013; Tabar and Studer 2014)
These induced pluripotent stem cell (iPSC) enabled advancements in cardiac embryogenesis research and helped uncover the critical roles morphogens such as BMP, Wnt, FGFs, TBX5 and GATA4 play in gastrulation and mesodermal patterning in vivo (Andersen et al, 2018). These finding have enabled the understanding of how diverse lineages and anatomical structure of Insights to Heart Development the heart arise from the specification of two cardiac progenitor origins, the first heart field (FHF) and the second heart field (SHF)
Summary
Congenital heart defects (CHD) affects approximately 0.4–5% of live births worldwide, making it the most common form of congenital disease (Kloesel et al, 2016). Human iPSCs offer a unique platform to study genetic mutations and developmental pathways associated with CHD These iPSCs enabled advancements in cardiac embryogenesis research and helped uncover the critical roles morphogens such as BMP, Wnt, FGFs, TBX5 and GATA4 play in gastrulation and mesodermal patterning in vivo (Andersen et al, 2018). These finding have enabled the understanding of how diverse lineages and anatomical structure of. This review will focus on some key aspects of embryonic development of the heart, using 2D iPSC derived cardiomyocytes and 3D cardiac organoid models that serve to enhance our understanding of the genetic basis of development and pathophysiology of heart diseases. We discuss some of the key limitations of current in vitro models
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