Abstract

Stem cells have the potential as a regenerative therapy for cerebral ischemia by improving functional outcomes. However, cell transplantation has some limitations, including a low rate of the grafted cell survival. There is still a major challenge of promoting the harmonious symbiosis between grafted cells and the host. Acupuncture can effectively improve the functional outcome after cerebral ischemia. The present study evaluated the therapeutic effects and explored the mechanism of combined medial ganglionic eminence (MGE) neural progenitors differentiated from human embryonic stem cells (hESCs) with electroacupuncture (EA) in a bilateral common carotid artery occlusion (2VO) rat model. The results showed that EA could promote the survival of the grafted MGE neural progenitors differentiated from hESCs and alleviate learning and memory impairment in rats with cerebral ischemia. This may have partially resulted from inhibited expression of TNF-α and IL-1β and increased vascular endothelial growth factor (VEGF) expression and blood vessel density in the hippocampus. Our findings indicated that EA could promote the survival of the grafted MGE neural progenitors and enhance transplantation therapy's efficacy by promoting angiogenesis and inhibiting inflammation.

Highlights

  • Ischemic cerebrovascular disease is a leading cause of mortality and disability worldwide after heart disease and cancer, lacking effective therapeutic methods [1]

  • Human medial ganglionic eminence (MGE) Neural Progenitors Were Efficiently Generated from human embryonic stem cells (hESCs) In Vitro

  • Cognitive dysfunction in cerebral ischemia is related to cholinergic neuron loss in the hippocampus [33, 34]

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Summary

Introduction

Ischemic cerebrovascular disease is a leading cause of mortality and disability worldwide after heart disease and cancer, lacking effective therapeutic methods [1]. In addition to causing hemiplegia, aphasia, swallowing disorders, etc., cerebral ischemia can lead to a selective and delayed pyramidal neuronal death in the hippocampus and impair cognition function [2, 3]. Rapid vascular recanalization is a relatively effective therapy. Some patients cannot get timely access to effective treatment because the window for vascular recanalization is very short [4] and often results in intracranial hemorrhage [5]. Some drugs proven effective in animals could not reach desired therapeutic benefit in the clinic [6, 7]. Further investigation on effective treatments and interventions against cerebral ischemia is urgently needed

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