Journal
BRAIN RESEARCH
Volume 1431, Issue -, Pages 86-96Publisher
ELSEVIER
DOI: 10.1016/j.brainres.2011.10.038
Keywords
Parkinson's disease; Bone marrow-derived mesenchymal stem cell (MSC); Dopaminergic neuron; Noradrenergic neuron; Serotonergic neuron; Glial derived neurotrophic factor (GDNF)
Categories
Funding
- Burden Trust
- Ataxia UK
- Parkinson's UK
- John James Bristol Foundation
- Parkinson's UK [G-1005] Funding Source: researchfish
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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. (C) 2011 Elsevier B.V. All rights reserved.
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