Influence of Stem Cell Therapy on Statin-induced Myopathy of Skeletal Muscle in Female Rats

Abstract

Ad dress for Cor res pon den ce/Ya z›fl ma Ad re si:Objective: This is a trial to visualize the role of transplanted bone marrow mesenchymal stem cells (BM-MSCs) in skeletal muscle regeneration after induction of myopathy using a model of statin induced myopathy. Ma te ri al and Met hod: The study was conducted in eighty female and ten male albino rats, male rats for isolation of MSCs and female rats were divided to 8 groups. Group I was administered 0.5% carboxymethyl cellulose (solvent), 25 mg/kg b.w./day, as a control group. Group II was administered simvastatin, 80 mg/kg b.wt./day, for 16 days, then was sacrificed immediately. Group III was administered simvastatin 80 mg/kg b.wt/day, for 16 days, and then the rats were sacrificed 14 days after discontinuing simvastatin. Group IV was administered simvastatin 80 mg/kg b.wt/day for 16 days, then the rats were sacrificed 30 days after discontinuing simvastatin. Group V was administered simvastatin for 30 days, then the rats were sacrificed immediately. Group VI was administered simvastatin for 30 days, with intravenous injection of mesenchymal stem cells on day 16. Group VII was administered simvastatin for 46 days, then the rats were sacrificed immediately. Group VIII was administered simvastatin for 46 days, with intravenous injection of mesenchymal stem cells on day 16. On the morning of the last day of each experimental period needle electromyography (EMG) and nerve conduction (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 muscle was processed for histological study and the left one was used for examination of MSCs homing by detection of sry gene using PCR technique. Re sults: Discontinuing simvastatin 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 on day 16. The transplantation of MSC to myopathic rats, with continuous simvastatin administration, induced significant improvement and regeneration. The improvement recorded in EMG 30 days after MSC injection was significantly better than that observed after 14 days. The light microscopic findings were markedly improved within 14 and 30 days after MSC injection. Dis cus si on: MSC injection in myopathic rats induced improvement of skeletal muscle function with pronounced regeneration. (Turkish Journal of Neurology 2012; 18:135-44) Özet Amaç: Bu çalışma, statin ile indüklenen miyopati modeli ile miyopati geliştirilen iskelet kasında, kemik iliği mezenkimal kök hücrelerinin (MKH) kas rejenerasyonundaki etkisini izlemek amacıyla yapılmıştır. Ge reç ve Yön tem: Çalışma 80 dişi ve 10 erkek albino sıçanda yapılmıştır. Erkek sıçanlar mezenkimal kök hücre sağlamak amacı ile kullanılmış, dişi sıçanlar da 8 gruba bölünmü...