# Cell Therapy in the Treatment of Coronary Heart Disease
## 1 Introduction  
Coronary heart disease (CHD), also known as ischemic heart disease, is a common condition that is the leading cause of mortality and disability in adults [1, 2]. Myocardial ischemia occurs when the oxygen demand of the myocardial tissue exceeds the ability of the coronary arteries to deliver it due to a primary reduction in coronary blood flow and/or a reduction in coronary reserve. The term \"myocardial infarction\" (MI) is used when there is evidence of myocardial necrosis due to prolonged acute ischemia [3]. While the development of surgical and pharmacological methods for treating CHD has increased patient survival rates, individuals who have suffered from an MI remain at a high risk of experiencing post-infarction complications and a decline in their quality of life [4]. After an MI, the heart activates local compensatory mechanisms that result in decreased myocardial metabolism, which can lead to the development of heart failure and potentially, sudden death [5]. Patients with severe left ventricular myocardial dysfunction, with an ejection fraction of less than 35% due to post-infarction cardiac remodeling, represent the most severe category of patients among those with CHD [6, 7]. The primary treatments for CHD include pharmacotherapy and surgical revascularization of the myocardium [8]. Although timely reperfusion and thrombol therapy can slow the adverse progression of cardiac remodeling, these treatments cannot completely restore myocardial structure, and the ultimate goal of treatment is to achieve remission [9]. When the disease reaches advanced stages, heart transplantation remains the only effective treatment method. However, the possibilities of implementing heart transplantation are restricted by strict selection criteria and limited availability of donor organs. As a result, the field of cardiac surgery has focused on finding and implementing new approaches to restore blood circulation in ischemic areas of the myocardium for many years [10]. Cell therapy methods show great potential for restoring myocardial function, providing patients with an additional restorative treatment option in conjunction with currently used surgical and pharmacological methods (Figure 1). The first trials of cell therapy for CHD were conducted nearly two decades ago, when the primary method was to transplant various cell populations derived from adult tissues, such as skeletal muscle myoblasts [11; 12], bone marrow mesenchymal stromal cells (MSCs) [13; 14], hematopoietic stem cells (HSCs) [15; 16] and endothelial progenitor cells (EPCs) [17]. In the early 2000s, a group of scientists led by [PERSON] described c-Kit-positive cardiac cells and their potential for treating CHD [18]. While it was initially thought that these cells could differentiate into cardiomyocytes, endothelial cells and smooth muscle cells, this hypothesis has yet to be confirmed [19; 20]. Currently, the regenerative effect of c-Kit-positive cells during transplantation is not fully understood and is thought to be due to the secretion of paracrine factors and stimulation of therapeutic angiogenesis [20]. The development of protocols for transplantation of cardiomyocytes or their precursors derived from in vitro differentiation of induced pluripotent stem cells (iPSCs) to replace lost myocytes is another approach to restore cardiac tissue during ischemic injury [7; 21]. Transplantation methods are being developed using various matrices or tissue-engineered structures to enhance cell survival in the recipient. To date, there are over 100 clinical trials of cell therapy for acute MI and over 90 for chronic ischemic cardiomyopathyphaties [21; 22]. The majority of these studies have shown that this type of therapy is safe, regardless of the specific cell product studied, delivery route, dosing protocol, or patient characteristics.