Transplantation of placenta-derived mesenchymal stem cells in the EAE mouse model of MS.
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 traditional source of human MSCs, but human term placenta appears to be an excellent alternative because of its availability, 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 demonstrated that conditioned media from LPS-activated astrocytes stimulated PL-MSCs to express the gene TNF-α-stimulated gene/protein 6 (TSG-6). The same mRNA expression 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 assume that this effect is caused by reduction of the anti-inflammatory protein, TSG-6, of the inflammatory damage.
Neuroscience Laboratory, Felsenstein Medical Research Center-Tel Aviv University, Petah Tikva, Israel.
Yonit
Y
Fisher-Shoval
Yael
Y
Barhum
Ofer
O
Sadan
Shlomit
S
Yust-Katz
Tali
T
Ben-Zur
Nirit
N
Lev
Chen
C
Benkler
Moshe
M
Hod
Eldad
E
Melamed
Daniel
D
Offen
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology; D001921:Brain / Q000166:cytology; D002552:Cerebral Ventricles / Q000166:cytology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology / Q000628:therapy*; D005260:Female; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000473:pathology / Q000628:therapy*; D010920:Placenta / Q000166:cytology*; D011247:Pregnancy; D061251:Primary Cell Culture; D012720:Severity of Illness Index; D013116:Spinal Cord / Q000166:cytology; D013154:Spleen / Q000166:cytology; D014183:Transplantation, Heterologous