Can human cord blood-derived stem cells improve statin-induced myopathy in rats? A histological and immunohistochemical study

ABSTRACT

Primary myopathies of skeletal muscle are diseases with worldwide prevalence for which effective treatment is urgently needed. The aim of this study was to investigate the ability of human umbilical cord blood [HUCB] stem cells to repair damaged skeletal muscle in a rat model of statin-induced myopathy. This study included 24 adult male albino rats divided equally into four groups the control group; the myopathy group in which myopathy was induced by administration of simvastatin [80 mg/kg/day orally for 6 weeks]; the stem cell-treated myopathy group in which myopathy was induced by administration of simvastatin with subsequent local injection of 1×10[6] HUCB stem cells in the right gastrocnemius; and the untreated myopathy group in which myopathy was induced by administration of simvastatin and then left without treatment for 2 weeks. Specimens of the right gastrocnemius from all rats were prepared, sectioned, and subjected to H and E, Prussian blue, and Masson's trichrome stains in addition to immunohistochemical staining for alpha smooth muscle actin to reveal myofibroblasts. The area% of collagen and muscle fibers and the number of myofibroblasts/high-power field were ascertained. All measurements were statistically analyzed. The gastrocnemius of the myopathy group showed frequent necrotic and damaged muscle fibers, which were replaced by fibrous and fatty tissues. Compared with control rats, there was significant decrease in the area% of muscle fibers and significant increase in the area% of collagen and in the number of myofibroblasts. Two weeks later, there was partial repair of the muscle with no significant differences between stem cell-treated and untreated myopathy groups, which reflects the failure of stem cells to repair damaged myofibers. HUCB stem cells have poor therapeutic effect for myopathy and might be hindered by the complex environment of a severely inflamed and degenerated muscle