# Cell Therapy in the Treatment of Coronary Heart Disease
## 6 Cell Dosing and Delivery  
The goal of delivering cells to the recipient's heart is to ensure that a sufficient number of viable donor cells can enter the damaged areas of the myocardium shortly after transplantation and remain for a long time, effectively integrating and functioning [21]. Currently, intramyocardial, intracoronary, and intravenous administration are commonly used interchangeably, as there is no optimal method for cell transplantation into the heart [21; 150]. The intracoronary delivery method enables direct delivery of cells to the affected regions of the myocardium via the coronary arteries [151]. This approach is usually employed during primary percutaneous coronary intervention for patients with acute MI. Using retroviral transfection with plasmids expressing GFP, [PERSON] and colleagues have demonstrated the capacity for transcoronary migration of transplanted c-Kit+ cardiac stromal cells and their subsequent engraftment into the myocardium of the recipient animal [152]. However, intracoronary administration results in washout of cells into the systemic circulation, leading to insignificant engraftment in the heart, which may be sufficient for paracrine effects but not for myocardial repair during replacement therapy [150]. Cardiomyocytes obtained through directed differentiation of iPSCs cannot be delivered in large quantities via intracoronary infusion due to the risk of microvascular occlusion [21]. Intravenous administration through peripheral injection represents the least invasive and simplest method, obviating the need for surgical or endoscopic interventions. The efficacy of intravenous administration of stem cells is dependent on the existence of a homing effect, i.e., an increase in the migration of cells to the site of myocardial damage [153]. However, it should be noted that the majority of transplanted cells from the systemic circulation enter the lungs, while only a small quantity reaches the heart, liver, and spleen [154]. Intramyocardial delivery of cells to the heart can be accomplished using two methods: transendocardial and transepicardial. The latter approach is utilized during open-heart surgery and boasts accurate delivery of cells to the intended area of the myocardium through direct visualization of the ischemic area. Transendocardial intramyocardial administration, meanwhile, presents as an efficient and minimally invasive means of cell transplantation. Cells are introduced using a special system (NOGA system), which includes a catheter with a needle and an electromechanical mapping system [155]. Transendocardial and transepicardial methods of transplanting autologous skeletal myoblasts were found to be equally effective in an experimental study modeling myocardial infarction in minipigs [156]. In a study comparing transplantation techniques for CD34+ autologous bone marrow stem cells in patients with non-ischemic dilated cardiomyopathy, intramyocardial injection resulted in higher engraftment rates in the heart than intracoronary injection [157]. However, intramyocardial injection also carries a risk of myocardial perforation [21]. Cells survive relatively poorly with current methods of cell transplant, ranging from 10 to 15 percent regardless of the number of cells implanted [158]. The investigation of the relationship between the survival of transplanted cells and the efficacy of cell therapy requires the precise monitoring of the number, distribution and fate of injected cells, and analysis of the correlation of these variables with changes in cardiac functional parameters [159]. To date, numerous studies have been conducted on experimental animals with ischemic cardiomyopathy, including mice, rats, and pigs [19; 159; 160; 161; 162; 163; 164; 165]. These studies evaluated the extent of cell engraftment using histological methods, in vivo imaging, or molecular genetic analysis of heart tissue explants.