Abstract
Organoids are tiny, self-organized, three-dimensional tissue cultures that are derived from the differentiation of stem cells. The growing interest in the use of organoids arises from their ability to mimic the biology and physiology of specific tissue structures in vitro. Organoids indeed represent promising systems for the in vitro modeling of tissue morphogenesis and organogenesis, regenerative medicine and tissue engineering, drug therapy testing, toxicology screening, and disease modeling. Although 2D cell cultures have been used for more than 50 years, even for their simplicity and low-cost maintenance, recent years have witnessed a steep rise in the availability of organoid model systems. Exploiting the ability of cells to re-aggregate and reconstruct the original architecture of an organ makes it possible to overcome many limitations of 2D cell culture systems. In vitro replication of the cellular micro-environment of a specific tissue leads to reproducing the molecular, biochemical, and biomechanical mechanisms that directly influence cell behavior and fate within that specific tissue. Lineage-specific self-organizing organoids have now been generated for many organs. Currently, growing cardiac organoid (cardioids) from pluripotent stem cells and cardiac stem/progenitor cells remains an open challenge due to the complexity of the spreading, differentiation, and migration of cardiac muscle and vascular layers. Here, we summarize the evolution of biological model systems from the generation of 2D spheroids to 3D organoids by focusing on the generation of cardioids based on the currently available laboratory technologies and outline their high potential for cardiovascular research.
Highlights
The term “organoid” refers to mini clusters of growing cells able to self-organize in vitro and differentiate into functional cell types, resembling an organ 3D structure and function
We thoroughly assess the current methodologies used to generate cardiac spheroids and 3D-cell structures derived from stem cells, and highlight the potential of cardiac organoids (“cardioids”) as a model system for the understanding of heart development and for the study of human cardiac regeneration in a dish
In 1960, Weiss and Taylor conducted the same experiments with different organs from chicken embryos [8], and shortly later, Pierce and Verney described the differentiation of embryoid bodies (EBs) in vitro [9] (Figure 1)
Summary
The term “organoid” refers to mini clusters of growing cells able to self-organize in vitro and differentiate into functional cell types, resembling an organ 3D structure and function. Organoids are stem cell-derived and self-organizing 3D cultures that phenocopy cell-type composition, architecture, and, to a certain extent, functionality of different tissues [1]. Organoids are similar to primary tissue in their composition and architecture, harboring small populations of genomically stable, self-renewing stem cells that give rise to fully differentiated progeny comprising all major cell lineages. The study of organoid formation can provide valuable information about the mechanisms underlying development and organ regeneration, underscoring their value for basic biological research in addition to their potential application in drug testing and molecular medicine. We thoroughly assess the current methodologies used to generate cardiac spheroids and 3D-cell structures derived from stem cells, and highlight the potential of cardiac organoids (“cardioids”) as a model system for the understanding of heart development and for the study of human cardiac regeneration in a dish. We argue that cardioids are ideal human preclinical models, useful to simulate pathological processes as well as to test drug toxicity, highlighting their current limitations that remain to be addressed
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