Influence of Stem Cell Therapy on Statin-induced Myopathy of Skeletal Muscle in Female Rats
Ayat Allah Farouk1, Fawzia El-Stoohy2, Sharifa El-Arab Ali2, Hanaa Abd El-Atty2, Leila Rashed3, Noha Abo krysha4, Shaymaa Mohammed2
1Cairo University Clinical Faculty of Medicine, Neurophysiology Department, Egypt
2al-Azhar University Faculty of Medicine For Girls, Physiology Department, Egypt
3Cairo University Faculty of Medicine, Biochemistry Department, Cairo, Egypt
4Cairo University Faculty of Medicine, Neurology Department, Cairo, Egypt
Keywords: Mesenchymal stem cells, simvastatin induced myopathy, EMG, female rats
Abstract
OBJECTIVE: Objective: this work is a trial to visualize the role of transplanted BM- MSCs in skeletal muscle regeneration after induction of myopathy using a model of statin induced myopathy. The study was carried on eighty female and ten male albino rats, male rats for isolation of MSCs and female rats were divided to 8 groups.
METHODS: Materials and Methods: : Group I: Rats were administered 0.5% carboxymethyl cellulose (solvent), 25 mg/kg b.w./day, as a control group. Group II: Rats were administered simvastatin, 80 mg/kg b.wt./day, for 16 days, then were sacrificed immediately. Group III: Simvastatin, was administered for 16 days, and then rats were sacrificed after 14 days of stoppage of simvastatin. Group IV: Simvastatin was administered for 16 days, then rats were sacrificed after 30 days of stoppage of simvastatin. Group V: Simvastatin, was administered for 30 days, then rats were sacrificed immediately. Group VI: Simvastatin was administered for 30 days, with intravenous injection of mesenchymal stem cells at 16th day of the experiment. Group VII: Simvastatin was administered for 46 days, then rats were sacrificed immediately. Group VIII: Simvastatin was administered for 46 days, with intravenous injection of mesenchymal stem cells at 16th day of the experiment. On the morning of the last day of each experimental period needle EMG and NC were recorded in gastrocnemius muscle and sciatic nerve. Then rats were sacrificed and blood samples were collected. The gastrocnemius muscles of both limbs were dissected. The right gastrocnemius was processed for histological study and the left one was used for examination of MSCs homing by detection of sry gene using PCR technique.
RESULTS: Results: Stoppage of simvastatin for 14 and 30 days after induction of myopathy caused marked improvement and regeneration of skeletal muscle as manifested by significant improvement in EMG findings. However, there was persistence of mild myopathic changes after simvastatin cessation, indicating partial recovery. MSCs were injected once at the 16th day of the experiment. The transplantation of MSCs to myopathic rats, with continuous simvastatin administration, induced significant improvement and regeneration. The improvement recorded in EMG 30 days after MSCs injection was significantly better than that observed after 14 days. The light microscopic findings were markedly improved within 14 and 30 days after MSCs injection.
CONCLUSION: Conclusions: MSCs injection in myopathic rats caused improvement of skeletal muscle function with pronounced regeneration.