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Synergic Effects of Rehabilitation and Intravenous Infusion of Mesenchymal Stem Cells After Stroke in Rats

Yuichi Sasaki, Masanori Sasaki, Yuko Kataoka-Sasaki, Masahito Nakazaki, Hiroshi Nagahama, Junpei Suzuki, Daiki Tateyama, Shinichi Oka, Takahiro Namioka, Ai Namioka, Rie Onodera, Takeshi Mikami, Masahiko Wanibuchi, Masafumi Kakizawa, Sumio Ishiai, Jeffery D. Kocsis, Osamu Honmou
DOI: 10.2522/ptj.20150504 Published 1 November 2016
Yuichi Sasaki
Y. Sasaki, PT, PhD, Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan, and Department of Rehabilitation, Sapporo Medical University School of Medicine.
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Masanori Sasaki
M. Sasaki, MD, PhD, Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, 060-8556, Japan; Department of Neurology, Yale University School of Medicine, New Haven, Connecticut; and Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System, West Haven, Connecticut.
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Yuko Kataoka-Sasaki
Y. Kataoka-Sasaki, MD, PhD, Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine.
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Masahito Nakazaki
M. Nakazaki, MD, Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine.
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Hiroshi Nagahama
H. Nagahama, RT, Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine.
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Junpei Suzuki
J. Suzuki, PhD, Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine.
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Daiki Tateyama
D. Tateyama, BS, Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine.
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Shinichi Oka
S. Oka, MD, PhD, Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine.
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Takahiro Namioka
T. Namioka, MD, Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine.
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Ai Namioka
A. Namioka, MD, Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine.
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Rie Onodera
R. Onodera, PhD, Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine.
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Takeshi Mikami
T. Mikami, MD, PhD, Department of Neurosurgery, Sapporo Medical University School of Medicine.
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Masahiko Wanibuchi
M. Wanibuchi, MD, PhD, Department of Neurosurgery, Sapporo Medical University School of Medicine.
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Masafumi Kakizawa
M. Kakizawa, PT, Department of Rehabilitation, Sapporo Medical University School of Medicine.
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Sumio Ishiai
S. Ishiai, MD, PhD, Department of Rehabilitation, Sapporo Medical University School of Medicine.
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Jeffery D. Kocsis
J.D. Kocsis, PhD, Department of Neurology, Yale University School of Medicine, and Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System.
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Osamu Honmou
O. Honmou, MD, PhD, Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine; Department of Neurology, Yale University School of Medicine; and Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System.
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Figure 1.
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Figure 1.

Evaluation of the ischemic lesion volume with magnetic resonance imaging T2-weighted images (T2WI). Rat mesenchymal stem cells (MSCs) or vehicle (fresh Dulbecco's modified Eagle's medium) were intravenously infused 6 hours after middle cerebral artery occlusion (MCAO). The T2WI were obtained at days 1, 14, and 35 from the 4 experimental groups after MCAO induction: (A) group 1 (vehicle only), (B) group 2 (vehicle + exercise), (C) group 3 (MSCs only), and (D) group 4 (MSCs + exercise). Scale bar=5 mm. (E) A summary of lesion volume evaluated with T2WI were obtained 1, 14, and 35 days after MCAO in the 4 experimental groups. R=right, L=left. * P<.01.

Figure 2.
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Figure 2.

Synaptogenesis in the motor cortex in the infarcted hemisphere at layer III/IV was analyzed with a confocal microscopy. (A) Images were obtained from a boxed area in the motor cortex in infarcted hemisphere. (B) Infused green flourescent protein-mesenchymal stem cells GFP-MSCs (green) were present in the motor cortex in the infarcted hemisphere counterstained with DAPI (blue) 3 days after middle cerebral artery occlusion (n=3). Green flourescent protein (green) was observed in the cytoplasm, and DAPI is stained nucleus. No green cells were observed in these lesions after infusion of MSCs derived from wild-type Sprague-Dawley rats (inset). (C) Representative images of immunohisotochemical study for synaptophysin from intact animals (C-1), group 1 (vehicle only) (C-2), group 2 (vehicle + exercise) (C-3), group 3 (MSCs only) (C-4), and group 4 (MSCs + exercise) (C-5). (D) Quantitative analysis of density of synaptic puncta in the intact and 4 experimental groups. * P<.05. ** P<.01. Scale bar=10 μm.

Figure 5.
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Figure 5.

(A) The increased expression of synaptic marker protein correlated well with increased Limb Placement Test (LPT) scores, as illustrated by positive correlations between the density of synaptic puncta and LPT scores (r=.92, P<.01). (B) The increased thickness of corpus callosum (CC) correlated well with increased LPT scores, as illustrated by positive correlations between the thickness of CC and LPT scores (r=.78, P<.01). Group 1=vehicle only, group 2=vehicle + exercise, group 3=mesenchymal stem cells (MSCs) only, and group 4=MSCs + exercise.

Figure 4.
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Figure 4.

