In vitro models of the human heart

Abstract

Cardiac congenital disabilities are the most common organ malformations, but we still do not understand how they arise in the human embryo. Moreover, although cardiovascular disease is the most common cause of death globally, the development of new therapies is lagging compared with other fields. One major bottleneck hindering progress is the lack of self-organizing human cardiac models that recapitulate key aspects of human heart development, physiology and disease. Current in vitro cardiac three-dimensional systems are either engineered constructs or spherical aggregates of cardiomyocytes and other cell types. Although tissue engineering enables the modeling of some electro-mechanical properties, it falls short of mimicking heart development, morphogenetic defects and many clinically relevant aspects of cardiomyopathies. Here, we review different approaches and recent efforts to overcome these challenges in the field using a new generation of self-organizing embryonic and cardiac organoids.

Emergence of heart and branchiomeric muscles in cardiopharyngeal mesoderm

“…Indeed, a number of in vitro models of early heart organogenesis have been recently reported. These comprise juxtaposed FHF and SHF lineages as evaluated by fluorescent reporter genes and analysis of endogenous gene expression and reveal a remarkable level of organisation within the developing organoids [92][93][94][95]. Gastruloids have been shown to recapitulate developmental decisions made in the early embryo at the transcriptional level, suggesting that this will be a powerful approach to dissect the regulation of cell fate acquisition in CPM [93].…”

Effect of Extracellular Matrix Stiffness on Candesartan Efficacy in Anti-Fibrosis and Antioxidation

“…An in vitro model of the cardiac mechanical microenvironment, which can mimic the structure and mechanical properties of natural heart tissues, has been widely used in cardiovascular disease research and drug screening [ 31 , 32 ]. PA gels have been used for the construction of in vitro cardiac mechanical microenvironment models due to their suitable biological properties and adjustable stiffness [ 33 ].…”

Stem Cell Studies in Cardiovascular Biology and Medicine: A Possible Key Role of Macrophages

“…This type of system is necessary to maintain cell viability, and for this purpose, technologies using cell sheets [ 40 ], collagen scaffolds including decellarized matrix [ 41 ], and other synthetic polymers have progressed [ 42 ]. Thus, useful models may be established using these technologies and have recently revived ideas of self-organizing embryonic and cardiac organoids mimicking the physiological developmental process of heart generation in the future [ 43 ].…”