Bone marrow mesenchymal cells improve muscle function in a skeletal muscle re-injury model

Skeletal muscle injury is the most common problem in orthopedic and sports medicine, and severe injury leads to fibrosis and muscle dysfunction. Conventional treatment for successive muscle injury is currently controversial, although new therapies, like cell therapy, seem to be promise. We developed a model of successive injuries in rat to evaluate the therapeutic potential of bone marrow mesenchymal cells (BMMC) injected directly into the injured muscle. Functional and histological assays were performed 14 and 28 days after the injury protocol by isometric tension recording and picrosirius/Hematoxilin & Eosin staining, respectively. We also evaluated the presence and the fate of BMMC on treated muscles; and muscle fiber regeneration. BMMC treatment increased maximal skeletal muscle contraction 14 and 28 days after muscle injury compared to non-treated group (4.5 ± 1.7 vs 2.5 ± 0.98 N/cm2, p<0.05 and 8.4 ± 2.3 vs. 5.7 ± 1.3 N/cm2, p<0.05 respectively). Furthermore, BMMC treatment increased muscle fiber cross-sectional area and the presence of mature muscle fiber 28 days after muscle injury. However, there was no difference in collagen deposition between groups. Immunoassays for cytoskeleton markers of skeletal and smooth muscle cells revealed an apparent integration of the BMMC within the muscle. These data suggest that BMMC transplantation accelerates and improves muscle function recovery in our extensive muscle re-injury model

Bone marrow mesenchymal cells improve muscle function in a skeletal muscle re-injury model.

Skeletal muscle injury is the most common problem in orthopedic and sports medicine, and severe injury leads to fibrosis and muscle dysfunction. Conventional treatment for successive muscle injury is currently controversial, although new therapies, like cell therapy, seem to be promise. We developed a model of successive injuries in rat to evaluate the therapeutic potential of bone marrow mesenchymal cells (BMMC) injected directly into the injured muscle. Functional and histological assays were performed 14 and 28 days after the injury protocol by isometric tension recording and picrosirius/Hematoxilin & Eosin staining, respectively. We also evaluated the presence and the fate of BMMC on treated muscles; and muscle fiber regeneration. BMMC treatment increased maximal skeletal muscle contraction 14 and 28 days after muscle injury compared to non-treated group (4.5 ± 1.7 vs 2.5 ± 0.98 N/cm2, p<0.05 and 8.4 ± 2.3 vs. 5.7 ± 1.3 N/cm2, p<0.05 respectively). Furthermore, BMMC treatment increased muscle fiber cross-sectional area and the presence of mature muscle fiber 28 days after muscle injury. However, there was no difference in collagen deposition between groups. Immunoassays for cytoskeleton markers of skeletal and smooth muscle cells revealed an apparent integration of the BMMC within the muscle. These data suggest that BMMC transplantation accelerates and improves muscle function recovery in our extensive muscle re-injury model

Effects of 10 days of ovariectomy on hormone concentration and body composition.

<p>Ovx—rats submitted to ovariectomy for 10 days.</p><p>** p<0.01 compared to sham group</p><p>Effects of 10 days of ovariectomy on hormone concentration and body composition.</p

Post-exercise growth hormone secretion.

<p>Values are mean ± SEM (n = 10). *p<0.05 vs basal (non-exercised group) analyzed by one-way analysis of variance followed by the Dunnett’s multiple comparison test.</p

Impact of D1 inhibition by PTU on circulating levels of growth hormones.

<p>Values are mean ± SEM. Sample size is shown in parenthesis. *p<0.05 analyzed by two-way ANOVA followed by the Bonferroni multiple comparison test.</p

Effects of 10d of ovariectomy (Ovx) on maximal aerobic capacity and blood lactate concentration.

<p>S_max—maximal speed (n = 18); [La]—lactate concentration (n = 5)</p><p>* p<0.05 compared to Basal group</p><p>Effects of 10d of ovariectomy (Ovx) on maximal aerobic capacity and blood lactate concentration.</p

Characteristic of the acute exercise session.

<p>Ovx—rats submitted to ovariectomy for 10 days; S_max—maximal speed; [La]—lactate concentration</p><p>* p<0.05 compared to Basal group</p><p>Characteristic of the acute exercise session.</p

Type 2 iodothyronine deiodinase is upregulated in rat slow- and fast-twitch skeletal muscle during cold exposure

During cold acclimation, shivering is progressively replaced by nonshivering thermogenesis. Brown adipose tissue (BAT) and skeletal muscle are relevant for nonshivering thermogenesis, which depends largely on thyroid hormone. Since the skeletal muscle fibers progressively adapt to cold exposure through poorly defined mechanisms, our intent was to determine whether skeletal muscle type 2 deiodinase (D2) induction could be implicated in the long-term skeletal muscle cold acclimation. We demonstrate that in the red oxidative soleus muscle, D2 activity increased 2.3-fold after 3 days at 4°C together with the brown adipose tissue D2 activity, which increased 10-fold. Soleus muscle and BAT D2 activities returned to the control levels after 10 days of cold exposure, when an increase of 2.8-fold in D2 activity was detected in white glycolytic gastrocnemius but not in red oxidative gastrocnemius fibers. Propranolol did not prevent muscle D2 induction, but it impaired the decrease of D2 in BAT and soleus after 10 days at 4°C. Cold exposure is accompanied by increased oxygen consumption, UCP3, and PGC-1α genes expression in skeletal muscles, which were partialy prevented by propranolol in soleus and gastrocnemius. Serum total and free T3 is increased during cold exposure in rats, even after 10 days, when BAT D2 is already normalized, suggesting that skeletal muscle D2 activity contributes significantly to circulating T3 under this adaptive condition. In conclusion, cold exposure is accompanied by concerted changes in the metabolism of BAT and oxidative and glycolytic skeletal muscles that are paralleled by type 2 deiodinase activation

G-CSF does not improve systolic function in a rat model of acute myocardial infarction

OBJECTIVEGranulocyte colony-stimulating factor (G-CSF) has been reported to improve cardiac performance by increasing the number of bone marrow stem cell in the peripheral circulation. The aim of this study was to investigate the impact of G-CSF administration on cardiac function in a rat model of acute myocardial infarction.METHODSRecombinant human G-CSF (Filgrastim, 100 microg/kg, sc) twice a day during seven consecutive days (G-CSF group, n=13) or vehicle (control group, n=10) was administrated three hours after left anterior coronary artery ligation. Cardiac performance was evaluated 19-21 days after myocardial infarction by electro- and echocardiography, hemodynamic and treadmill exercise test.RESULTSBoth infarcted groups exhibit impaired cardiac function compared to sham-operated rats. Moreover, all cardiac functional parameters were not statistically different between G-CSF and infarcted group at resting conditions as well as after treadmill exercise stress test. There was no sign of cardiac regeneration and infarct size was not different on histological analysis between groups.CONCLUSIONSThese data clearly shows that G-CSF treatment was unable to prevent cardiac remodeling or to improve cardiovascular function in a rat model of acute myocardial infarction, by permanent LAD ligation, despite bone marrow stem cell mobilization

Immunolocalization of smooth muscle myosin as vessel marker in soleus muscle treated with BMMC 28 days after repeated injuries.

<p>A) and (D) Differential interference contrast images; (B) and (E) overlay images of Hoestch (in blue) and smooth muscle myosin (green) staining; (C) and (F) smooth muscle myosin alone. Green fluorescence indicates typical vessel shape labelling pattern while nuclei are shown by blue Hoescht staining. Arrows denote nuclei position. Bars correspond to 20μm.</p