Assessment of behavioral function with the Limb Placement Test (LPT). One day after middle cerebral artery occlusion (MCAO), there was no statistical difference in LPT score among the 4 experimental groups. From day 14 on, groups 3 and 4 showed greater functional improvement compared with groups 1 and 2, but group 4 showed more improvement compared with group 3 at 35 days after MCAO. Group 1=vehicle only, group 2=vehicle + exercise, group 3=mesenchymal stem cells (MSCs) only, and group 4=MSCs + exercise. * P<.01.

Figure 3.
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Figure 3.

(A) Corpus callosum thickness was measured at the midline with T2-weighted images. (B) Quantitative results of corpus callosum thickness. Group 1=vehicle only, group 2=vehicle + exercise, group 3=mesenchymal stem cells (MSCs) only, and group 4=MSCs + exercise. * P<.01.

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Vol 96 Issue 11 Table of Contents
Physical Therapy: 96 (11)

Issue highlights

  • Physical Therapist Student Loan Debt
  • Exercise for Osteoarthritis of the Hip
  • Hospital-Based Outpatient Direct Access to Physical Therapist Services: Current Status in Wisconsin
  • Understanding the Relationship Between Physical Therapist Participation in Interdisciplinary Rounds and Hospital Readmission Rates: Preliminary Study
  • The 2015 Nepal Earthquake(s): Lessons Learned From the Disability and Rehabilitation Sector's Preparation for, and Response to, Natural Disasters
  • Icelandic Physical Therapists' Attitudes Toward Adoption of New Knowledge and Evidence-Based Practice: Cross-Sectional Web-Based Survey
  • Objective Gait and Balance Impairments Relate to Balance Confidence and Perceived Mobility in People With Parkinson Disease
  • Newly Identified Gait Patterns in Patients With Multiple Sclerosis May Be Related to Push-off Quality
  • Physical Rehabilitation Interventions for Post-mTBI Symptoms Lasting Greater Than 2 Weeks: Systematic Review
  • Fitkids Treadmill Test: Age- and Sex-Related Normative Values in Dutch Children and Adolescents
  • Joint-Specific Play Controller for Upper Extremity Therapy: Feasibility Study in Children With Wrist Impairment
  • Three Faces of Fragile X
  • Synergic Effects of Rehabilitation and Intravenous Infusion of Mesenchymal Stem Cells After Stroke in Rats
  • Structural Validity of the Mini-Balance Evaluation Systems Test (Mini-BESTest) in People With Mild to Moderate Parkinson Disease
  • Validity, Reliability, and Ability to Identify Fall Status of the Berg Balance Scale, BESTest, Mini-BESTest, and Brief-BESTest in Patients With COPD
  • Measurement Properties of the Quebec Back Pain Disability Scale in Patients With Nonspecific Low Back Pain: Systematic Review
  • Outcome Measure Recommendations From the Spinal Cord Injury EDGE Task Force
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Synergic Effects of Rehabilitation and Intravenous Infusion of Mesenchymal Stem Cells After Stroke in Rats
Yuichi Sasaki, Masanori Sasaki, Yuko Kataoka-Sasaki, Masahito Nakazaki, Hiroshi Nagahama, Junpei Suzuki, Daiki Tateyama, Shinichi Oka, Takahiro Namioka, Ai Namioka, Rie Onodera, Takeshi Mikami, Masahiko Wanibuchi, Masafumi Kakizawa, Sumio Ishiai, Jeffery D. Kocsis, Osamu Honmou
Physical Therapy Nov 2016, 96 (11) 1791-1798; DOI: 10.2522/ptj.20150504

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Synergic Effects of Rehabilitation and Intravenous Infusion of Mesenchymal Stem Cells After Stroke in Rats
Yuichi Sasaki, Masanori Sasaki, Yuko Kataoka-Sasaki, Masahito Nakazaki, Hiroshi Nagahama, Junpei Suzuki, Daiki Tateyama, Shinichi Oka, Takahiro Namioka, Ai Namioka, Rie Onodera, Takeshi Mikami, Masahiko Wanibuchi, Masafumi Kakizawa, Sumio Ishiai, Jeffery D. Kocsis, Osamu Honmou
Physical Therapy Nov 2016, 96 (11) 1791-1798; DOI: 10.2522/ptj.20150504
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  • Reliability and Validity of Force Platform Measures of Balance Impairment in Individuals With Parkinson Disease
  • Predictors of Reduced Frequency of Physical Activity 3 Months After Injury: Findings From the Prospective Outcomes of Injury Study
  • Effects of Locomotor Exercise Intensity on Gait Performance in Individuals With Incomplete Spinal Cord Injury
Show more Regenerative Rehabilitation and Genomics Special Series

Subjects

  • Geriatrics
    • Stroke (Geriatrics)
  • Intervention
    • Therapeutic Exercise
  • Special Series and Special Issues
    • Special Series on Regenerative Rehabilitation and Genomics
  • Neurology/Neuromuscular System
    • Stroke (Neurology)
    • Anatomy: Central Nervous System and Neuromuscular System

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