Influence of Transplantation of Genetically Engineered Microvesicles on Contractile Characteristics of Diaphragmatic Muscle of Transgenic Mice with Model of Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease which is characterized by death of motor neurons, development of muscle weakness, paralyses and atrophy of skeletal muscles. The most common immediate cause of lethal outcome of ALS patients is respiratory insufficiency due to paralysis of respiratory muscles. Effectiveness of currently used medications for ALS treatment is very limited and can extend life of patient only for few months. One of perspective directions in development of ALS therapy is use of microvesicles prepared from mesenchymal stem cells (MSC). Such microvesicles have neuroprotective properties and some advantages in comparison with parental cells (lower immune rejection, no tumor risk, etc.). Earlier we found that transplantation of MSC-derived microvesicles increases survival and reduces the severity of motor disorders in mice with ALS model. In current paper we evaluated the influence of transplantation of microvesicles obtained from mesenchymal stem cells overexpressing vascular endothelial growth factor (VEGF) and angiogenin (ANG) on contractile characteristics of diaphragmatic muscle of FUS transgenic mice with ALS model. Electrically induced single (0,1 Hz stimulation) and tetanic (5-50 Hz) muscle contractions were recorded with use of standard myographic technique on diaphragmatic muscles of 3,5-month old FUS mice after single or two time transplantation of microvesicles derived from MSC overexpressing VEGF and ANG. It was found that relative forces of single and tetanic muscle contractions were significantly increased in FUS mice received single time transplantation of microvesicles carrying VEGF and ANG comparing to FUS mice without treatment. No significant effects of treatment with microvesicles carrying VEGF and ANG on the threshold of diaphragmatic muscle contraction was found. Thus, transplantation of microvesicles carrying VEGF and ANG increases the contractility of diaphragmatic muscle of FUS mice, which should be beneficial in ALS-modelled pathology and can be one of mechanisms of therapeutic effects of microvesicles carrying VEGF and ANG on FUS mice with ALS model.