Role of transplanted bone marrow cells in response to skeletal muscle injury.

The recently discovered capacity of bone marrow cells (BMCs) to contribute to injury-induced skeletal muscle regeneration has brought new possi- bilities in the treatment of skeletal muscle diseases. However, a suitable method of BMC transplantation usable for such therapy has to be established. In this work, recipient mice were intramuscularly injected with cardiotoxin, then whole-body lethally irradiat- ed to eradicate satellite cells in their injured tibialis anterior (TA) muscles and to suppress haematopoie- sis, and subsequently intravenously transplanted with lacZ + BMCs with the aim to investigate the role of exogenous BMCs in response to skeletal muscle injury. Seven to 33 days after grafting, recipient TA muscles were examined to detect donor-derived X-gal + cells and analysed by quantitative PCR. In in- jured recipients' muscles, X-gal positivity was identi- fied 14 and 33 days after grafting in some infiltrating neutrophils and macrophages, infrequently in fi- broblasts of endomysium, and in many large multi- nucleated cells (devoid of myogenic markers desmin and nestin) resembling foreign body giant cells situ- ated in the vicinity of necrotic muscle fibres. qPCR confirmed the presence of transplanted lacZ + BMCs in injured recipients' muscles. Our results proved the ability of intravenously transplanted adult BMCs to settle in injured muscles and generate blood cells that infiltrated endomysium and took part in the cleaning reaction. After inhibition of endogenous myogenesis, BMCs were not able to participate in formation of new muscle fibres due to persisting necrosis of degenerated muscle fibres. Instead, BMCs attempted to resorb necrotic structures, which con- firmed the indispensable role of bone marrow-de- rived macrophages in skeletal muscle regeneration.