1. Human bone marrow mesenchymal stem cells protect catecholaminergic and serotonergic neuronal perikarya and transporter function from oxidative stress by the secretion of glial-derived neurotrophic factor.
- Author
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Whone AL, Kemp K, Sun M, Wilkins A, and Scolding NJ
- Subjects
- Analysis of Variance, Animals, Cell Survival drug effects, Culture Media, Conditioned pharmacology, Embryo, Mammalian, Female, Glial Cell Line-Derived Neurotrophic Factor pharmacology, Humans, Nerve Growth Factors metabolism, Nerve Tissue Proteins metabolism, Nitric Oxide pharmacology, Oxidative Stress drug effects, Plasma Membrane Neurotransmitter Transport Proteins metabolism, Pregnancy, Rats, Time Factors, Catecholamines metabolism, Glial Cell Line-Derived Neurotrophic Factor metabolism, Mesenchymal Stem Cells metabolism, Neural Stem Cells drug effects, Neural Stem Cells physiology, Serotonin metabolism
- Abstract
In neurodegenerative disorders, including Parkinson's disease (PD), the potential of mesenchymal stem cells (MSCs) to produce neurorestoration via trans-differentiation has garnered much interest. We believe, however, that the paracrine effects of MSCs may have greater utility. MSCs release neurotrophic factors, including glial derived neurotrophic factor (GDNF). The benefits conferred by MSC GDNF release could potentially apply to all degenerating monoaminergic fibre types, throughout the brains of patients with PD, rather than solely affording protection to the dopaminergic neurones of the nigro-striatal pathway alone. Using an in vitro approach, we have investigated the neuroprotective properties of unmodified human MSCs on rat catecholaminergic and serotonergic cell cultures exposed to the damaging effects of nitric oxide. We have shown that post oxidative and inflammatory stress, soluble factors produced by native human MSCs, requiring no direct cell-cell contact or genetic or other manipulation, confer protection not only of cultured monoaminergic perikarya, but also of monoamine neurotransmitter transporter function. Furthermore, we have confirmed that, in part, this MSC mediated neuroprotective effect is due to MSC GDNF release and that such protection is diminished when the action of GDNF is blocked. Trophic factor release may afford a way by which intravenously infused MSCs can offer protection to all of the dopaminergic, noradrenergic and serotonergic fibre types degenerating widely throughout the brains of patients with PD., (Copyright © 2011 Elsevier B.V. All rights reserved.)
- Published
- 2012
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