Protective effects of neurotrophic factors secreting cells in a 6OHDA rat model of Parkinson disease.
Stem Cells Dev. 2009 Feb 25;
Authors: Sadan O, Bahat-Stromza M, Barhum Y, Levy YS, Pisnevsky A, Peretz H, Bar Ilan A, Bulvik S, Shemesh N, Krepel D, Cohen Y, Melamed E, Offen D
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 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 and glial cell derived neurotrophic factor. Conditioned medium of the NTF-SC that was applied to a neuroblastoma cell line (SH-SY5Y) one hour 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 mesenchymal stem cells 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 a 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, 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 mesenchymal stem cells have a therapeutic potential for neurodegenerative processes and diseases, both by the NTFs secretion and by the migratory trait toward the diseased tissue.
PMID: 19243240 [PubMed - as supplied by publisher]