Stem Cell Secretome and Paracrine Activity

Abstract

Heart diseases are a major social and economic burden, as the human heart cannot regenerate after injury. Therefore, there is an urgent need for new therapeutic approaches to minimize, prevent, or reverse cardiac damage. In recent years stem cell-based approaches have gained considerable attention from scientists as well as the public. A publication by Orlic and coworkers describing that “locally delivered bone marrow cells can generate de novo myocardium, ameliorating the outcome of coronary artery disease” initiated the area of stem cell-based cardiac therapy. However, subsequent work of several independent groups revealed that neither bone marrow stem cells nor other stem cells can significantly contribute to restore lost myocardium by differentiating into cardiomyocytes. Instead, Gnecchi and coworkers have suggested that the beneficial effect of stem cell-based therapies is predominantly due to bioactive molecules secreted by the transplanted stem cells. This hypothesis has been substantiated in the last decade by accumulating evidence that factors of the stem cell secretome promote cardiomyocyte survival and proliferation, modulate the immune system, have beneficial effects on cardiac metabolism, reduce cardiac remodeling, and induce angiogenesis. These findings raise the question if stem cells are needed or whether a detailed understanding of the stem cell secretome will allow a cell-free therapy for heart diseases.