Published online Mar 26, 2016. doi: 10.4252/wjsc.v8.i3.106
Peer-review started: September 16, 2015
First decision: November 7, 2015
Revised: February 1, 2016
Accepted: February 23, 2016
Article in press: February 24, 2016
Published online: March 26, 2016
Processing time: 191 Days and 0.8 Hours
AIM: To explore the approaches exerted by mesenchymal stem cells (MSCs) to improve Parkinson’s disease (PD) pathophysiology.
METHODS: MSCs were harvested from bone marrow of femoral bones of male rats, grown and propagated in culture. Twenty four ovariectomized animals were classified into 3 groups: Group (1) was control, Groups (2) and (3) were subcutaneously administered with rotenone for 14 d after one month of ovariectomy for induction of PD. Then, Group (2) was left untreated, while Group (3) was treated with single intravenous dose of bone marrow derived MSCs (BM-MSCs). SRY gene was assessed by PCR in brain tissue of the female rats. Serum transforming growth factor beta-1 (TGF-β1), monocyte chemoattractant protein-1 (MCP-1) and brain derived neurotrophic factor (BDNF) levels were assayed by ELISA. Brain dopamine DA level was assayed fluorometrically, while brain tyrosine hydroxylase (TH) and nestin gene expression were detected by semi-quantitative real time PCR. Brain survivin expression was determined by immunohistochemical procedure. Histopathological investigation of brain tissues was also done.
RESULTS: BM-MSCs were able to home at the injured brains and elicited significant decrease in serum TGF-β1 (489.7 ± 13.0 vs 691.2 ± 8.0, P < 0.05) and MCP-1 (89.6 ± 2.0 vs 112.1 ± 1.9, P < 0.05) levels associated with significant increase in serum BDNF (3663 ± 17.8 vs 2905 ± 72.9, P < 0.05) and brain DA (874 ± 15.0 vs 599 ± 9.8, P < 0.05) levels as well as brain TH (1.18 ± 0.004 vs 0.54 ± 0.009, P < 0.05) and nestin (1.29 ± 0.005 vs 0.67 ± 0.006, P < 0.05) genes expression levels. In addition to, producing insignificant increase in the number of positive cells for survivin (293.2 ± 15.9 vs 271.5 ± 15.9, P > 0.05) expression. Finally, the brain sections showed intact histological structure of the striatum as a result of treatment with BM-MSCs.
CONCLUSION: The current study sheds light on the therapeutic potential of BM-MSCs against PD pathophysiology via multi-mechanistic actions.
Core tip: The current study was planned to clarify the mode of action of mesenchymal stem cells (MSCs) in targeting multiple systems implicated in the pathophysiology of Parkinson’s disease (PD) in the rat model. For this purpose, the MSCs were isolated from bone marrow (BM) of rat femur bone and PD was induced in ovariectomized rats by rotenone administration for 14 d. Our results provided clear evidences for the therapeutic role of BM-derived MSCs against PD pathophysiology through their immunomodulatory properties, anti-inflammatory and anti-apoptotic effects as well as neurotrophic and neurogenic potentials.