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Several studies have demonstrated the existence of pluripotent bone marrow–derived stem cells capable of homing to injured cardiac and skeletal muscle; however, there has been little evidence demonstrating the induction of tissue-specific endogenous genes in donor stem cells following engraftment. A new study in this issue reports an intriguing finding that raises additional concerns relating to stem cell plasticity and stem cell therapy in an already heated and controversial field. The study demonstrates that wild-type bone marrow–derived side population stem cells are indeed readily incorporated into both skeletal and cardiac muscle when transplanted into mice that lack δ-sarcoglycan — a model of cardiomyopathy and muscular dystrophy. However, these cells fail to express sarcoglycan and thus to repair the tissue, which suggests that this stem cell population has limited potential for cardiac and skeletal muscle regeneration

Fusion of bone marrow–derived stem cells with striated muscle may not be sufficient to activate muscle genes