Potential and clinical utility of stem cells in cardiovascular disease.

The recent identification of bone marrow-derived adult stem cells and other types of stem cells that could improve heart function after transplantation have raised high expectations. The basic mechanisms have been studied mostly in murine models. However, these experiments revealed controversial results on transdifferentiation vs transfusion of adult stem cells vs paracrine effects of these cells, which is still being debated. Moreover, the reproducibility of these results in precisely translated large animal models is still less well investigated. Despite these weaknesses results of several clinical trials including several hundreds of patients with ischemic heart disease have been published. However, there are no solid data showing that any of these approaches can regenerate human myocardium. Even the effectiveness of cell therapy in these approaches is doubtful. In future we need in this important field of regenerative medicine: i) more experimental data in large animals that are closer to the anatomy and physiology of humans, including data on dose effects, comparison of different cell types and different delivery routes; ii) a better understanding of the molecular mechanisms involved in the fate of transplanted cells; iii) more intensive research on genuine regenerative medicine, applying genetic regulation and cell engineering.