Cardiac Organoids to Model and Heal Heart Failure and Cardiomyopathies

Abstract

Cardiac tissue engineering aims at creating contractile structures that can optimally reproduce the features of human cardiac tissue. These constructs are becoming valuable tools to model some of the cardiac functions, to set preclinical platforms for drug testing, or to alternatively be used as therapies for cardiac repair approaches. Most of the recent developments in cardiac tissue engineering have been made possible by important advances regarding the efficient generation of cardiac cells from pluripotent stem cells and the use of novel biomaterials and microfabrication methods. Different combinations of cells, biomaterials, scaffolds, and geometries are however possible, which results in different types of structures with gradual complexities and abilities to mimic the native cardiac tissue. Here, we intend to cover key aspects of tissue engineering applied to cardiology and the consequent development of cardiac organoids. This review presents various facets of the construction of human cardiac 3D constructs, from the choice of the components to their patterning, the final geometry of generated tissues, and the subsequent readouts and applications to model and treat cardiac diseases.

A versatile high-throughput assay based on 3D ring-shaped cardiac tissues generated from human induced pluripotent stem cell derived cardiomyocytes

“…The combination of pluripotent stem cells technologies, advanced cardiomyocyte differentiation protocols and microfabrication methods have already resulted in the generation of engineered human cardiac muscle tissue-constructs, with different shapes and that can reproduce some cardiac functions ( Seguret et al (2021) ; Cho et al (2022) ). However, until now, approaching the complex geometry and structure of the human myocardium required complex techniques, which limits the number of tissues produced, thus hampering their application for high-throughput experiments.…”

Chronic Cardiotoxicity Assays Using Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes (hiPSC-CMs)

“…In the most recent year’s studies, there have been significant advances in commercial cardiomyocyte production, 3D assay development [ 76 , 77 , 78 , 79 ] and refinement of CRISPR-Cas9 mediated gene editing [ 80 , 81 , 82 , 83 ] that will help overcome a majority of these current limitations. Further research is warranted to standardize these long-term, high-throughput assay conditions, improving the reproducibility and sensitivity of endpoints to allow for translational therapeutics.…”

Cardiac organoid: multiple construction approaches and potential applications

“…Secondly, 3D bioprinting requires billions of cells to print large tissues because cell loss often occurs when cells are mixed into a bioink. 15,86 Thirdly, existing 3D printing methods cannot print both the external geometry and the internal microstructures of organoids, such as vascularization. Recently, Fang et al solved this problem by printing ventricular models with perfusable vascular networks using microgel-based biphasic (MB) bioinks by shear thinning, self-healing behavior and sequential printing in reversible ink templates (SPIRIT).…”

“…Cardiac cells interact with the vascular system and are surrounded by a 3D ECM network. The ECM is a complex microenvironment containing laminin proteins, fibronectin, interstitial collagen, cytokines, growth factors, proteases, and glycoproteins, 15 which provide anisotropic alignment, biochemical signaling, and mechanical support for cells. Ideally, hCOs should reproduce the morphology, structure, metabolism, and function of the natural cardiac environment, as well as complex microenvironments, in vivo , such as CMs, non-CMs, vasculature, and ECM networks, to study cell–cell and cell–matrix interactions under normal and pathological conditions.…”