title: Mesenchymal stem cells therapy exerts neuroprotection in a progressive animal model of Parkinson's disease.
abstract: Parkinson's disease is a common progressive neurodegenerative disorder caused by the loss of dopaminergic neurons in the substantia nigra. We investigated whether cell therapy with human mesenchymal stem cells (hMSCs) had a protective effect on progressive dopaminergic neuronal loss in vitro and in vivo. In primary mesencephalic cultures, hMSCs treatment significantly decreased MG-132-induced dopaminergic neuronal loss with a significant reduction of caspase-3 activity. In rats received systemic injection of MG-132, hMSCs treatment in MG-132-treated rats dramatically reduced the decline in the number of tyrosine hydroxylase (TH)-immunoreactive cells, showing an approximately 50% increase in the survival of TH-immunoreactive cells in the substantia nigra compared with the MG-132-treated group. Additionally, hMSC treatment significantly decreased OX-6 immunoreactivity and caspase-3 activity. Histological analysis showed that the number of NuMA-positive cells was 1.7% of total injected hMSCs and 35.7% of these cells were double-stained with NuMA and TH. Adhesive-removal test showed that hMSCs administration in MG-132-treated rats had a tendency to decrease in the mean removal time. This study demonstrates that hMSCs treatment had a protective effect on progressive loss of dopaminergic neurons induced by MG-132 in vitro and in vivo. Complex mechanisms mediated by trophic effects of hMSCs and differentiation of hMSCs into functional TH-immunoreactive neurons may work in the neuroprotective process.
authors.affiliation: Center for Neuroregeneration and Stem Cell Research, Ajou University School of Medicine, Suwon, South Korea.
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Park
authors.forename: Phil Hyu
authors.initials: PH
authors.lastname: Lee
authors.forename: Oh Young
authors.initials: OY
authors.lastname: Bang
authors.forename: Gwang
authors.initials: G
authors.lastname: Lee
authors.forename: Young Hwan
authors.initials: YH
authors.lastname: Ahn
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology; D002452:Cell Count; D016923:Cell Death / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D019610:Cytoprotection / Q000502:physiology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D020734:Parkinsonian Disorders / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery; D016896:Treatment Outcome; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; D009414:Nerve Growth Factors; D014446:Tyrosine 3-Monooxygenase; D053148:Caspase 3; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde; D004298:Dopamine