During the past decades, stem cell-based therapy has acquired a encouraging role in regenerative medicine. improved regenerative capacity. Genetic and nongenetic modifications, chemical and physical preconditioning, and the application of biomaterials were found to significantly enhance the regenerative capacity of transplanted stem cells. In this review, we will give an overview of the recent developments in stem cell engineering with the goal to facilitate stem cell delivery and to promote their cardiac regenerative activity. 1. Cardiovascular Disorders in the Modern World Cardiovascular diseases (CVDs) are the major cause of mortality and disability worldwide. In the United States alone, approximately one million myocardial infarctions (MI) occur yearly, and many of these patients develop heart failure, which is currently diagnosed in five million patients [1C3]. Due to the high number of patients and high-cost treatment, CVDs also represent a serious financial burden order AUY922 [1, 4]. CVDs include various disorders affecting the heart and vessels: coronary heart disease, cerebrovascular disease, peripheral arterial disease, rheumatic heart disease, congenital heart disease, deep vein thrombosis, and pulmonary embolism. Among these, the most frequent cases of tissue ischemia are associated with coronary heart disease, stroke, and peripheral arterial disease, which together account for more than half of all CVDs . Until recently, the heart was suggested to be a terminally differentiated organ incapable of regeneration. Vegfa However, the most recent findings have confirmed that at order AUY922 the age of 20 the renewal rate for cardiomyocytes reaches 1%, whereas at 70 it decreases down to 0.4% per year [2, 5]. At the same time, even without diagnosed heart disease, cardiac overload or the aging process are associated with significant loss of cardiomyocytesup to 20 million yearly (to compare, the left ventricle contains 2C4 billion cardiomyocytes). Furthermore, an acute event such as MI causes loss of billions of cells, reaching 25% of the total heart mass . Since cardiomyocytes are endogenously regenerated in a very limited degree, compensation of this cell loss is usually achieved by formation of fibrotic scar tissue that does impair heart contractility . 2. Cell Therapy for Cardiovascular RegenerationAn Alternate Treatment Approach Currently, you will find no efficient pharmaceutical or surgical strategies for the prevention of ischemia-mediated damage and for full regeneration of the hurt heart tissue . Besides cardiac resynchronization, angioplasty, or ventricular aid devices, several drugs are applied for the management of hypertension or dyslipidemia and for the control of metabolic symptoms . In particular, all current pharmacological treatments applied in heart failure are principally palliative: they are helpful in improving the quality of life but are not able to change the course of disease. In this regard, the only curative option is usually heart transplantation. Similarly, in MI treatment, even the most successful developments in surgery are restricted to an improvement of blood supply through manipulation of large vessels . At the same time, one of the key mechanisms for inoperable heart conditions is usually microangiopathy, where the lack of microcirculation is causing ischemia. Thus, current medical developments are not able to significantly switch the course of MI too. To order AUY922 conclude, the current status of therapy for CVDs is usually insufficient and development of safe and efficient alternate treatments is necessary. Gene or stem cell therapy and their combination are the major encouraging strategies thereof. In contrast to currently applied treatments, stem cells have the potential to stimulate and support endogenous mechanisms of cardiac repair and thus provide the basis for full regeneration of damaged heart tissue. 2.1. Cell Types Currently Applied Two main categories of stem cells.