title: Intravenous mesenchymal stem cell administration exhibits therapeutic effects against 6-hydroxydopamine-induced dopaminergic neurodegeneration and glial activation in rats.
abstract: To explore a novel therapy against Parkinson's disease (PD), we evaluated the therapeutic effects of human bone marrow-derived mesenchymal stem cells (hBM-MSCs), pluripotent stromal cells with secretory potential of various neurotrophic and anti-inflammatory factors, in a hemi-parkinsonian rat model. The unilateral intrastriatal 6-hydroxydopamine (6-OHDA)-lesioned rats were injected hBM-MSCs (1.0 × 10(7)cells) or PBS intravenously 16 days after lesioning. Administration of hBM-MSCs inhibited methamphetamine-stimulated rotational behavior at 7, 14, 21 and 28 days after transplantation. Immunohistochemical analysis also showed that number of TH-positive neurons in the substantia nigra pars compacta was significantly preserved in hBM-MSCs-transplanted rats compared to sham-operated rats, whereas the immunoreactivity of ionized calcium binding adaptor molecule 1 was markedly inhibited. In this study, we demonstrated the therapeutic effects of intravenous hBM-MSCs administration in parkinsonian model rats presenting distinct parkinsonian phenotype at 16 days after 6-OHDA lesioning. The favorable findings raise the possibility that hBM-MSCs could be a novel therapeutic option to promote survival of dopaminergic neurons in PD.
authors.affiliation: Department of Neurology, School of Medicine, Sapporo Medical University, Sapporo, Japan.
authors.forename: Syuuichirou
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Department of Neurology, School of Medicine, Sapporo Medical University, Sapporo, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kawamata
authors.forename: Naotoshi
authors.initials: N
authors.lastname: Iwahara
authors.affiliation: Department of Neurology, School of Medicine, Sapporo Medical University, Sapporo, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Iwahara
authors.affiliation: Department of Neurology, School of Medicine, Sapporo Medical University, Sapporo, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Matsumura
authors.affiliation: Department of Neurology, School of Medicine, Sapporo Medical University, Sapporo, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Hisahara
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, USA.
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsushita
authors.affiliation: Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University, Sapporo, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Sasaki
authors.affiliation: Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University, Sapporo, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Honmou
authors.affiliation: Department of Neurology, School of Medicine, Sapporo Medical University, Sapporo, Japan. Electronic address: shimoha@sapmed.ac.jp.
authors.forename: Shun
authors.initials: S
authors.lastname: Shimohama
mesh_terms: D000818:Animals; D059290:Dopaminergic Neurons / Q000473:pathology*; D005260:Female; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D008694:Methamphetamine / Q000494:pharmacology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology / Q000628:therapy; D009457:Neuroglia / Q000378:metabolism*; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D017207:Rats, Sprague-Dawley; D013239:Stereotyped Behavior / Q000187:drug effects; D013378:Substantia Nigra / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D008694:Methamphetamine; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase
keywords: 6-Hydroxydopamine; Anti-inflammatory; Mesenchymal stem cell; Neuroprotection; Parkinson's disease