Korean Circ J.  2023 Jun;53(6):367-386. 10.4070/kcj.2023.0098.

Are There Hopeful Therapeutic Strategies to Regenerate the Infarcted Hearts?

• Oh GC
• Choi YJ
• Park BW
• Ban K
• Park HJ

• KMID: 2543050
• DOI: http://doi.org/10.4070/kcj.2023.0098

Abstract

Ischemic heart disease remains the primary cause of morbidity and mortality worldwide. Despite significant advancements in pharmacological and revascularization techniques in the late 20th century, heart failure prevalence after myocardial infarction has gradually increased over the last 2 decades. After ischemic injury, pathological remodeling results in cardiomyocytes (CMs) loss and fibrosis, which leads to impaired heart function. Unfortunately, there are no clinical therapies to regenerate CMs to date, and the adult heart’s limited turnover rate of CMs hinders its ability to self-regenerate. In this review, we present novel therapeutic strategies to regenerate injured myocardium, including (1) reconstruction of cardiac niche microenvironment, (2) recruitment of functional CMs by promoting their proliferation or differentiation, and (3) organizing 3-dimensional tissue construct beyond the CMs. Additionally, we highlight recent mechanistic insights that govern these strategies and identify current challenges in translating these approaches to human patients.

Keyword

Ischemic heart disease; Cardiac niches; Cardiomyocytes; Heart development; Cardiac regeneration

Figure

• 

  Figure 1 Angiogenesis and immune modulation.CPC = cardiac progenitor cell; ECM = extracellular matrix; EPC = endothelial progenitor cell; FGF = fibroblast growth factor; G-CSF = granulocyte-colony stimulating factor; HGF = hepatocyte growth factor; HPC = hematopoietic progenitor cell; MSC = mesenchymal stem cell; MΦ = macrophage; VEFG-A = vascular endothelial growth factor-A.

• 

  Figure 2 Recruitment of functional cardiomyocytes.CM = cardiomyocyte; HAND2 = Heart And Neural Crest Derivatives Expressed 2; hESC = human embryonic stem cell; hiPSC = human induced pluripotent stem cell; hPSC-CM = human pluripotent stem cell-derived cardiomyocyte; NRG1 = neuregulin 1.

• 

  Figure 3 Exploring 3D structures beyond cardiomyocytes.hESC = human embryonic stem cell; hiPSC = human induced pluripotent stem cell, hPSC-CM = human pluripotent stem cell-derived cardiomyocyte; hPSC-EC = human pluripotent stem cell-derived endothelial cell; hPSC-CF = human pluripotent stem cell-derived cardiac fibroblast; PLGA = polylactic-co-glycolic acid.

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