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Original Article
131 (
4
); 536-544
doi:
10.25259/IJMR_20101314_536

Transplantation of retinoic acid treated murine embryonic stem cells & behavioural deficit in Parkinsonian rats

Kurdistan Center for Cellular & Molecular Research, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
Department of Anatomy, Faculty of Medical Sciences, Tarbiat Modares University Tehran, Tehran, Iran
Department of Genetics, Faculty of Basic Sciences, Tarbiat Modarres University, Tehran, Iran

Reprint requests: Dr Fardin Fathi, Department of Anatomy, KDRC, School of Medical Sciences, Kurdistan University of Medical Sciences P.O. Box: 66177-13446, Sanandaj, Iran e-mail: farfath@yahoo.com

Licence
This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background & objectives:

Stem cell therapy has been considered as an ideal option for the treatment of Parkinson’s disease. Murine embryonic stem cells (mESCs)-derived dopaminergic (DA) neurons may substitute the degenerated neurons in the brain. In this study we generated highly enriched cultures of neural progenitors from mESCs and grafted them into the striatum of Parkinsonian rats to evaluate their ability to improve impaired function.

Methods:

An animal model was developed for Parkinson’s disease in rats, using 6- hydroxy dopamine. The animals were divided into two groups: (i) the control group treated with culture medium only, and (ii) the experimental group, which was treated with a murine ESC cell-line (CCE). Transplanted cells were labelled with bromodeoxyuridine (BrdU), exposed to retinoic acid and then engrafted within the striatum of the rat model.

Results:

Treated ES cells by retinoic acid were found to relieve apomorphine-induced asymmetric motor behaviour. Immunohistochemistry results revealed tyrosine hydroxlase immunoreactivity in engrafted cells 15 days after transplantation. Further, the ultrastructural examination along with cresyl violet staining confirmed that the cells gained neuronal and glial appearance.

Interpretation & conclusions:

Our data demonstrate that retinoic acid treatment and transplanting ESC cells to the lessioned brain can lead to the generation of putative dopaminergic neurons and functional recovery in parkinsonian rat model with.

Keywords

Embryonic stem cells
Parkinson’s disease
retinoic acid
transplantation

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