Bone marrow contribution to skeletal muscle: A physiological response to stress

Adult bone marrow-derived stem cells (BMDC) have been shown to contribute to numerous tissues after transplantation into a new host. However, whether the participation of these cells is part of the normal response to injury remains a matter of debate. Using parabiotically joined pairs of genetically labeled and wildtype mice, we show here that irradiation-induced damage of the target tissue, injection of bone marrow into the circulation, and immunological perturbation that are consequences of bone marrow transplantation are not necessary for bone marrow contribution to myofibers. Moreover, severe toxin-induced damage is not a prerequisite, as BMDC contribution to muscle is enhanced in response to increased muscle activity resulting from muscle overloading or forced exercise. Indeed, these two forms of muscle stress result in much more rapid contribution (within 1 month) than voluntary running (6 months). These results indicate that BMDC contribute to myofibers in response to physiologic stresses encountered by healthy organisms throughout life.