Building a new strategy for treating heart failure using Induced Pluripotent Stem Cells

Abstract

Although cell therapy using myoblasts, bone marrow cells, or other stem cells appears to improve functional recovery of the failing heart, mainly by cytokine paracrine effects, its effectiveness in severely damaged myocardium is limited, probably because there are too few residual myocytes to promote cytokine-induced angiogenesis. Recently, cardiogenic stem cells, such as c-kit-positive cells, were reported to generate cardiomyogenic lineages, and basic research experiments showed that implanting these cells, which can differentiate into cardiomyocytes, improves heart function. However, this functional recovery may have also mainly depended on cytokine paracrine effects, because the differentiation to cardiomyocytes in vivo was poor. In contrast, while Induced Pluripotent Stem Cell-derived cardiomyocytes have paracrine effects, they also have the potential to supply newly born myocytes that can function synchronously with the recipient myocardium as "mechanically working cells" in severely damaged myocardium. Thus, they could represent a "true" myocardial regeneration therapy that can actually regenerate severely damaged myocardium. In addition, iPS cells, especially disease-specific iPS cells, have other applications in regenerative medicine such as in drug screening. In this report, we present the state of basic research in the field of cardiac iPS cells.

New trends in cellular therapy

“…The first transplant of hESC-derived cardiac progenitors was performed for treatment of severe heart failure treatment by Menasché et al 2015, with no adverse effects over a 3-month follow-up period. Following pre-clinical work confirming the safety and effectiveness of iPSC-derived cardiomyocyte sheets in animal experiments (Miyagawa and Sawa, 2018;Ishida et al, 2019), a team led by Yoshiki Sawa at Osaka University performed a world-first transplant of iPSC-based cellular therapy for heart disease, using HLA-non matched iPSC-derived cardiomyocytes in the form of cardiomyocyte sheets (https://www.bionews.org.uk/page_147579).…”

State-of-the-Art Technology of Model Organisms for Current Human Medicine

“…Since the discovery of transcription factor-induced pluripotent stem (iPS) technology [14,15], regenerative medicine for corneal endothelial cells [16], cardiocytes [17], hepatocytes [18], and drug screening has been established [19]. Remarkably, the present in vitro technology can increase cell sheets or partial tissues, which are far from organs with complex structures formed after natural development and are not induced by embryonal stem (ES) cells in vivo.…”

Comparison of the Simulated Response of Three in Silico Human Stem Cell-Derived Cardiomyocytes Models and in Vitro Data Under 15 Drug Actions

“…Human stem cell-derived cardiomyocytes (hSC-CMs) have emerged as a promising tool for translational research, cardiac repair and drug development (Bezzerides et al, 2017;Miyagawa and Sawa, 2018;de Korte et al, 2020). After the initial hype, it has, however, become widely acknowledged that with current methods and technology hSC-CMs have a fundamental limitation: the cells cannot be fully matured into human ventricular cardiomyocytes (hV-CMs).…”