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Mater Sci Eng C Mater Biol Appl. 2017 Jul 1;76:934-943. doi: 10.1016/j.msec.2017.02.178. Epub 2017 Mar 21.

Combining NT3-overexpressing MSCs and PLGA microcarriers for brain tissue engineering: A potential tool for treatment of Parkinson's disease.

Author information

1
Tissue Engineering and Biomaterials Research Center, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran 14965/161, Iran; Faculty of Biomedical Engineering, Amirkabir University of Technology, Tehran 15875/4413, Iran.
2
Faculty of Biomedical Engineering, Amirkabir University of Technology, Tehran 15875/4413, Iran.
3
Tissue Engineering and Biomaterials Research Center, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran 14965/161, Iran.
4
Novel Drug Delivery Lab, Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
5
Tissue Engineering and Biomaterials Research Center, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran 14965/161, Iran. Electronic address: sfaghihi@nigeb.ac.ir.

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder that characterized by destruction of substantia nigrostriatal pathway due to the loss of dopaminergic (DA) neurons. Regardless of substantial efforts for treatment of PD in recent years, an effective therapeutic strategy is still missing. In a multidisciplinary approach, bone marrow derived mesenchymal stem cells (BMSCs) are genetically engineered to overexpress neurotrophin-3 (nt-3 gene) that protect central nervous system tissues and stimulates neuronal-like differentiation of BMSCs. Poly(lactic-co-glycolic acid) (PLGA) microcarriers are designed as an injectable scaffold and synthesized via double emulsion method. The surface of PLGA microcarriers are functionalized by collagen as a bioadhesive agent for improved cell attachment. The results demonstrate effective overexpression of NT-3. The expression of tyrosine hydroxylase (TH) in transfected BMSCs reveal that NT-3 promotes the intracellular signaling pathway of DA neuron differentiation. It is also shown that transfected BMSCs are successfully attached to the surface of microcarriers. The presence of dopamine in peripheral media of cell/microcarrier complex reveals that BMSCs are successfully differentiated into dopaminergic neuron. Our approach that sustains presence of growth factor can be suggested as a novel complementary therapeutic strategy for treatment of Parkinson disease.

KEYWORDS:

DA neurons; Neurotrophin-3; PLGA microcarriers; Parkinson's disease; Regenerative medicine

PMID:
28482609
DOI:
10.1016/j.msec.2017.02.178
[Indexed for MEDLINE]

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