Abstract
In this work, recipient mice were intramuscularly injected with cardiotoxin, then whole-body lethally irradiated to eradicate satellite cells in their injured tibialis anterior muscles and to suppress hematopoiesis and subsequently, intravenously transplanted with mouse donor lacZ+ bone marrow cells with the aim to investigate role of exogenous bone marrow cells in response to skeletal muscle injury. Seven to 33 days after grafting, recipient tibialis anterior muscles were examined to detect donor-derived X-gal+ cells and analyzed by quantitative PCR.
In injured recipients'' muscles, X-gal positivity was identified 14 and 33 days after grafting in some infiltrating neutrophils and macrophages, infrequently in fibroblasts of endomysium and in many large multinucleated cells (devoid of myogenic markers desmin and nestin) resembling foreign body giant cells situated in vicinity to necrotic muscle fibers. qPCR confirmed the presence of lacZ+ cells in injured recipients'' muscles. Our results proved ability of intravenously transplanted adult bone marrow cells to settle in injured muscles and generate blood cells that infiltrated endomysium and took part in the cleaning reaction.
After inhibition of endogenous myogenesis, bone marrow cells were not able to participate in formation of new muscle fibers due to persisting necrosis of degenerated muscle fibers. Instead, donor-derived cells attempted to resorb necrotic structures, which confirmed the indispensable role of macrophages originated from the bone marrow in skeletal muscle regeneration.