Structure of neuromuscular junctions and differentiation of striated muscle fibers in mdx mice after bone-marrow stem cell therapy

Abstract

Mdx mice are a model of Duchenne muscular dystrophy caused by deficiency of dystrophin. Muscles of mdx mice are characterized by high levels of striated muscle fibers death and, accordingly, by a high level of its regeneration. Moreover, the structure of neuromuscular junctions in mdx mice is altered. Changes in the structure of mdx mice neuromuscular junctions against a background of increasing differentiation of striated muscle fibers after C57BL/6 Lin (-) bone marrow stem cells transplantation were investigated. The muscles were studied in 4, 8, 16 and 24 weeks after transplantation. We observed that the level of striated muscle fibers loss was decreased from the 4th week after transplantation of bone marrow stem cells. Accumulation of muscle fibers without centrally located nuclei began from the 8th week, and dystrophin synthesis was increased at the 16th and 24th weeks after bone marrow stem cells transplantation. Longitudinal sections of quadriceps muscles of mdx mice showed decrease in the number of acetylcholine receptors clusters in neuromuscular junctions and a simultaneous increase in acetylcholine receptor clusters area during the 4th week after transplantation. In 16 weeks after bone marrow stem cells transplantation, total neuromuscular junction area was increased due to increase in the area of acetylcholine receptors clusters and to increase in their number as well. Thus, single intramuscular transplantation of C57BL/6 Lin (-) bone marrow stem cells induces an increase in differentiation of mdx mice striated muscle fibers and improves the structure of neuromuscular junctions.