title: Rapamycin Augments Immunomodulatory Properties of Bone Marrow-Derived Mesenchymal Stem Cells in Experimental Autoimmune Encephalomyelitis.
abstract: The immunomodulatory and anti-inflammatory properties of bone marrow-derived mesenchymal stem cells (BM-MSCs) have been considered as an appropriate candidate for treatment of autoimmune diseases. Previous studies have revealed that treatment with BM-MSCs may modulate immune responses and alleviate the symptoms in experimental autoimmune encephalomyelitis (EAE) mice, an animal model of multiple sclerosis. Therefore, the present study was designed to examine immunomodulatory effects of BM-MSCs in the treatment of myelin oligodendrocyte glycoprotein (MOG) 35-55-induced EAE in C57BL/6 mice. MSCs were obtained from the bone marrow of C57BL mice, cultured with DMEM/F12, and characterized with flow cytometry for the presence of cell surface markers for BM-MSCs. Following three passages, BM-MSCs were injected intraperitoneally into EAE mice alone or in combination with rapamycin. Immunological and histopathological effects of BM-MSCs and addition of rapamycin to BM-MSCs were evaluated. The results demonstrated that adding rapamycin to BM-MSCs transplantation in EAE mice significantly reduced inflammation infiltration and demyelination, enhanced the immunomodulatory functions, and inhibited progress of neurological impairments compared to BM-MSC transplantation and control groups. The immunological effects of rapamycin and BM-MSC treatments were associated with the inhibition of the Ag-specific lymphocyte proliferation, CD8+ cytolytic activity, and the Th1-type cytokine (gamma-interferon (IFN-γ)) and the increase of Th-2 cytokine (interleukin-4 (IL-4) and IL-10) production. Addition of rapamycin to BM-MSCs was able to ameliorate neurological deficits and provide neuroprotective effects in EAE. This suggests the potential of rapamycin and BM-MSC combined therapy to play neuroprotective roles in the treatment of neuroinflammatory disorders.
authors.affiliation: Iranian Center of Neurological Research, Neuroscience Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mansoureh
authors.initials: M
authors.lastname: Togha
authors.affiliation: Neuroscience Research Center, Department of Anatomy, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Jahanshahi
authors.affiliation: Shefa Neuroscience Research Center, Tehran, Iran.
authors.forename: Leila
authors.initials: L
authors.lastname: Alizadeh
authors.affiliation: Shefa Neuroscience Research Center, Tehran, Iran.|Multiple Sclerosis Research Center-Neuroscience Institute, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Soodeh Razeghi
authors.initials: SR
authors.lastname: Jahromi
authors.affiliation: School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Gelareh
authors.initials: G
authors.lastname: Vakilzadeh
authors.affiliation: Iranian Blood Transfusion Organization Research Center, Tehran, Iran.
authors.forename: Bahram
authors.initials: B
authors.lastname: Alipour
authors.affiliation: Shefa Neuroscience Research Center, Tehran, Iran.|Epilepsy Research Center, Klinik und Poliklinik für Neurochirurgie, Department of Neurology, Westfälische Wilhelms-Universität Münster, Münster, Germany.
authors.forename: Ali
authors.initials: A
authors.lastname: Gorji
authors.affiliation: Infectious Diseases Research Center, Department of Microbiology, Golestan University of Medical Sciences, P.O. Box 49175-1141, Gorgan, Iran. ghaem_amir@yahoo.com.|Department of Virology, Institute Pasteur of Iran, Tehran, Iran. ghaem_amir@yahoo.com.
authors.forename: Amir
authors.initials: A
authors.lastname: Ghaemi
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003711:Demyelinating Diseases / Q000150:complications / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology* / Q000628:therapy*; D005260:Female; D056747:Immunomodulation / Q000187:drug effects*; D007249:Inflammation / Q000150:complications / Q000473:pathology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008810:Mice, Inbred C57BL; D020123:Sirolimus / Q000494:pharmacology*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D020123:Sirolimus
keywords: Cytokine; Multiple sclerosis; Neuropharmacology; Neuroprotection; Stem cells