Intravenous administration of mesenchymal stem cells exerts therapeutic effects on parkinsonian model of rats: Focusing on neuroprotective effects of stromal cell-derived factor-1α

Feifei Wang, Takao Yasuhara, Tetsuro Shingo, Masahiro Kameda, Naoki Tajiri, Wen J. Yuan, Akihiko Kondo, Tomohito Kadota, Tanefumi Baba, Judith T. Tayra, Yoichiro Kikuchi, Yasuyuki Miyoshi, Isao Date

Research output: Contribution to journalArticle

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Abstract

Background: Mesenchymal stem cells (MSCs) are pluripotent stem cells derived from bone marrow with secretory functions of various neurotrophic factors. Stromal cell-derived factor-1α (SDF-1α) is also reported as one of chemokines released from MSCs. In this research, the therapeutic effects of MSCs through SDF-1α were explored. 6-hydroxydopamine (6-OHDA, 20 μg) was injected into the right striatum of female SD rats with subsequent administration of GFP-labeled MSCs, fibroblasts, (i.v., 1 × 107 cells, respectively) or PBS at 2 hours after 6-OHDA injection. All rats were evaluated behaviorally with cylinder test and amphetamine-induced rotation test for 1 month with consequent euthanasia for immunohistochemical evaluations. Additionally, to explore the underlying mechanisms, neuroprotective effects of SDF-1α were explored using 6-OHDA-exposed PC12 cells by using dopamine (DA) assay and TdT-mediated dUTP-biotin nick-end labeling (TUNEL) staining.Results: Rats receiving MSC transplantation significantly ameliorated behaviorally both in cylinder test and amphetamine-induced rotation test compared with the control groups. Correspondingly, rats with MSCs displayed significant preservation in the density of tyrosine hydroxylase (TH)-positive fibers in the striatum and the number of TH-positive neurons in the substantia nigra pars compacta (SNc) compared to that of control rats. In the in vitro study, SDF-1α treatment increased DA release and suppressed cell death induced by 6-OHDA administration compared with the control groups.Conclusions: Consequently, MSC transplantation might exert neuroprotection on 6-OHDA-exposed dopaminergic neurons at least partly through anti-apoptotic effects of SDF-1α. The results demonstrate the potentials of intravenous MSC administration for clinical applications, although further explorations are required.

Original languageEnglish
Article number52
JournalBMC Neuroscience
Volume11
DOIs
Publication statusPublished - Apr 26 2010

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Chemokine CXCL12
Oxidopamine
Neuroprotective Agents
Therapeutic Uses
Mesenchymal Stromal Cells
Intravenous Administration
Mesenchymal Stem Cell Transplantation
Tyrosine 3-Monooxygenase
Amphetamine
Dopamine
Pluripotent Stem Cells
Control Groups
Euthanasia
Dopaminergic Neurons
PC12 Cells
Nerve Growth Factors
Biotin
Chemokines
Cell Death
Fibroblasts

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neuroscience(all)

Cite this

Intravenous administration of mesenchymal stem cells exerts therapeutic effects on parkinsonian model of rats : Focusing on neuroprotective effects of stromal cell-derived factor-1α. / Wang, Feifei; Yasuhara, Takao; Shingo, Tetsuro; Kameda, Masahiro; Tajiri, Naoki; Yuan, Wen J.; Kondo, Akihiko; Kadota, Tomohito; Baba, Tanefumi; Tayra, Judith T.; Kikuchi, Yoichiro; Miyoshi, Yasuyuki; Date, Isao.

In: BMC Neuroscience, Vol. 11, 52, 26.04.2010.

Research output: Contribution to journalArticle

Wang, Feifei ; Yasuhara, Takao ; Shingo, Tetsuro ; Kameda, Masahiro ; Tajiri, Naoki ; Yuan, Wen J. ; Kondo, Akihiko ; Kadota, Tomohito ; Baba, Tanefumi ; Tayra, Judith T. ; Kikuchi, Yoichiro ; Miyoshi, Yasuyuki ; Date, Isao. / Intravenous administration of mesenchymal stem cells exerts therapeutic effects on parkinsonian model of rats : Focusing on neuroprotective effects of stromal cell-derived factor-1α. In: BMC Neuroscience. 2010 ; Vol. 11.
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abstract = "Background: Mesenchymal stem cells (MSCs) are pluripotent stem cells derived from bone marrow with secretory functions of various neurotrophic factors. Stromal cell-derived factor-1α (SDF-1α) is also reported as one of chemokines released from MSCs. In this research, the therapeutic effects of MSCs through SDF-1α were explored. 6-hydroxydopamine (6-OHDA, 20 μg) was injected into the right striatum of female SD rats with subsequent administration of GFP-labeled MSCs, fibroblasts, (i.v., 1 × 107 cells, respectively) or PBS at 2 hours after 6-OHDA injection. All rats were evaluated behaviorally with cylinder test and amphetamine-induced rotation test for 1 month with consequent euthanasia for immunohistochemical evaluations. Additionally, to explore the underlying mechanisms, neuroprotective effects of SDF-1α were explored using 6-OHDA-exposed PC12 cells by using dopamine (DA) assay and TdT-mediated dUTP-biotin nick-end labeling (TUNEL) staining.Results: Rats receiving MSC transplantation significantly ameliorated behaviorally both in cylinder test and amphetamine-induced rotation test compared with the control groups. Correspondingly, rats with MSCs displayed significant preservation in the density of tyrosine hydroxylase (TH)-positive fibers in the striatum and the number of TH-positive neurons in the substantia nigra pars compacta (SNc) compared to that of control rats. In the in vitro study, SDF-1α treatment increased DA release and suppressed cell death induced by 6-OHDA administration compared with the control groups.Conclusions: Consequently, MSC transplantation might exert neuroprotection on 6-OHDA-exposed dopaminergic neurons at least partly through anti-apoptotic effects of SDF-1α. The results demonstrate the potentials of intravenous MSC administration for clinical applications, although further explorations are required.",
author = "Feifei Wang and Takao Yasuhara and Tetsuro Shingo and Masahiro Kameda and Naoki Tajiri and Yuan, {Wen J.} and Akihiko Kondo and Tomohito Kadota and Tanefumi Baba and Tayra, {Judith T.} and Yoichiro Kikuchi and Yasuyuki Miyoshi and Isao Date",
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T2 - Focusing on neuroprotective effects of stromal cell-derived factor-1α

AU - Wang, Feifei

AU - Yasuhara, Takao

AU - Shingo, Tetsuro

AU - Kameda, Masahiro

AU - Tajiri, Naoki

AU - Yuan, Wen J.

AU - Kondo, Akihiko

AU - Kadota, Tomohito

AU - Baba, Tanefumi

AU - Tayra, Judith T.

AU - Kikuchi, Yoichiro

AU - Miyoshi, Yasuyuki

AU - Date, Isao

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