PMID- 29587284 OWN - NLM STAT- MEDLINE DCOM- 20180625 LR - 20190212 IS - 1421-9778 (Electronic) IS - 1015-8987 (Linking) VI - 46 IP - 1 DP - 2018 TI - Electrical Stimulation Enhances Migratory Ability of Transplanted Bone Marrow Stromal Cells in a Rodent Ischemic Stroke Model. PG - 57-68 LID - 10.1159/000488409 [doi] AB - 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 (2.5x105 cells/ 4 microl 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 microA) 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-1alpha) 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-1alpha 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. CI - (c) 2018 The Author(s). Published by S. Karger AG, Basel. FAU - Morimoto, Jun AU - Morimoto J AD - Department of Neurological Surgery, Okayama University Graduate School of Medicine, Okayama, Japan. FAU - Yasuhara, Takao AU - Yasuhara T AD - Department of Neurological Surgery, Okayama University Graduate School of Medicine, Okayama, Japan. FAU - Kameda, Masahiro AU - Kameda M AD - Department of Neurological Surgery, Okayama University Graduate School of Medicine, Okayama, Japan. FAU - Umakoshi, Michiari AU - Umakoshi M AD - Department of Neurological Surgery, Okayama University Graduate School of Medicine, Okayama, Japan. FAU - Kin, Ittetsu AU - Kin I AD - Department of Neurological Surgery, Okayama University Graduate School of Medicine, Okayama, Japan. FAU - Kuwahara, Ken AU - Kuwahara K AD - Department of Neurological Surgery, Okayama University Graduate School of Medicine, Okayama, Japan. FAU - Kin, Kyohei AU - Kin K AD - Department of Neurological Surgery, Okayama University Graduate School of Medicine, Okayama, Japan. FAU - Okazaki, Mihoko AU - Okazaki M AD - Department of Neurological Surgery, Okayama University Graduate School of Medicine, Okayama, Japan. FAU - Takeuchi, Hayato AU - Takeuchi H AD - Department of Neurological Surgery, Okayama University Graduate School of Medicine, Okayama, Japan. FAU - Sasaki, Tatsuya AU - Sasaki T AD - Department of Neurological Surgery, Okayama University Graduate School of Medicine, Okayama, Japan. FAU - Toyoshima, Atsuhiko AU - Toyoshima A AD - Department of Neurological Surgery, Okayama University Graduate School of Medicine, Okayama, Japan. FAU - Tajiri, Naoki AU - Tajiri N AD - Department of Neurological Surgery, Okayama University Graduate School of Medicine, Okayama, Japan. AD - Department of Psychology, Graduate School of Psychology, Kibi International University 8 Iga-machi, Takahashi-city, Okayama, Japan. FAU - Agari, Takashi AU - Agari T AD - Department of Neurological Surgery, Okayama University Graduate School of Medicine, Okayama, Japan. FAU - Borlongan, Cesario V AU - Borlongan CV AD - Department of Neurosurgery, University of South Florida Morsani College of Medicine, Tampa, Florida, USA. FAU - Date, Isao AU - Date I AD - Department of Neurological Surgery, Okayama University Graduate School of Medicine, Okayama, Japan. LA - eng PT - Journal Article DEP - 20180320 PL - Germany TA - Cell Physiol Biochem JT - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology JID - 9113221 RN - 0 (CXCL12 protein, rat) RN - 0 (Chemokine CXCL12) RN - 0 (Cxcr4 protein, rat) RN - 0 (Receptors, CXCR4) SB - IM MH - Animals MH - Behavior, Animal MH - Body Weight MH - Bone Marrow Cells/cytology MH - Brain/pathology MH - Brain Ischemia/etiology MH - Cell Movement MH - Cells, Cultured MH - Chemokine CXCL12/analysis/metabolism MH - Electric Stimulation MH - Enzyme-Linked Immunosorbent Assay MH - Infarction, Middle Cerebral Artery/complications MH - Male MH - *Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/cytology MH - Rats MH - Rats, Wistar MH - Receptors, CXCR4/metabolism MH - Stroke/pathology/*prevention & control OTO - NOTNLM OT - BMSCs OT - Cerebral infarction OT - Electrical stimulation OT - Migration OT - Transplantation EDAT- 2018/03/28 06:00 MHDA- 2018/06/26 06:00 CRDT- 2018/03/28 06:00 PHST- 2017/08/22 00:00 [received] PHST- 2017/12/12 00:00 [accepted] PHST- 2018/03/28 06:00 [pubmed] PHST- 2018/06/26 06:00 [medline] PHST- 2018/03/28 06:00 [entrez] AID - 000488409 [pii] AID - 10.1159/000488409 [doi] PST - ppublish SO - Cell Physiol Biochem. 2018;46(1):57-68. doi: 10.1159/000488409. Epub 2018 Mar 20.