Electrical Stimulation Enhances Migratory Ability of Transplanted Bone Marrow Stromal Cells in a Rodent Ischemic Stroke Model

Jun Morimoto, Takao Yasuhara, Masahiro Kameda, Michiari Umakoshi, Ittetsu Kin, Ken Kuwahara, Kyohei Kin, Mihoko Okazaki, Hayato Takeuchi, Tatsuya Sasaki, Atsuhiko Toyoshima, Naoki Tajiri, Takashi Agari, Cesario V. Borlongan, Isao Date

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background/Aims: Bone marrow stromal cells (BMSCs) transplantation is an important strategy for the treatment of ischemic stroke. Currently, there are no effective methods to guide BMSCs toward the targeted site. In this study, we investigated the effect of electrical stimulation on BMSCs migration in an ischemic model of rats. Methods: Adult male Wistar rats weighing 200 to 250 g received right middle cerebral artery occlusion (MCAO) for 90 minutes. BMSCs (2.5×105 cells/ 4 μl PBS) were stereotaxically injected into the left corpus callosum at 1 day after MCAO. After BMSCs injection, a plate electrode with a diameter of 3 mm connected to an implantable electrical stimulator was placed on the right frontal epidural space and a counter electrode was placed in the extra-cranial space. Electrical stimulation at preset current (100 μA) and frequency (100 Hz) was performed for two weeks. Behavioral tests were performed at 1, 4, 8, and 15 days after MCAO using the modified Neurological Severity Score (mNSS) and cylinder test. Rats were euthanized at 15 days after MCAO for evaluation of infarction area and the migration distance and area of BMSCs found in the brain tissue. After evaluating cell migration, we proceeded to explore the mechanisms guiding these observations. MCAO rats without BMSCs transplantation were stimulated with same current and frequency. At 1 and 2 weeks after MCAO, rats were euthanized to evaluate stromal cell-derived factor 1 alpha (SDF-1α) level of brain tissues in the bilateral cortex and striatum. Results: Behavioral tests at 4, 8, and 15 days after MCAO revealed that stimulation group displayed significant amelioration in mNSS and cylinder test compared to control group (p<0.05). Similarly, the infarction areas of stroke rats in stimulation group were significantly decreased compared to control group (p<0.05). Migration distance and area of transplanted BMSCs were significantly longer and wider respectively in stimulation group. An increased concentration gradient of SDF-1α in stimulation group accompanied this enhanced migration of transplanted cells. Conclusions: These results suggest that electrical stimulation enhances migratory ability of transplanted BMSCs in ischemic stroke model of rats. If we can direct the implanted BMSCs to the site of interest, it may lead to a greater therapeutic effect.

Original languageEnglish
Pages (from-to)57-68
Number of pages12
JournalCellular Physiology and Biochemistry
Volume46
Issue number1
DOIs
Publication statusPublished - Apr 1 2018

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Aptitude
Mesenchymal Stromal Cells
Electric Stimulation
Rodentia
Middle Cerebral Artery Infarction
Stroke
Cell Movement
Chemokine CXCL12
Bone Marrow Transplantation
Infarction
Electrodes
Epidural Space
Control Groups
Corpus Callosum
Brain
Therapeutic Uses
Wistar Rats
Injections

Keywords

  • BMSCs
  • Cerebral infarction
  • Electrical stimulation
  • Migration
  • Transplantation

ASJC Scopus subject areas

  • Physiology

Cite this

Electrical Stimulation Enhances Migratory Ability of Transplanted Bone Marrow Stromal Cells in a Rodent Ischemic Stroke Model. / Morimoto, Jun; Yasuhara, Takao; Kameda, Masahiro; Umakoshi, Michiari; Kin, Ittetsu; Kuwahara, Ken; Kin, Kyohei; Okazaki, Mihoko; Takeuchi, Hayato; Sasaki, Tatsuya; Toyoshima, Atsuhiko; Tajiri, Naoki; Agari, Takashi; Borlongan, Cesario V.; Date, Isao.

In: Cellular Physiology and Biochemistry, Vol. 46, No. 1, 01.04.2018, p. 57-68.

Research output: Contribution to journalArticle

Morimoto, J, Yasuhara, T, Kameda, M, Umakoshi, M, Kin, I, Kuwahara, K, Kin, K, Okazaki, M, Takeuchi, H, Sasaki, T, Toyoshima, A, Tajiri, N, Agari, T, Borlongan, CV & Date, I 2018, 'Electrical Stimulation Enhances Migratory Ability of Transplanted Bone Marrow Stromal Cells in a Rodent Ischemic Stroke Model', Cellular Physiology and Biochemistry, vol. 46, no. 1, pp. 57-68. https://doi.org/10.1159/000488409
Morimoto, Jun ; Yasuhara, Takao ; Kameda, Masahiro ; Umakoshi, Michiari ; Kin, Ittetsu ; Kuwahara, Ken ; Kin, Kyohei ; Okazaki, Mihoko ; Takeuchi, Hayato ; Sasaki, Tatsuya ; Toyoshima, Atsuhiko ; Tajiri, Naoki ; Agari, Takashi ; Borlongan, Cesario V. ; Date, Isao. / Electrical Stimulation Enhances Migratory Ability of Transplanted Bone Marrow Stromal Cells in a Rodent Ischemic Stroke Model. In: Cellular Physiology and Biochemistry. 2018 ; Vol. 46, No. 1. pp. 57-68.
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AU - Kuwahara, Ken

AU - Kin, Kyohei

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AU - Takeuchi, Hayato

AU - Sasaki, Tatsuya

AU - Toyoshima, Atsuhiko

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