Recovery of electrogenesis in skeletal muscles after cell therapy of myodystrophy in MDX mice

Кравцова, В. В.; Михайлов, В. М.; Sokolova, A. V.; Михайлова, Е. В.; Timonina, N A; Никольский, Е. Е.; Кривой, И. И.

doi:10.1134/s0012496611060093

Cited by 8 publications

(3 citation statements)

References 11 publications

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“…After cell therapy, the amplitude-time characteristics of MEPPs were returned to the control values [60]. This may indicate a connection between the structure and function of NMJs and the synthesis of dystrophin in muscle fibers [50,59,60]. The results of the present study indicated that the restoration of the structure of NMJs in mdx mice after BMC transplantation is preserved for 9 and 12 months after transplantation during the period where the number of dystrophin-positive SMFs decreases.…”

Section: Discussionsupporting

confidence: 55%

“…Our previous studies have shown improvements in the electrophysiological properties of NMJs following cell therapy. Thus, the restoration of local hyperpolarization of the postsynaptic membrane was observed in mdx mice after irradiation at a dose of 3 Gy and subsequent transplantation of bone marrow cells to the level of normal mice C57BL/6 [59].…”

Section: Discussionmentioning

confidence: 90%

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Accumulation of Dystrophin-Positive Muscle Fibers and Improvement of Neuromuscular Junctions in mdx Mouse Muscles after Bone Marrow Transplantation under Different Conditions

Sokolova

Домнина

Mikhailov

2023

IJMS

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Duchenne muscular dystrophy (DMD) is a severe muscular disorder caused by mutations in the dystrophin gene. It leads to respiratory and cardiac failure and premature death at a young age. Although recent studies have greatly deepened the understanding of the primary and secondary pathogenetic mechanisms of DMD, an effective treatment remains elusive. In recent decades, stem cells have emerged as a novel therapeutic product for a variety of diseases. In this study, we investigated nonmyeloablative bone marrow cell (BMC) transplantation as a method of cell therapy for DMD in an mdx mouse model. By using BMC transplantation from GFP-positive mice, we confirmed that BMCs participate in the muscle restoration of mdx mice. We analyzed both syngeneic and allogeneic BMC transplantation under different conditions. Our data indicated that 3 Gy X-ray irradiation with subsequent BMC transplantation improved dystrophin synthesis and the structure of striated muscle fibers (SMFs) in mdx mice as well as decreasing the death rate of SMFs. In addition, we observed the normalization of neuromuscular junctions (NMJs) in mdx mice after nonmyeloablative BMC transplantation. In conclusion, we demonstrated that nonmyeloablative BMC transplantation could be considered a method for DMD treatment.

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Section: Discussionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 90%

Accumulation of Dystrophin-Positive Muscle Fibers and Improvement of Neuromuscular Junctions in mdx Mouse Muscles after Bone Marrow Transplantation under Different Conditions

Sokolova

Домнина

Mikhailov

2023

IJMS

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“…Value of local hyperpolarization of the end-plate reached 3.7 ± 0.9 mV. It is typical for the wild-type animals and is a reliable indicator of normal functioning of a neuromuscular synapse [42,43] after BM transplantation ( Table 4).…”

Section: Discussionmentioning

confidence: 84%

Non-myeloablative Bone Marrow Stem Cell Transplantation for mdx Mice Myodystrophy Therapy

Mikhailov¹,

Sokolova²,

Кравцова³

et al. 2012

J Cell Sci Ther

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muscle and participate in muscle repair [12,13] and in muscle of mdx mice after BM stem cells transplantation [6].Except blood and muscle cells BM stem cells are also involved in the cell differentiation and regeneration in lungs, liver, skin, gastrointestinal tract and of epithelium of thyroid gland [6,14,15].Irradiation is a mandatory preliminary step of BM stem cells Abstract Background: Mdx mice are experimental model of cureless human monogenic disease Duchenne Muscular Dystrophy (DMD). Hope for а cure is associated with the use of stem cells therapy particular but not exclusively. Analysis of multiple experimental results shows what intramuscularly transplantation of different types of cells of different origins with stem cells properties can't convert mutant striated muscles fibers (SMF) into wild type SMF. It was concluded that only replacement of mutant bone marrow (BM) by wild type BM cells can convert mutant SMF into SMF of wild type. Unfortunately X-ray irradiation of mdx mice at a lethal dose of 11, 7 or 5 Gy followed by transplantation of wild C57BL/6 mice BM cells did not increase SMF dystrophin synthesis. The aim of this study was to analyse a dystrophin synthesis by mdx mice striated muscles after x-ray irradiation with the dose of 3 Gy followed by C57BL/6 bone marrow cells transplantation. Also we investigate the reparation of structure of diaphragm muscle fibers NMJs. To confirm the functional significance of observed structural changes of NMJs an investigation of resting membrane potential of diaphragm muscle fiber NMJs was also conducted.Methods: 1-1.5 months old mdx mice were irradiated by x-ray at a dose of 3 Gy. Next day freshly prepared BM cells were injected intravenously in the amount of (15-20) x 10 6 cells per mouse. Animals were studied through 2, 4, and 6 months after transplantation. Each experimental group of mice included 3-8 animals. Mus. quadriceps femoris and diaphragm muscle fibers with their nerve-muscle junctions (NMJs) were under investigation.For chimerism registration a special study was conducted using transplantation of GFP-positive C57BL/6 BM cells to mdx mice after 3 Gy irradiation. Through 6 months BM cells were separated from long bones and smears were prepared. After carbinol fixation smears were stained by propidium iodide and studied on confocal microscope LSM 5 Pascal (Carl Zeiss, Germany) to count the part of GFP-positive cells in relation to whole quantity of nuclear cells. Results:We observed a stable growth of dystrophin synthesis after nonlethal X-ray irradiation at a dose of 3 Gy. The part of dystrophin positive SMF of M. quadriceps femoris increased from 1% up to 4% (2 months), 12% (4 months) and 27% (6 months) after transplantation. Growth of dystrophin synthesis was accompanied by the decrease of SMF death level, by increase of part of SMF without central nuclear up to 22%, by accumulation of MNJ branches and by reparation of resting membrane potentials. The part of GFP-positive cells between all cells with nuclear on the BM smears of chimeric GFP tran...

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Regulatory function of the Na,K-ATPase α2-isoform

Кривой

2012

BIOPHYSICS

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Recovery of electrogenesis in skeletal muscles after cell therapy of myodystrophy in MDX mice

Cited by 8 publications

References 11 publications

Accumulation of Dystrophin-Positive Muscle Fibers and Improvement of Neuromuscular Junctions in mdx Mouse Muscles after Bone Marrow Transplantation under Different Conditions

Accumulation of Dystrophin-Positive Muscle Fibers and Improvement of Neuromuscular Junctions in mdx Mouse Muscles after Bone Marrow Transplantation under Different Conditions

Non-myeloablative Bone Marrow Stem Cell Transplantation for mdx Mice Myodystrophy Therapy

Regulatory function of the Na,K-ATPase α2-isoform

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