The cardiac atrial appendage stem cell: a new and promising candidate for myocardial repair

Abstract

Considerable shortcomings in the treatment of myocardial infarction (MI) still exist and therefore mortality remains high. Cardiac stem cell (CSC) therapy is a promising approach for myocardial repair. However, identification and isolation of candidate CSCs is mainly based on the presence or absence of certain cell surface markers, which suffers from some drawbacks. In order to find a more specific and reliable identification and isolation method, we investigated whether CSCs can be isolated based on the high expression of aldehyde dehydrogenase (ALDH). An ALDH(+) stem cell population, the cardiac atrial appendage stem cells (CASCs), was isolated from human atrial appendages. CASCs possess a unique phenotype that is clearly different from c-kit(+) CSCs but that seems more related to the recently described cardiac colony-forming-unit fibroblasts. Based on immunophenotype and in vitro differentiation studies, we suggest that CASCs are an intrinsic stem cell population and are not mobilized from bone marrow or peripheral blood. Indeed, they possess a clonogenicity of 16% and express pluripotency-associated genes. Furthermore, compared with cardiosphere-derived cells, CASCs possess an enhanced cardiac differentiation capacity. Indeed, differentiated cells express the most important cardiac-specific genes, produce troponin T proteins, and have an electrophysiological behaviour similar to that of adult cardiomyocytes (CMs). Transplanting CASCs in the minipig MI model resulted in extensive cardiomyogenic differentiation without teratoma formation. We have identified a new human CSC population able to differentiate into functional CMs. This opens interesting perspectives for cell therapy in patients with ischaemic heart disease.