29-06-08(19:01:25)

Authors:

Wang FF., Yasuhara T., Yuan W., Tajiri N., Kondo A., Kadota T., Baba T., Liang HB., Date I.

Institutions:

Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

Title of abstract : Administration of mesenchymal stem cells has neuroprotective effects through SDF-1 on parkinsonian model rats

Abstract text:

Introduction
Recent studies suggest that transplantation of mesenchymal stem cells (MSCs) might be helpful for Parkinson’s disease. We investigated the hypothesis that intravenous infusion of MSCs induced functional recovery in parkinsonian model rats with underlying mechanisms.
Material and methods
6-hydroxydopamine (6-OHDA, 20μg) was injected into the right striatum of female SD rats with subsequent administration of GFP-labeled MSCs, fibrobrasts, (i.v., 1×10^7cells, respectively) or vehicle at 2 hours after 6-OHDA lesioning. All rats were evaluated behaviorally with cylinder test and amphetamine-induced rotation test for 1 month with consequent euthanasia for immunohistochemical evaluations. Additionally, to explore the underlying mechanisms, neuroprotective effects of stromal cell-derived factor-1 (SDF-1), which was secreted from MSCs were explored using 6-OHDA-treated PC12 cells with dopamine assay and TUNEL staining
Results
Behaviorally rats with MSCs transplantation significantly ameliorated both in cylinder test and amphetamine-induced rotation test, compared with fibroblast or PBS group. Correspondingly, rat with MSCs showed a better preservation in the density of tyrosine hydroxylase (TH)-positive fibers in the striatum and the number of TH-positive neurons in the substantia nigra pars compacta. In in vitro study, SDF-1-treatment increased dopamine release and suppressed cell death of 6-OHDA-treated PC12 cells, compared with the control.
Conclusions
Consequently, MSCs might exert neuroprotection for 6-OHDA-treated dopaminergic neurons through possibly with anti-apoptotic effects of SDF-1. The results suggest the effectiveness of intravenous MSCs administration and thus, clinical application might be considered, although further explorations are required.


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