Abstract

 

Cardiac regeneration with adult stem cell (ASC) therapy is one of the promising fields to address advanced cardiovascular diseases. In addition, extracellular vesicles (EVs) from ASCs have been implicated to act as paracrine factors improving cardiac functions in ASC therapy. In our work, we isolated human cardiac mesenchymal stromal cells (h-CMSCs), through 3D dynamic tissue culture during ex vivo expansion of cardiac tissue, to compare the functional efficacy with human bone marrow derived mesenchymal stem cells (h-BM-MSCs), one of the actively studied ASCs. We characterized the h-CMSCs as CD90low, c-kitnegative, CD105positive phenotype and these cells express NANOG, SOX2, and GATA4. To determine the more effective type of EVs for angiogenesis among different sources of ASCs, we isolated EVs to evaluate the efficacy of those derived from CMSCs with either normoxic or hypoxic condition and BM-MSCs. Our results demonstrated that EVs from hypoxia treated CMSCs showed the most augmented ability of in vitro tube formation. Importantly, the extent of tube formation was even greater with EVs from CMSCs with hypoxia treatment than with EVs from BM-MSCs and comparable to human vascular endothelial growth factor. Therefore, we present here that CD90low, c-kitnegative, CD105positive CMSCs under hypoxic conditions secrete the functionally superior EVs for in vitro angiogenesis, and our findings will draw more insights on understanding myocardial repair.