Cardiac Organoids and Gastruloids to Study Physio-Pathological Heart Development.

Marisa E Jaconi,Michel Puceat

doi:10.3390/jcdd8120178

Marisa E Jaconi, Michel Puceat

Open Access

https://doi.org/10.3390/jcdd8120178

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Abstract

Ethical issues restrict research on human embryos, therefore calling for in vitro models to study human embryonic development including the formation of the first functional organ, the heart. For the last five years, two major models have been under development, namely the human gastruloids and the cardiac organoids. While the first one mainly recapitulates the gastrulation and is still limited to investigate cardiac development, the second one is becoming more and more helpful to mimic a functional beating heart. The review reports and discusses seminal works in the fields of human gastruloids and cardiac organoids. It further describes technologies which improve the formation of cardiac organoids. Finally, we propose some lines of research towards the building of beating mini-hearts in vitro for more relevant functional studies.

Highlights

Introduction to Study PhysioPathological HeartFollowing fertilization, the human embryo emerges through complex coordinated and time-controlled molecular and morphogenetic events
When the embryo reaches the stage of gastrula, cells have to take major phenotypic decisions in a space- and time-dependent manner to form the three germ layers and later the right organs at the right place [1]
A recent pionneering study [21] reported an in vitro model for embryo aneuploidy, a situation associated with impaired in vitro fertilisation due to chromosolal instability. They treated gastruloids generated from human embryonic stem (hES) cells on micropatterned circular surfaces with reversine, a small molecule inhibitor of monopolar spindle 1 kinase

Summary

Introduction to Study Physio-Pathological Heart

The human embryo emerges through complex coordinated and time-controlled molecular and morphogenetic events. The most recent studies using mammalian embryos and in vitro pluripotent stem cells (PSC) support a role for the crosstalk between tissue shape and cell fate as a determinant of human embryogenesis [1]. Gastrulation is the most important embryonic event in the life of an organism [4] During this process, cells exhibit important changes in shape while differentiating into specific cell fates. It has become challenging to faithfully recapitulate in vitro the complex native environment and in turn different morphogenetic events that temporally shape the human embryo. The heart forms from the lateral plate mesodermal cells that organize during gastrulation. One-week post-fertilization, post-fertilization, cardiogenic move at at the embryonic cardiogenic mesodermal mesodermal cells cells move the cranial border to form a crescent.

Human Gastruloids to Model Birth of Cardiac Progenitors and Diseases

Human Organoids to Model Cardiac Tissue and Diseases

Cardiac Organoids

Sound-Induced Morphogenesis: A Step Forward in Cardiac Tissue Engineering?

Conclusions and Perspectives