Response to Letter Regarding Article, “Patient Characteristics and Cell Source Determine the Number of Isolated Human Cardiac Progenitor Cells”
We thank Dr Opolski and his colleagues for their kind words and interest in our research. Although our work is the largest analysis of cardiac tissue samples to date, we are aware of the small number of patients who donated samples from more than 1 area, as well as the relatively small number of samples from the right and left ventricles. This issue was clearly stated in the text and presented in Figure 1 and Table 1.1 A multilevel mixed model was selected because, considering the alternatives, it was the most appropriate test for data clustered within patients who contributed specimens from 2 or more sites. We also used other statistical models such as the Kruskal-Wallis test and a multivariate linear model with a stepwise selection procedure. In all of these tests, the right atrium emerged as the best source of c-kit–positive cells. Moreover, after we applied a multivariable regression model and accounted for clinical characteristics, the right atrium remained the best source.1
We agree that the small number of samples from the right ventricle is a limitation. Opolski et al suggest that the right ventricle is a more viable source of cardiac progenitors because of the feasibility of percutaneous right ventricular biopsy. However, percutaneous right ventricular biopsy samples are obtained from the endocardial side of the septum. Cardiac stem cells, on the other hand, are most likely to be located at the epicardial surface of the heart.2 Thus, right ventricular biopsy as suggested by Opolski et al might miss the target cells.
Finally, we agree with Opolski et al that the majority of samples were derived from different patients with different diseases. Although interpatient variation was adjusted by multivariable linear regression, it is an inherent bias that should be taken into consideration. In addition, the absence of systematic assessment of the amount of tissue fibrosis may create a possible bias. All these limitations were addressed in our article.1
In summary, despite the recognized limitations of our work, on the basis of our findings, we suggest that the right atrium is the best source of cardiac progenitors. In view of the small number of patients and samples in our original work, we are looking forward to confirmation of our findings in a larger population of patients with heart disease.