The potential therapeutic effect of adipose tissue-derived mesenchymal stem cell transplantation on cuprizone model of multiple sclerosis in the mice

Abstract

Background: Multiple Sclerosis (MS) is an autoimmune neurodegenerative disease. Current treatments have limited effect on the upstream pathophysiology of the disease. Nowadays, mesenchymal stem cells are considered to be a potential therapeutic tool for various neurodegenerative diseases. Their immune privileged status, trophic nature, and capacity to differentiate into various lineages makes them an ideal vehicle for treatment options. Aim of the Study: the goal of this study was to assess the remyelinating potential of adipose mesenchymal stem cells (AD-MSCs) in cuprizone model of MS. Material and Methods: AD-MSCs were obtained from male mice and characterized by flow cytometry. Thirty-six female C57BL/6 mice were divided equally among three groups. Group I (control group): mice were fed with a normal diet through the entire duration of the experiment. Groups II and III: mice were fed with a 0.2 % cuprizone containing diet for six weeks. By the end of the sixth week, group II and III mice received a single intravenous injection of 500 µl of a complete culture medium and 1 × 106 AD-MSCs suspended in 500 µl of a complete culture medium respectively. Neurological tests were done before and 9-10 days after the injection. All mice were euthanized at day 10 and corpus callosum was processed for further histological and biochemical examination. Morphometric study was done to assess remyelination. Migration of the male AD-MSCs into the female mice brain was confirmed by SRY gene expression. The obtained data were further statistically analyzed. Results: Cuprizone intake for 6 weeks caused extensive demyelination similar to MS accompanied by neurological deficits and change in the oxidative stress. Intravenous administration of AD-MSCs in group III enhanced the remyelination process improved the motor and cognitive functions and decrease the oxidant level. Conclusion: AD-MSCs provide a valuable potential treatment for neurodegenerative demyelinating diseases such as MS.