Engineered Human Cardiac Microtissues: The State-of-the-(He)art

Abstract

Due to the integration of recent advances in stem cell biology, materials science, and engineering, the field of cardiac tissue engineering has been rapidly progressing toward developing more accurate functional 3D cardiac microtissues from human cell sources. These engineered tissues enable screening of cardiotoxic drugs, disease modeling (eg, by using cells from specific genetic backgrounds or modifying environmental conditions) and can serve as novel drug development platforms. This concise review presents the most recent advances and improvements in cardiac tissue formation, including cardiomyocyte maturation and disease modeling.

Modeling Heart Diseases on a Chip: Advantages and Future Opportunities

“…[18][19][20] We would like to direct readers to who wish to gain more familiarity with principles of HOC, designs and fabrication approaches or who would like more details to published reviews that cover these particular aspects. 11,15,17,21 Different heart diseases can be modeled using HOC platforms through diverse approaches, such as modification of cell composition, 22 addition of soluble factors, 18,23 or using cells from specific genetic backgrounds [24][25][26][27] (Figure 3). As mentioned previously, HOC disease models offer distinct advantages over monolayer and animal models, with a comparison of different approaches summarized in the Table 1.…”

“…8,9 To address the limitations of traditional cardiac disease models, 2 different yet overlapping tissue engineering approaches have been employed in the generation of cardiac microtissues: spheroid/organoid or hearton-a-chip (HOC) tissues. [10][11][12] Spheroid or organoidstyle cardiac tissue engineering approaches rely on the self-assembly of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) and other cell types into spherical structures. 13,14 These spheroids offer advantages over traditional monolayer approaches such as displaying a more native architecture and enabling improved cell-cell communication between CMs and other cell types while using fewer cells than other tissue engineering approaches.…”

Accelerating cardiovascular research: recent advances in translational 2D and 3D heart models

“…Importantly, this tissue showed the ability to pump fluid, which resembled cardiac physiology, more specifically the Frank-Starling mechanism which describes the relationship between stroke volume and end-diastolic volume in the heart. 87,88 Collectively, engineered cardiac microtissues display a great opportunity in the field of cardiac regenerative/replacement approaches. However, for clinical applications, the transplantation strategies need to be improved in several ways.…”

“…To model the native ventricle, hiPSC‐derived ventricular CMs were engineered into a human ventricle‐like cardiac organoid chamber. Importantly, this tissue showed the ability to pump fluid, which resembled cardiac physiology, more specifically the Frank–Starling mechanism which describes the relationship between stroke volume and end‐diastolic volume in the heart 87,88 …”

Dynamic and static biomechanical traits of cardiac fibrosis

“…At present, a variety of “cardiac tissue chips” have been developed to simulate and manipulate dynamic mechanical microenvironment of cardiac tissue at the micro-scale by combining with microfabrication or microfluidic technology, providing real-time insights into fibrosis events. Moreover, cardiac tissue chips can offer an extraordinary way to precisely manage different microenvironment signals (e.g., abnormal stretch or fluid shear stress) to construct biomimetic 3D in vitro cardiac fibrosis models ( Duval et al, 2017 ; Soon et al, 2021 ). For example, Zhao et al (2019) described a scalable tissue-cultivation platform that is cell source agnostic and enables drug testing under electrical pacing ( Figure 3C ).…”