Tehran University of Medical Sciences Acta Medica Iranica 0044-6025 50 12 2012 12 15 789 797 EN Iraj Ragerdi Kashani Department of Anatomical Sciences, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Azim Hedayatpour Department of Anatomical Sciences, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Parichehr Pasbakhsh Department of Anatomical Sciences, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Leya Kafami Department of Pathobiology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran. Nader Atlasi Department of Anatomical Sciences, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Vahid Pirhajati Mahabadi Department of Anatomical Sciences, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Reza Mamoudi Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran. Maryam Baazm Department of Anatomical Sciences, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. 2015 09 28 Previous studies have demonstrated the potential of monotherapy with either mesenchymal stem cells (MSCs) or estrogen in autoimmune and cuprizone models of multiple sclerosis (MS). The aim of this study was to examine the effects of co-administration of 17β-estradiol (E2) and adipose-derived mesenchymal stem cells (ADSCs) on remyelination of corpus callosum axons in a cuprizone model of MS. Forty eight male C57BL/6 mice were fed cuprizone (0.2%) for 6 weeks. At day 0 after cuprizone removal, animals were randomly divided into four groups. The E2 monotherapy, ADSCs monotherapy, E2/ADSCs combined therapy and vehicle control. Some mice of the same age were fed with their normal diet to serve as healthy control group. E2 pellets, designed to release 5.0 mg E2 over 10 days, were implanted subcutaneously. 106 PKH26 labeled ADSCs were transplanted into lateral tail. The extent of demyelination, remyelination, and cell type's composition of host brain were examined at 10 days post-transplantation in the body of the corpus callosum. Transplanted cells migrated to the corpus callosum injury. Histological examination revealed efficacy of intravenous ADSCs transplantation in remyelination of mouse cuprizone model of MS can be significantly enhanced by E2 administration. Flow cytometry showed that the mean percentages of expression of Iba-1, Olig2 and O4 were significantly increased in E2/ADSCs combined therapy in comparison with ADSCs monotherapy. In conclusion, the findings of this study revealed that E2 administration enhanced efficacy of intravenous ADSCs transplantation in remyelination of corpus callosum axons in mouse cuprizone model of MS. https://acta.tums.ac.ir/index.php/acta/article/view/3995 https://acta.tums.ac.ir/index.php/acta/article/download/3995/3970