Induced pluripotent stem-cell-derived cardiomyocytes: cardiac applications, opportunities, and challenges

Abstract

Chronic diseases are the primary cause of mortality worldwide, accounting for 67% of deaths.One of the major challenges in developing new treatments is the lack of understanding of the exact underlying biological and molecular mechanisms. Chronic cardiovascular diseases are the single most common cause of death worldwide, and sudden deaths due to cardiac arrhythmias account for approximately 50% of all such cases. Traditional genetic screening for genes involved in cardiac disorders is laborious and frequently fails to detect the mutation that explains or causes the disorder. However, when mutations are identified, human induced pluripotent stem cells (hiPSCs) derived from affected patients make it possible to address fundamental research questions directly relevant to human health. As such, hiPSC technology has recently been used to model human diseases and patient-specific hiPSC-derived cardiomyocytes (hiPSC-CMs) thus offer a unique opportunity to investigate potential disease-causing genetic variants in their natural environment. The purpose of this review is to present the current state of knowledge regarding hiPSC-CMs, including their potential, limitations, and challenges and to discuss future prospects.

Ameliorating the Fibrotic Remodeling of the Heart through Direct Cardiac Reprogramming

“…Therefore, developing new strategies of cellular therapies offers more accessible options for a broader group of coronary heart patients and prevents a diseased heart from end-stage failure. Currently, there are five major cellular therapy strategies that have been actively investigated in the past few decades for cardiac regenerative medicine: (1) Transplantation of autologous adult stem cells [2,3,4,5], (2) transplantation of embryonic stem cell (ESC)- or induced pluripotent stem cell (iPSC)-derived CMs [6,7,8], (3) activation of endogenous progenitors [9,10,11,12], (4) cell-cycle reentry of adult CMs [13,14,15,16], and (5) direct cell fate reprogramming [17,18,19,20,21]. Each strategy has shown promising benefits but are also facing different technical challenges [22,23].…”

Cardiac Ion Channel Regulation in Obesity and the Metabolic Syndrome: Relevance to Long QT Syndrome and Atrial Fibrillation

“…Although, to our knowledge, there have been no studies using human stem cells as a research paradigm for studying ion channel remodeling in metabolic diseases. Human stem cells, both embryonic stem cells and induced pluripotent, have been successfully used as models of arrhythmias (Priori et al, 2013; Moreau et al, 2017), suggesting that human stem cells could be a realistic pre-clinical human model for studies focused on arrhythmias underlain by metabolic disorders.…”

Arrhythmogenic cardiomyopathy as a myogenic disease: highlights from cardiomyocytes derived from human induced pluripotent stem cells

“…The human iPSCs (hiPSC) express embryonic factors such as TRA1-60 or SSEA-1, maintain their pluripotency, and demonstrate high self-renewal capabilities. The method has rapidly been expanded and hiPSC can now be obtained from several original tissue types including blood or urine ( Hou et al, 2013 ; Moreau et al, 2017 ; Shi et al, 2017 ).…”

“…The capacity to differentiate hiPSC into spontaneously beating cardiomyocytes was a major advance in the understanding of cardiac pathologies (Burridge et al, 2012). Indeed, hiPSCderived cardiomyocytes (hiPSC-CM) are essential in the study of cardiomyopathies, channelopathies, and molecule screening during drug development or safety studies (Moretti et al, 2010;Sun et al, 2012;Moreau et al, 2017;Sleiman et al, 2020;Poulin et al, 2021;Ait Benichou et al, 2022;Jauvin et al, 2023). Frontiers in Physiology frontiersin.org…”