title: 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.
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.
authors.affiliation: Department of Neurology, Institute of Clinical Neurosciences, School of Clinical Sciences, University of Bristol, BS161LE, UK. alan.whone@bristol.ac.uk
authors.forename: Alan L
authors.initials: AL
authors.lastname: Whone
authors.forename: Kevin
authors.initials: K
authors.lastname: Kemp
authors.forename: Mingzhu
authors.initials: M
authors.lastname: Sun
authors.forename: Alastair
authors.initials: A
authors.lastname: Wilkins
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Scolding
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004622:Embryo, Mammalian; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D058953:Neural Stem Cells / Q000187:drug effects* / Q000502:physiology*; D009569:Nitric Oxide / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D050480:Plasma Membrane Neurotransmitter Transport Proteins / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D013997:Time Factors
chemical_list: D002395:Catecholamines; D017077:Culture Media, Conditioned; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D050480:Plasma Membrane Neurotransmitter Transport Proteins; C079036:Slc6a17 protein, rat; D009569:Nitric Oxide; D012701:Serotonin