Bone marrow stem cells are key regulators of cardiac repair following MI

Fazel S et al. (2006) Cardioprotective c-kit+ cells are from the bone marrow and regulate the myocardial balance of angiogenic cytokines. J Clin Invest 116: 1865–1877

Bone marrow stem cell therapy following myocardial infarction (MI) has shown promise in recent clinical trials for cardiac regeneration, but the mechanisms of benefit are uncertain. To better understand the processes involved, Fazel et al. looked at endogenous myocardial repair involving the c-kit receptor—known to be expressed on bone marrow stem cells and putative cardiac stem cells—in a c-kit mutant Kit^W/Kit^W-v mouse model.

Wild-type control mice with induced MI had an increased number of c-kit⁺ cells in their heart that were identified as being of bone marrow origin. These recruited bone marrow c-kit⁺ cells were associated with increased proangiogenic cytokines, including vascular endothelial growth factor, around the infarct zone. Resulting endothelial mitogenesis in these areas was associated with the establishment of extensive myofibroblast-rich repair tissue. Mutations in the c-kit receptor in Kit^W/Kit^W-v mice interfered with the mobilization of the c-kit⁺ cells to the heart, prevented angiogenesis, reduced the formation of repair tissue, and led to cardiac failure and death. Irradiation followed by transplantation with wild-type bone marrow rescued the cardiomyopathic phenotype in Kit^W/Kit^W-v mice.

The authors conclude that these results implicate bone marrow c-kit⁺ cells as key regulators of the angiogenic switch seen in infarcted myocardium and, therefore, of efficient cardiac repair. These findings have implications for the use of allogenic bone marrow transplantation in MI, especially given that only temporary engraftment of the cells is needed.