Mesenchymal stem cells for cardiac regenerative therapy

Until recently, the concept of treating the injured or failing heart by generating new functional myocardium was considered physiologically impossible. Major scientific strides in the past few years have challenged the concept that the heart is a post-mitotic organ, leading to the hypothesis that cardiac regeneration could be therapeutically achieved. Bone marrow-derived adult stem cells were among the first cell populations that were used to test this hypothesis. Animal studies and early clinical experience support the concept that therapeutically delivered mesenchymal stem cells (MSCs) safely improve heart function after an acute myocardial infarction (MI). MSCs produce a variety of cardio-protective signalling molecules, and have the ability to differentiate into both myocyte and vascular lineages. Additionally, MSCs are attractive as a cellular vehicle for gene delivery, cell transplantation or for tissue engineering because they offer several practical advantages. They can be obtained in relatively large numbers through standard clinical procedures, and they are easily expanded in culture. The multi-lineage potential of MSC, in combination with their immunoprivileged status, make MSCs a promising source for cell therapy in cardiac diseases. Here we provide an overview of biological characteristics of MSCs, experimental animal studies and early clinical trials with MSCs. In addition, we discuss the routes of cell delivery, cell tracking experiments and current knowledge of the mechanistic underpinnings of their action.