Intracerebroventricular transplantation of human mesenchymal stem cells induced to secrete neurotrophic factors attenuates clinical symptoms in a mouse model of multiple sclerosis.
Stem cell-based therapy holds great potential for future treatment of multiple sclerosis (MS). Bone marrow mesenchymal stem cells (MSCs) were previously reported to ameliorate symptoms in mouse MS models (experimental autoimmune encephalomyelitis, EAE). In this study, we induced MSCs to differentiate in vitro into neurotrophic factor-producing cells (NTFCs). Our main goal was to examine the clinical use of NTFCs on EAE symptoms. The NTFCs and MSCs were transplanted intracerebroventricularly (ICV) to EAE mice. We found that NTFCs transplantations resulted in a delay of symptom onset and increased animal survival. Transplantation of MSCs also exerted a positive effect but to a lesser extent. In vitro analysis demonstrated the NTFCs' capacity to suppress mice immune cells and protect neuronal cells from oxidative insult. Our results indicate that NTFCs-transplanted ICV delay disease symptoms of EAE mice, possibly via neuroprotection and immunomodulation, and may serve as a possible treatment to MS.
Barhum
Yael
Y
Felsenstein Medical Research Center, Tel Aviv University, Sackler School of Medicine, Petach Tikva, 49100, Israel.
Gai-Castro
Sharon
S
Bahat-Stromza
Merav
M
Barzilay
Ran
R
Melamed
Eldad
E
Offen
Daniel
D
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D009103:Multiple Sclerosis / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D009414:Nerve Growth Factors / Q000378:metabolism*; D013601:T-Lymphocytes / Q000502:physiology
D017077:Culture Media, Conditioned; D009414:Nerve Growth Factors