The dying stem cell hypothesis: immune modulation as a novel mechanism for progenitor cell therapy in cardiac muscle.

Stem cell transplantation after myocardial infarction has been claimed to restore cardiac function, but the underlying mechanism remains unclear. A minority of transplanted cells become adherent in heart tissue and contribute to neovascularization, whereas many donor cells die from apoptosis. We propose that apoptosis of transplanted cells modulates local tissue reactions. Apoptotic cells impact on immune reactivity by down-regulating innate and adaptive immunity, deactivating macrophages and dendritic cells, and stimulating regulatory T cells. This leads to reduced scar formation, repressed myocardial apoptosis, and improved cardiac outcome.