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

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.

• Authors: 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
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 46 Issue 1 Pg. 57-68 ( 2018) ISSN: 1421-9778 [Electronic] Germany
• PMID: 29587284 (Publication Type: Journal Article)
• Copyright: © 2018 The Author(s). Published by S. Karger AG, Basel.

Chemical References

• CXCL12 protein, rat
• Chemokine CXCL12
• Cxcr4 protein, rat
• Receptors, CXCR4

Topics

• Animals
• Behavior, Animal
• Body Weight
• Bone Marrow Cells (cytology)
• Brain (pathology)
• Brain Ischemia (etiology)
• Cell Movement
• Cells, Cultured
• Chemokine CXCL12 (analysis, metabolism)
• Electric Stimulation
• Enzyme-Linked Immunosorbent Assay
• Infarction, Middle Cerebral Artery (complications)
• Male
• Mesenchymal Stem Cell Transplantation
• Mesenchymal Stem Cells (cytology)
• Rats
• Rats, Wistar
• Receptors, CXCR4 (metabolism)
• Stroke (pathology, prevention & control)