PMID- 29682700 OWN - NLM STAT- MEDLINE DCOM- 20190401 LR - 20200225 IS - 1559-1182 (Electronic) IS - 0893-7648 (Linking) VI - 56 IP - 1 DP - 2019 Jan TI - Therapeutic Potential of a Combination of Electroacupuncture and TrkB-Expressing Mesenchymal Stem Cells for Ischemic Stroke. PG - 157-173 LID - 10.1007/s12035-018-1067-z [doi] AB - We prepared and grafted tropomyosin receptor kinase B (TrkB) gene-transfected mesenchymal stem cells (TrkB-MSCs) into the ischemic penumbra and investigated whether electroacupuncture (EA) treatment could promote functional recovery from ischemic stroke. For the behavioral test, TrkB-MSCs+EA resulted in significantly improved motor function compared to that obtained with MSCs+EA or TrkB-MSCs alone. At 30 days after middle cerebral artery occlusion (MCAO), the largest number of grafted MSCs was detected in the TrkB-MSC+EA group. Some differentiation into immature neuroblasts and astrocytes was detected; however, only a few mature neuron-like cells were found. Compared to other treatments, TrkB-MSCs+EA upregulated the expression of mature brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT4) and induced the activation of TrkB receptor and its transcription factor cAMP response element-binding protein (CREB). At 60 days after MCAO, EA highly promoted the differentiation of TrkB-MSCs into mature neuron-like cells compared to the effect in MSCs. A selective TrkB antagonist, ANA-12, reverted the effect of TrkB-MSCs+EA in motor function recovery and survival of grafted MSCs. Our results suggest that EA combined with grafted TrkB-MSCs promotes the expression of BDNF and NT4, induces the differentiation of TrkB-MSCs, and improves motor function. TrkB-MSCs could serve as effective therapeutic agents for ischemic stroke if used in combination with BDNF/NT4-inducing therapeutic approaches. FAU - Ahn, Sung Min AU - Ahn SM AD - Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan, 50612, Republic of Korea. FAU - Kim, Yu Ri AU - Kim YR AD - Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan, 50612, Republic of Korea. AD - Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, 50612, Republic of Korea. FAU - Shin, Yong-Il AU - Shin YI AD - Department of Rehabilitation Medicine, School of Medicine, Pusan National University, Yangsan, 50612, Republic of Korea. FAU - Ha, Ki Tae AU - Ha KT AD - Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan, 50612, Republic of Korea. AD - Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, 50612, Republic of Korea. AD - Graduate Training Program of Korean Medicine for Healthy-Aging, Pusan National University, Yangsan, 50612, Republic of Korea. FAU - Lee, Seo-Yeon AU - Lee SY AD - Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan, 50612, Republic of Korea. AD - Graduate Training Program of Korean Medicine for Healthy-Aging, Pusan National University, Yangsan, 50612, Republic of Korea. FAU - Shin, Hwa Kyoung AU - Shin HK AD - Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan, 50612, Republic of Korea. AD - Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, 50612, Republic of Korea. AD - Graduate Training Program of Korean Medicine for Healthy-Aging, Pusan National University, Yangsan, 50612, Republic of Korea. FAU - Choi, Byung Tae AU - Choi BT AUID- ORCID: 0000-0002-5965-4346 AD - Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan, 50612, Republic of Korea. choibt@pusan.ac.kr. AD - Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, 50612, Republic of Korea. choibt@pusan.ac.kr. AD - Graduate Training Program of Korean Medicine for Healthy-Aging, Pusan National University, Yangsan, 50612, Republic of Korea. choibt@pusan.ac.kr. LA - eng GR - 2014R1A5A2009936/National Research Foundation of Korea/ GR - 2015R1A2A2A03006712/National Research Foundation of Korea/ PT - Journal Article DEP - 20180422 PL - United States TA - Mol Neurobiol JT - Molecular neurobiology JID - 8900963 RN - 0 (ANA 12 compound) RN - 0 (Azepines) RN - 0 (Benzamides) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Nerve Growth Factors) RN - EC 2.7.10.1 (Receptor, trkB) RN - P658DCA9XD (neurotrophin 4) SB - IM MH - Animals MH - Astrocytes/drug effects/metabolism/pathology MH - Azepines/pharmacology MH - Benzamides/pharmacology MH - Brain Ischemia/genetics/pathology/physiopathology/*therapy MH - Brain-Derived Neurotrophic Factor/genetics/metabolism MH - Cell Differentiation/drug effects MH - Cell Survival/drug effects MH - Combined Modality Therapy MH - *Electroacupuncture MH - Gene Expression Regulation/drug effects MH - Male MH - *Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/cytology/drug effects/*metabolism MH - Mice, Inbred C57BL MH - Motor Activity/drug effects MH - Nerve Growth Factors/genetics/metabolism MH - Neurons/drug effects/metabolism/pathology MH - Receptor, trkB/*metabolism MH - Signal Transduction/drug effects MH - Stroke/genetics/pathology/physiopathology/*therapy OTO - NOTNLM OT - Brain-derived neurotrophic factor OT - Electroacupuncture OT - Ischemic stroke OT - Mesenchymal stem cells OT - Neurotrophin-4 OT - Tropomyosin receptor kinase B EDAT- 2018/04/24 06:00 MHDA- 2019/04/02 06:00 CRDT- 2018/04/24 06:00 PHST- 2017/12/04 00:00 [received] PHST- 2018/04/08 00:00 [accepted] PHST- 2018/04/24 06:00 [pubmed] PHST- 2019/04/02 06:00 [medline] PHST- 2018/04/24 06:00 [entrez] AID - 10.1007/s12035-018-1067-z [pii] AID - 10.1007/s12035-018-1067-z [doi] PST - ppublish SO - Mol Neurobiol. 2019 Jan;56(1):157-173. doi: 10.1007/s12035-018-1067-z. Epub 2018 Apr 22.