Therapeutic Potential of a Combination of Electroacupuncture and TrkB-Expressing Mesenchymal Stem Cells for Ischemic Stroke.

Abstract:

: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.

journal_name

Mol Neurobiol

journal_title

Molecular neurobiology

authors

Ahn SM,Kim YR,Shin YI,Ha KT,Lee SY,Shin HK,Choi BT

doi

10.1007/s12035-018-1067-z

subject

Has Abstract

pub_date

2019-01-01 00:00:00

pages

157-173

issue

1

eissn

0893-7648

issn

1559-1182

pii

10.1007/s12035-018-1067-z

journal_volume

56

pub_type

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