PSC: Pluripotent stem cell Sca-1: Stem cell antigen-1. Thus, de novo cardiomyocyte generation from pluripotent stem cells (embryonic or induced) remains the most promising approach for cell-based therapies, provided that the field can overcome limitations such as immune rejection and the induction of arrhythmias. However, recent lineage tracing experiments demonstrate that myocardial regeneration occurs through cardiomyocyte proliferation. Several groups proposed the existence of cardiac stem cells (orange), and their therapeutic potential was tested in animal models and clinical trials. Unfortunately, promising results of bone marrow-derived cells in animal models were not reproduced in clinical trials. Bone marrow-derived cells (purple) include mononuclear cells, mesenchymal stromal cells, and c-kit + hematopoietic stem cells, which can be used in autologous or allogeneic therapies. Skeletal myoblasts (red) were the first cell type used for cell therapies but induced life-threatening arrhythmias due to myocardial uncoupling. In this review, we will discuss the various cell therapies that were applied to treat cardiac diseases, the questionable existence of an endogenous cardiac stem cell (CSC) and their putative cardiac regenerative potential, and, finally, what we envisage as the future in the field which is using cardiomyocytes derived from pluripotent stem cells or their derivatives, such as exosomes and microvesicles (Figure 1).įigure 1 Cell-based therapies for ischemic heart disease.Ĭells can be obtained from several different sources. In the 1990s, the idea to replace the cardiomyocytes lost due to ischemic diseases with an external cell source paved the way for cell therapies for regenerative medicine in cardiology. This represents a significant public health problem, pushing researchers to look for effective alternative treatments. The therapeutic option for heart failure patients is an organ transplant, but the demand is far greater than the avail ability of such organs. Due to the limited cardiac regenerative capacity, the lost cardiomyocytes are replaced by fibrotic scarring, leading to cardiac remodeling and heart failure. However, this neither contributes to the recovery of the function of the damaged tissue nor stops the progression of ischemic disease. Acute interventions can restore blood flow, avoiding the death of more cardiac cells. Despite improvements in the clinical-surgical management of these patients, the main effect of ischemic heart disease - the death of cardiomyocytes - is not reversed. Coronary artery occlusion or reduction of blood flow results in irreversible death of cardiac cells with consequent functional cardiac impairment. Acellular therapies using cell derivatives, such as microvesicles and exosomes, are presented as a promising cell-free therapeutic alternative.Ĭardiovascular diseases represent the world’s leading cause of death, and in this heterogeneous group of diseases, ischemic cardiomyopathies are the most prevalent, accounting for 17.9 million deaths per year. The outcomes of cardiac cell therapies are discussed in three distinct aspects: The search for remuscularization by replacement of lost cells by exogenous adult cells, the endogenous stem cell era, which pursued the isolation of a progenitor with the ability to induce heart repair, and the utilization of pluripotent stem cells as a rich and reliable source of cardiomyocytes. In this review, we will cover more than 30 years of cell therapy in cardio logy, presenting the main milestones and drawbacks in the field and signaling future challenges and perspectives. In this context, cell therapy is an emerging therapeutic alternative to treat cardiovascular diseases by cell administration, aimed at cardiac regeneration and repair. Despite all biomedical efforts, there are no effective treatments that can replace the myocytes lost during an ischemic event or progression of the disease to heart failure. In this heterogeneous group of diseases, ischemic cardiomyopathies are the most devastating and prevalent, estimated to cause 17.9 million deaths per year. Cardiovascular diseases represent the world’s leading cause of death.
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