Protective effects of neurotrophic factor-secreting cells in a 6-OHDA rat model of Parkinson disease.
Stem cell-based therapy is a promising treatment for neurodegenerative diseases. In our laboratory, a novel protocol has been developed to induce bone marrow-derived mesenchymal stem cells (MSC) into neurotrophic factors- secreting cells (NTF-SC), thus combining stem cell-based therapy with the NTF-based neuroprotection. These cells produce and secrete factors such as brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor. Conditioned medium of the NTF-SC that was applied to a neuroblastoma cell line (SH-SY5Y) 1 h before exposure to the neurotoxin 6-hydroxydopamine (6-OHDA) demonstrated marked protection. An efficacy study was conducted on the 6-OHDA-induced lesion, a rat model of Parkinson's disease. The cells, either MSC or NTF-SC, were transplanted on the day of 6-OHDA administration and amphetamine-induced rotations were measured as a primary behavior index. We demonstrated that when transplanted posterior to the 6-OHDA lesion, the NTF-SC ameliorated amphetamine-induced rotations by 45%. HPLC analysis demonstrated that 6-OHDA induced dopamine depletion to a level of 21% compared to the untreated striatum. NTF-SC inhibited dopamine depletion to a level of 72% of the contralateral striatum. Moreover, an MRI study conducted with iron-labeled cells, followed by histological verification, revealed that the engrafted cells migrated toward the lesion. In a histological assessment, we found that the cells induced regeneration in the damaged striatal dopaminergic nerve terminal network. We therefore conclude that the induced MSC have a therapeutic potential for neurodegenerative processes and diseases, both by the NTFs secretion and by the migratory trait toward the diseased tissue.
Sadan
Ofer
O
Laboratory of Neurosciences, Felsenstein Medical Research Center, Department of Neurology, Rabin Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Bahat-Stromza
Merav
M
Barhum
Yael
Y
Levy
Yossef S
YS
Pisnevsky
Anat
A
Peretz
Hagit
H
Ilan
Avihay Bar
AB
Bulvik
Shlomo
S
Shemesh
Noam
N
Krepel
Dana
D
Cohen
Yoram
Y
Melamed
Eldad
E
Offen
Daniel
D
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000378:metabolism*; D016627:Oxidopamine; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation
D009414:Nerve Growth Factors; D016627:Oxidopamine