Transplantation of Placenta-Derived Mesenchymal Stem Cells in the EAE Mouse Model of MS Yonit Fisher-Shoval & Yael Barhum & Ofer Sadan & Shlomit Yust-Katz & Tali Ben-Zur & Nirit Lev & Chen Benkler & Moshe Hod & Eldad Melamed & Daniel Offen Received: 5 April 2012 / Accepted: 3 May 2012 # Springer Science+Business Media, LLC 2012 Abstract Stem cell-based regenerative medicine raises great hope for the treatment of multiple sclerosis (MS). Bone marrow-derived mesenchymal stem cells (BM-MSCs) are being tested in clinical trials. Bone marrow is the tradi- tional source of human MSCs, but human term placenta appears to be an excellent alternative because of its avail- ability, without ethical issues. In this study, the therapeutic effect of human placental MSCs (PL-MSCs) was evaluated in experimental autoimmune encephalomyelitis (EAE), the mice model of MS. EAE mice were transplanted intra- cerebrally with PL-MSCs or with the vehicle saline 5 or 10 days after first MOG injection. The mice were monitored for a month after therapy. A daily EAE score revealed a decrease in disease severity in the transplanted animals when compared to saline. Survival was significantly higher in the transplanted animals. In vitro experiments demon- strated that conditioned media from LPS-activated astro- cytes stimulated PL-MSCs to express the gene TNF-α- stimulated gene/protein 6 (TSG-6). The same mRNA ex- pression was obtained when PL-MSCs were exposed to TNF-α or IL1-β. These results demonstrate that PL-MSCs have a therapeutic effect in the EAE mice model. We as- sume that this effect is caused by reduction of the anti- inflammatory protein, TSG-6, of the inflammatory damage. Keywords Multiple sclerosis (MS) . Experimental autoimmune encephalomyelitis (EAE) . Human placenta- derived MSCs (PL-MSCs) . TNF-α-stimulated gene/protein 6 (TSG-6) Introduction Multiple sclerosis (MS) is an inflammatory, demyelinating, and neurodegenerative disease of the central nervous sys- tem. It is a chronic, relapsing remitting disease characterized by patchy perivenular inflammatory infiltrates in areas of demyelination and axonal loss (Noseworthy et al. 2000). MS is one of the most common causes of neurological disability affecting young adults. The common treatment for MS is based on immunomodulation, mostly interferon-β or glatiramer acetate (Hemmer et al. 2006). Although partially effective in symptomatic alleviation, the current immuno- modulating drugs and any other available treatments do not halt the ongoing progression of neurodegeneration. Experimental autoimmune encephalomyelitis (EAE) is the most common animal model for MS, via T cell- mediated inflammation-induced demyelination and axonal damage. The disease is generally induced by immunization with myelin antigens such as myelin oligodendrocyte gly- coprotein (MOG) or myelin basic protein (MBP) and adju- vant, resulting in a CD4+ T helper-1 cell response that attacks the myelinated areas of the CNS (Whitha et al. 1991). Previous reports have shown the potential of cell-based therapy for EAE through transplantation of oligodendrocytes S. Yust-Katz : N. Lev : E. Melamed Department of Neurology, Rabin Medical Center, Petah Tikva, Israel M. Hod Division of Maternal Fetal Medicine, Hospital for Women, Rabin Medical Center, Petah Tikva, Israel Y. Fisher-Shoval : Y. Barhum (*) : O. Sadan : S. Yust-Katz : T. Ben-Zur : N. Lev : C. Benkler : E. Melamed : D. Offen Neuroscience Laboratory, Felsenstein Medical Research Center-Tel Aviv University, Petah Tikva, Israel e-mail: yael.barhum@gmail.com J Mol Neurosci DOI 10.1007/s12031-012-9805-6