Multicellular 3D models to study myocardial ischemia-reperfusion injury

Front Cell Dev Biol. 2024 Nov 15:12:1494911. doi: 10.3389/fcell.2024.1494911. eCollection 2024.

Abstract

Coronary heart disease is a major global health threat, with acute myocardial ischemia-reperfusion injury (IRI) being a major contributor to myocardial damage following an ischemic event. IRI occurs when blood flow to ischemic tissues is restored and exacerbates the cellular damage caused by ischemia/hypoxia. Although animal studies investigating IRI have provided valuable insights, their translation into clinical outcomes has been limited, and translation into medical practice remains cumbersome. Recent advancements in engineered three-dimensional human in vitro models could offer a promising avenue to bridge the "therapeutic valley of death" from bench to bedside, enhancing the understanding of IRI pathology. This review summarizes the current state-of-the-art cardiovascular 3D models, including spheroids, organoids, engineered cardiac microtissues, and organ-on-a-chip systems. We provide an overview of their advantages and limitations in the context of IRI, with a particular emphasis on the crucial roles of cell-cell communication and the multi-omics approaches to enhance our understanding of the pathophysiological processes involved in IRI and its treatment. Finally, we discuss currently available multicellular human 3D models of IRI.

Keywords: 3D models; cardiac tissue; cardiomyocyte; endothelial cell; ischemia–reperfusion; organoids.

Publication types

  • Review

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. JK and MCP were supported by a Top consortia for Knowledge and Innovation (TKI) - Public Private Partnership (PPP) Grant.