Induced Pluripotent Stem Cell-Derived Cardiomyocytes Therapy for Ischemic Heart Disease in Animal Model: A Meta-Analysis

Abstract

Ischemic heart disease (IHD) poses a significant challenge in cardiovascular health, with current treatments showing limited success. Induced pluripotent derived–cardiomyocyte (iPSC-CM) therapy within regenerative medicine offers potential for IHD patients, although its clinical impacts remain uncertain. This study utilizes meta-analysis to assess iPSC-CM outcomes in terms of efficacy and safety in IHD animal model studies. A meta-analysis encompassing PUBMED, ScienceDirect, Web of Science, and the Cochrane Library databases, from inception until October 2023, investigated iPSC therapy effects on cardiac function and safety outcomes. Among 51 eligible studies involving 1012 animals, despite substantial heterogeneity, the iPSC-CM transplantation improved left ventricular ejection fraction (LVEF) by 8.23% (95% CI, 7.15 to 9.32%; p < 0.001) compared to control groups. Additionally, cell-based treatment reduced the left ventricle fibrosis area and showed a tendency to reduce left ventricular end-systolic volume (LVESV) and end-diastolic volume (LVEDV). No significant differences emerged in mortality and arrhythmia risk between iPSC-CM treatment and control groups. In conclusion, this meta-analysis indicates iPSC-CM therapy’s promise as a safe and beneficial intervention for enhancing heart function in IHD. However, due to observed heterogeneity, the efficacy of this treatment must be further explored through large randomized controlled trials based on rigorous research design.

The Role of Stem Cells in the Treatment of Cardiovascular Diseases

“…The authors demonstrated that cellular therapy was associated with a significantly greater LVEF and fractional shortening (FS). However, no significant differences were noted regarding the mortality and presence of ventricular arrhythmias [140].…”

Stem Cell Therapy against Ischemic Heart Disease

“…Another study further showed that a vascular endothelial cell adhesion glycoprotein, cadherin-5, could enhance the differentiation of human iPSCs into sinoatrial node-like pacemaker cells, highlighting the possibility of developing biological pacemakers [172]. Focusing on the experimental results of iPSC-derived cardiomyocyte transplantation for ischemic heart disease, a recent meta-analysis investigating the efficacy and safety of this approach in animal models demonstrated significant improvement in left ventricular ejection fraction and reduction in left ventricle fibrosis area in animals with iPSC-derived cardiomyocyte treatment compared with those without [173]. More importantly, that study demonstrated no significant difference in mortality and arrhythmia risk between the two groups [173].…”

“…Focusing on the experimental results of iPSC-derived cardiomyocyte transplantation for ischemic heart disease, a recent meta-analysis investigating the efficacy and safety of this approach in animal models demonstrated significant improvement in left ventricular ejection fraction and reduction in left ventricle fibrosis area in animals with iPSC-derived cardiomyocyte treatment compared with those without [173]. More importantly, that study demonstrated no significant difference in mortality and arrhythmia risk between the two groups [173]. On the other hand, despite such a strong implication for clinical application, the transplantation of re-engineered cardiomyocytes (so called "second-generation stem cells" [30]) may accompany adverse complications such as tumorigenicity (e.g., teratoma) stemming from vector or cell pluripotency, which is another major concern when harnessing the plasticity of iPSCs in the treatment of ischemic heart disease [167].…”

Current Status of Cardiac Regenerative Therapy Using Induced Pluripotent Stem Cells

“…Meanwhile, in vivo studies have shed new light for research advancements in the utilization of iPSCs in CM regeneration, which can potentially affect human lifespan by way of extension and productivity. Thus, iPSCs became a landmark development in regenerative medicine tested in vivo [ 25 ].…”