Cardiac Regenerative Medicine

ociety is increasingly affected by degenerative diseases that need to be treated by modern medicine. In the advanced stages of such diseases, modalities for cure are often not available. Heart disease is the primary cause of death throughout the world, despite dramatic improvements that have been made in the treatment of cardiovascular diseases over the past decades. At present, heart transplantation and ventricular assist devices are the last line of therapy for patients with disparate types of heart failure. Heart transplantation is the definitive treatment, with survival rates of 86.1% at 1 year and 78.3% at 3 years. 1 However, several problems are associated with transplantation as a therapeutic modality, including a shortage of donors (in Japan, fewer than 10 transplantations are performed each year), long waiting period, infection, and carcinogenesis because of immunosuppressive drugs, as well as concerns about organ commercialism. 2 Ventricular assist devices represent an alternative to heart transplantation, with the capability to function as a bridge-to-transplantation, destination therapy3 or bridge-to-recovery in certain cases of dilated cardiomyopathy. 4 Although device-based therapy also has disadvantages, such as durability, infection, hemorrhage, and neurological events, several types of implantable ventricular assist devices have been released and have demonstrated excellent survival and quality of life. In Japan, clinical trials using the EVAHEART, 5 Jarvik 2000, 6 and DuraHeart7 have been completed for premarket approval. Since the 1960s, numerous experiments using amphibians8 and newts9 have clearly demonstrated the regenerative potential of the heart. However, the concept that homeostasis may be maintained in the adult heart with cell renewal capacity via the stem cell system has been challenged by a series of experiments claiming the heart to be a non-regenerative organ. The regenerative capability of the heart is not sufficient to compensate for myocardial cell loss following infarction. Recently, there have been many reports of pluripotent stem cells/progenitors obtained from diverse fetal and adult tissues, ranging from skeletal muscle and bone marrow to amniotic fluid, placenta, umbilical cord, and fetus. Many investigators have demonstrated that murine bonemarrow-derived stem cells/progenitors carry over their transdifferentiation ability to generate an array of progeny cells, including osteocytes, chondrocytes, skeletal muscle cells, cardiac muscle cells, hepatocytes, and neurons. 10 On the basis of many promising experimental investigations examining the feasibility and efficacy of transplantation of stem cells/progenitors in patients with heart disease, randomized controlled trials using somatic stem/progenitor cell transplantation for heart disease have been reported. The results do not uniformly demonstrate effectiveness in improving cardiac function. However, the safety issues have been addressed through these clinical trials, which involved more than 1,000 patients who underwent regenerative therapy. The issues that remain to be solved include delivery methods, conditioning of the host, timing of implantation, and dose of cells, as well as cell population. This review explores the recent scientific and clinical advances that are likely to have a strong impact on regenerative medicine in the field of cardiology. In particular, we discuss the stem cell system in the heart and the mechanisms of cell therapy for heart diseases.