After specific screening, amniotic fluid stem cells were amplified in vitro for use directly or c. advancement in cardiac regeneration therapy. However, pluripotent stem cell-derived cardiomyocytes have certain drawbacks, such as the risk of arrhythmia and immune incompatibility. Thus, amniotic fluid stem cells (AFSCs), a relatively novel source of stem cells, have been exploited for their ability of pluripotent differentiation. In addition, since AFSCs are weakly positive for the major histocompatibility class II molecules, they may have high immune tolerance. In summary, the possibility of development of cardiomyocytes from AFSCs, as well as their transplantation in host cells to produce mechanical contraction, has been discussed. Thus, this review article highlights the progress of AFSC therapy and its application in the treatment of heart diseases in recent years. Keywords: amniotic fluid stem cells, pluripotent stem cells, stem cell therapy, cardiovascular diseases, regenerative therapy 1. Introduction Despite huge improvements in medical therapy nowadays, cardiovascular diseases are still the leading cause of mortality worldwide. Moreover, there is an upward pattern in mortality every year. Although novel pharmacological therapeutics and surgical or percutaneous transluminal intervention have been developed in the recent years, however, the prognosis of terminal stage heart failure or severe ischemic heart Ethacridine lactate disease is usually worse than many malignancies . It could be because these therapies cannot lead to cardiac regeneration. The heart is composed of cardiomyocytes that possess varying regenerative abilities at different stages of development in mammals. During the fetal period, the cardiomyocytes undergo a complete cell cycle, but they drop their ability to divide within a few days after birth. The cardiomyocytes of adult mammals are terminally differentiated cells with a rate of regeneration of only less than 1% per year . Ethacridine lactate When the adult heart is usually hurt, it enters an incomplete cell cycle but not total cell division, resulting in hypertrophy of the cardiomyocytes. If necrosis of the myocardium occurs, the cardiomyocytes drop their intrinsic regenerative ability, leading to myocardial fibrosis, poor cardiac contraction, and poor prognosis in patients with ischemic heart disease [2,3]. Thus, the compensatory effect increases the burden Ethacridine lactate around the heart, posing a high risk of its failure . The most effective treatment for heart failure is usually heart transplantation, but due to a shortage in the supply of donor hearts, only a few patients undergo this treatment. Therefore, use of stem cells to replace the necrotic cardiomyocytes is usually gaining momentum in the research area of heart regeneration. 2. Advantages and Limitations of Different Types of Stem Cells in Cardiac Regeneration There are different types of stem cells involved in the development process of organisms. Based on differentiation ability, stem cells are categorized as totipotent, pluripotent, multipotent, and unipotent. Among these groups, embryonic stem cells (ESCs) are pluripotent in nature, which can be induced to differentiate into almost every cell type; however, their application is limited due to ethical concerns . Compared with ESCs, multipotent stem cells are located at multiple sites, such as adipose tissue, connective tissue, bone marrow, etc., and most of them are classified as mesenchymal stem cells (MSC). MSCs are considered to have immune privileges in regenerative therapy. They secrete many biologically active molecules, including cytokines, growth factors, and chemokines and regulate Ethacridine lactate the activity of immune cells such as B cells, T cells, dendritic cells (DC), natural killer (NK) cells, neutrophils, and macrophages through autocrine and paracrine effects [5,6]. MSC are also not restricted by ethics and are found in many cell types, since they can differentiate into some specific types of cells. Moreover, most MSCs have FANCE a limited ability of cardiomyocyte differentiation [6,7,8]. In addition, using MSC as a material of myocardial repair has low efficacy. After using MSC derived cardiomyocyte after myocardial infarctions in animal models, the function of the left ventricular still has not been significantly improved.