Protective effects of neurotrophic factor-secreting cells in a 6-OHDA rat model of parkinson disease

Ofer Sadan, Merav Bahat-Stromza, Yael Barhum, Yossef S. Levy, Anat Pisnevsky, Hagit Peretz, Avihay Bar Ilan, Shlomo Bulvik, Noam Shemesh, Dana Krepel, Yoram Cohen, Eldad Melamed, Daniel Offen

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1179-1190
Number of pages12
JournalStem Cells and Development
Volume18
Issue number8
DOIs
StatePublished - 1 Oct 2009

Fingerprint

Dive into the research topics of 'Protective effects of neurotrophic factor-secreting cells in a 6-OHDA rat model of parkinson disease'. Together they form a unique fingerprint.

Cite this