Cell transplantation--a potential therapy for cardiac repair in the future?

PURPOSE: Adult human myocardium cannot regenerate because cardiac muscle cells do not reenter the cell cycle. Myoblasts, cardiomyocytes, and stem cell-derived cardiomyocytes have been transplanted in experimental settings to replace lost myocardial tissue. The purpose of this paper is to review the experimental data about cell transfer onto myocardium and to highlight the advantages of the particular cell types used.

BACKGROUND AND METHODS: Myoblasts or satellite cells are precursor cells attached to skeletal muscle fibers. The transfer of these cells onto damaged myocardium was demonstrated successfully in several animal models. Because myoblasts can be expanded in culture, a large number of cells can be obtained from only a small skeletal muscle specimen. These cells could be delivered locally by injection within a damaged myocardial area or by coronary infusion. However, only one group has been able to show an improvement in myocardial function after myoblast transfer. The second type of cells used experimentally for cell transfer were fetal cardiomyocytes. Fetal cardiomyocytes retain the ability to divide and therefore can be expanded in culture. The cells were integrated into the myocardial tissue, differentiated into normal cardiac muscle cells, and formed intercellular connections with host myocardial cells. The transplantation of these cells onto cryo-injured myocardium resulted in improved cardiac function in several animal models. Stem cell-derived cardiomyocytes can be selected from embryonic stem cells. These cells still divide and differentiate into different cardiac muscle cells (atrial, ventricular, and pacemaker). After transplantation into damaged myocardium in mice, they formed stable grafts and survived for at least 7 weeks. The selection of these cells has to be performed with care to prevent teratoma formation originating from single undifferentiated cells attached to the transferred cells. Recent experimental studies revealed the ability of bone marrow stem cells to differentiate into cardiomyocytes. These cells were transplanted into damaged myocardium via coronary perfusion. They survived for at least 4 weeks and showed differentiation toward cardiac muscle cells. The functional benefit of bone marrow stem cells, however, has not been clearly demonstrated, and there is a possibility of tumor formations originating from these cells.

DISCUSSION: Myoblasts and bone marrow stem cell-derived cardiomyocytes would permit autologous cell transfer onto the myocardium. These cells can be easily obtained and expanded in culture. Gene transfer is also possible, and there are no ethical proscriptions against an autologous cell transfer. However, the integration and final differentiation of these cells in the heart tissue is not clear yet. Fetal cardiomyocytes, on the other hand, are integrated in the myocardial tissue, improve cardiac function, and can be expanded in culture. Their transfer would be allogenic, making immunosuppression necessary. Stem cell-derived cardiomyocytes could be used to replace all 3 types of cardiac muscle cells, and they can be expanded in culture. The possibility of teratoma formation makes a 100%- selection mandatory. At present, ethical concerns against working with human embryonic stem cells are a factor to be considered.

CONCLUSIONS: Cell transfer therapy has been shown to improve myocardial function in animal experiments. This finding indicates that a reduced myocardial function can be improved by cell transfer therapy. Stem cell-derived cardiomyocytes in particular, either of embryonic or bone marrow cell origin, would allow for selective replacement of pacemaker cells or atrial or ventricular cardiomyocytes.