Combining stem cells in myocardial infarction: The road to superior repair?

Abstract

Myocardial infarction irreversibly destroys millions of cardiomyocytes in the ventricle, making it the leading cause of heart failure worldwide. Over the past two decades , many progenitor and stem cell types were proposed as the ideal candidate to regenerate the heart after injury. The potential of stem cell therapy has been investigated thoroughly in animal and human studies, aiming at cardiac repair by true tissue replacement, by immune modulation, or by the secretion of paracrine factors that stimulate endogenous repair processes. Despite some successful results in animal models, the outcome from clinical trials remains overall disappointing, largely due to the limited stem cell survival and retention after transplantation. Extensive interest was developed regarding the combina-tional use of stem cells and various priming strategies to improve the efficacy of regenerative cell therapy. In this review, we provide a critical discussion of the different stem cell types investigated in preclinical and clinical studies in the field of cardiac repair. Moreover, we give an update on the potential of stem cell combinations as well as preconditioning and explore the future promises of these novel regenerative strategies. Abbreviations: ALDH, aldehyde dehydrogenase; BM, bone marrow; BM-MNC, bone marrow mononuclear cell; CASC, cardiac atrial appendage stem cell; CDC, cardiosphere-derived cell; CPC, cardiac progenitor cell; CVD, cardiovascular disease; Cx43, connexin43; DMOG, dimethyloxalylglycine; EPC, endothelial progenitor cell; EV, extracellular vesicle; hESC, human embryonic stem cell; HIF, hypoxia-inducible factor; HSC, hematopoietic stem cell; iPSC, induced pluripotent stem cell; iPSC-CM, induced pluripotent stem cell-derived cardiomyocyte; Isl-1, islet-1; LAD, left anterior descending; LVEF, left ventricular ejection fraction; LVESV, left ventricular end-systolic volume; MI, myocardial infarction; MSC, mesenchymal stem cell; Sca-1, stem cell antigen-1.