Cardiac Tissue Engineering: Inclusion of Non-cardiomyocytes for Enhanced Features.

Sadek Munawar,Irene C Turnbull

doi:10.3389/fcell.2021.653127

Abstract

Engineered cardiac tissues (ECTs) are 3D physiological models of the heart that are created and studied for their potential role in developing therapies of cardiovascular diseases and testing cardio toxicity of drugs. Recreating the microenvironment of the native myocardium in vitro mainly involves the use of cardiomyocytes. However, ECTs with only cardiomyocytes (CM-only) often perform poorly and are less similar to the native myocardium compared to ECTs constructed from co-culture of cardiomyocytes and nonmyocytes. One important goal of co-culture tissues is to mimic the native heart’s cellular composition, which can result in better tissue function and maturity. In this review, we investigate the role of nonmyocytes in ECTs and discuss the mechanisms behind the contributions of nonmyocytes in enhancement of ECT features.

Highlights

Cardiovascular disease is the leading cause of death in the United States (Benjamin et al, 2019)
The heterogeneity of results points to the need to further investigate cardiac cell–cell interactions to achieve the ideal ECT of multicellular composition that reliably mimics the native myocardium
Investigating different cell compositions will allow identification of the ratio needed to yield ECTs with optimal structure and function. These cell mixtures could be tested in the development of bioinks for 3D printing

Summary

INTRODUCTION

Cardiovascular disease is the leading cause of death in the United States (Benjamin et al, 2019). Stevens et al (2009) created tissues from co-culture of hESC-CMs with human umbilical vein endothelial cells (HUVECs) and mouse embryonic fibroblasts (MEFs) that developed significantly more vessel structures and collagen content (Figures 1D–F) than CMonly tissues; these tri-culture tissues displayed passive mechanical properties with greater resemblance to native myocardium (neonatal pig and rat cardiac tissue), and transplantation onto naïve rat heart resulted in improved CM survival and larger graft formation. Two methods of engineered tissue culture, (1) concurrent co-culture and (2) CMs seeded on pre-culture of nonmyocytes (pre-culture or pre-treatment), with similar cellular composition result in strikingly different ECTs. Compared to concurrent co-culture, the pre-culture group exhibited better contractile properties, along with enhancement of other features, in tissues with FBs (Radisic et al, 2008), ECs (Narmoneva et al, 2004), or both (Iyer et al, 2009). The favorable environment created by the pre-culture of nonmyocytes through ECM deposition likely improved tissue function in these studies

SUMMARY AND PERSPECTIVES

Findings

CONCLUSION