Skeletal muscle tissue has a remarkable capability of regenerating in pathological conditions or after injury. The principal muscle stem cells, satellite cells, are responsible for this prompt and efficient process. Normally quiescent in their niches underneath the basal lamina of each muscle fiber, satellite cells become activated to repair or form new fibers. Ideally, healthy donor stem cells could be transplanted to regenerate the skeletal muscle tissue to repair a genetic defect. However, to be efficient, cell grafting requires modulation of the host muscle environment to allow homing of, and regeneration by, donor satellite cells. Here, we provide methods to modulate the host mouse muscle environment in order to destroy or preserve the muscle niche before transplanting donor satellite cells. We also describe methods to investigate donor-derived muscle regeneration and self-renewal.