# Cell Therapy in the Treatment of Coronary Heart Disease
## 6 Cell Dosing and Delivery
While these studies generally showed improvement in cardiac function and/or reduction in infarct area, they did not demonstrate a correlation between these parameters and the degree of cell survival at various time points [166]. Tracking or estimating the number of cells remaining after transplantation can be technically challenging during clinical trials, as it requires the utilization of non-invasive imaging techniques like MRI, PET, SPECT, and CT. Injected cells must also be pre-labeled with numerous probes and labels, which need further research on their safety prior to use [167]. Histological or molecular analysis of the recipient's myocardium can only occur in rare cases, specifically when the patient has passed away or a donated heart has undergone transplantation. Therefore, the current focus is on the correlation between the number of cells introduced and the resulting therapeutic benefit. However, several preclinical and clinical studies on cellular therapy for CHD have failed to establish a clear correlation between the number of cells transplanted and improved cardiac function [168]. [PERSON] et al. 's study demonstrated that the administration of allogeneic MSCs in pigs with induced MI through intravenous injection of three doses (1, 3, or 10 million) resulted in a more substantial enhancement in left ventricular functional parameters in groups that received higher cell doses (3 and 10 million), as opposed to the control group [169]. [PERSON] and colleagues utilized transendocardial intramyocardial administration of allogeneic MSCs at four different doses (25, 75, 225, or 450 million cells) in a sheep model of induced MI. The study found that lower doses of 25 and 75 million cells had a more pronounced beneficial effect on the heart's functional state [170]. [PERSON] and colleagues conducted a study in which cells were injected into pigs with MI via transepicardial injection during experimental open-heart surgery [171]. The researchers found that administering 200 million autologous MSCs led to a significant reduction in infarct size compared to a lower dose of 20 million. [PERSON] et al. found that transendocardial injection of allogeneic MSCs in doses of either 24 or 240 million led to a decrease in infarct area in pigs with induced MI compared to the group receiving a higher dose of 440 million cells [172]. [PERSON] et al. conducted a clinical trial to evaluate the efficacy of intracoronary administration of autologous CD34+ bone marrow cells at different doses (5, 10, or 15 million) in patients with ST-segment elevation MI [173]. The results indicated that patients who received 10 or 15 million cells experienced a significant improvement in myocardial perfusion compared to the control group. In the POSEIDON clinical trial, patients diagnosed with ischemic cardiomyopathy received transendocardial injections of allogeneic or autologous bone marrow-derived MSCs at different doses (20, 100 or 200 million). Regarding improvement of ejection fraction and left ventricular end-systolic volume, an inverse dose-dependent response to cell therapy was observed in this study [14]. It is challenging to compare the outcomes of existing clinical and experimental research studies due to variations in their design, the number of cells provided, the delivery method employed, and the timing of administration. In their meta-analysis, [PERSON] and colleagues reviewed eight randomized controlled trials of MSCs transplantation in patients with MI and subsequent percutaneous coronary artery bypass grafting. Their findings suggest that administration of no more than 10 million cells within one week of MI may optimize restoration of left ventricular systolic function [174]. However, additional clinical trials with carefully designed designs and consideration of individual patient characteristics are essential for a more precise evaluation of the appropriate cell dose and optimal timing of transplantation. To date, most clinical trials of cell therapy for the treatment of CHD have used a single dose of cells.