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©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
Updates in the pathophysiological mechanisms of Parkinson’s disease: Emerging role of bone marrow mesenchymal stem cells
Hanaa H Ahmed, Ahmed M Salem, Hazem M Atta, Emad F Eskandar, Abdel Razik H Farrag, Mohamed A Ghazy, Neveen A Salem, Hadeer A Aglan
Hanaa H Ahmed, Emad F Eskandar, Hadeer A Aglan, Hormones Department, Medical Research Division, National Research Centre, Giza 12622, Egypt
Ahmed M Salem, Mohamed A Ghazy, Biochemistry Department, Faculty of Science, Ain Shams University, Cairo 1156, Egypt
Hazem M Atta, Clinical Biochemistry Department, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Hazem M Atta, Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Kasralainy, Cairo 11562, Egypt
Abdel Razik H Farrag, Pathology Department, Medical Research Division, National Research Centre, Giza 12622, Egypt
Neveen A Salem, Narcotics, Ergogenic aids and Poisons Department, Medical Research Division, National Research Centre, Giza 12622, Egypt
Author contributions: Ahmed HH designed and coordinated the research as well as wrote the paper; Salem AM analyzed the data; Atta HM performed the isolation and preparation steps of bone marrow mesenchymal stem cells from rats; Eskandar EF participated in the designation of the research; Farrag AH performed the immunohistochemical examination and histopathological investigations; Ghazy MA performed the molecular investigations; Salem NA and Aglan HA participated in the induction of Parkinson’s disease in rats and treatment as well as performed the biochemical measurements.
Institutional review board statement: The study was reviewed and approved by the National Research Centre Institutional Review Board.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the National Research Centre, protocol number: (09-200).
Conflict-of-interest statement: The authors declared no conflict of interest.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at hanaaomr@yahoo.com.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Hanaa H Ahmed, PhD, Professor of Biochemistry, Hormones Department, Medical Research Division, National Research Centre, 33 El-Bohouth Street, Dokki, Giza 12622, Egypt.
hanaaomr@yahoo.com
Telephone: +20-2-33335966 Fax: +20-2-33370931
Received: September 12, 2015
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.
