Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Oct 26, 2019; 11(10): 817-830
Published online Oct 26, 2019. doi: 10.4252/wjsc.v11.i10.817
Neural stem cell transplantation therapy for brain ischemic stroke: Review and perspectives
Gui-Long Zhang, Zhi-Han Zhu, Ye-Zhong Wang
Gui-Long Zhang, Ye-Zhong Wang, Department of Neurosurgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, Guangdong Province, China
Zhi-Han Zhu, Department of Neurosurgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
Author contributions: Zhang GL and Wang YZ conceived and designed the review; Zhang GL and Zhu ZH wrote the paper; Zhang GL and Wang YZ edited the manuscript.
Supported by the China Postdoctoral Science Foundation, No. 2019TQ0071.
Institutional animal care and use committee statement: This article does not contain any studies with human participants or animal experiments.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Ye-Zhong Wang, MD, PhD, Professor, Department of Neurosurgery, The Second Affiliated Hospital of Guangzhou Medical University, 250 Changgang, Haizhu District, Guangzhou 510260, Guangdong Province, China.
Telephone: +86-20-34152766
Received: June 11, 2019
Peer-review started: June 19, 2019
First decision: August 1, 2019
Revised: August 11, 2019
Accepted: September 11, 2019
Article in press: September 11, 2019
Published online: October 26, 2019

Brain ischemic stroke is one of the most common causes of death and disability, currently has no efficient therapeutic strategy in clinic. Due to irreversible functional neurons loss and neural tissue injury, stem cell transplantation may be the most promising treatment approach. Neural stem cells (NSCs) as the special type of stem cells only exist in the nervous system, can differentiate into neurons, astrocytes, and oligodendrocytes, and have the abilities to compensate insufficient endogenous nerve cells and improve the inflammatory microenvironment of cell survival. In this review, we focused on the important role of NSCs therapy for brain ischemic stroke, mainly introduced the methods of optimizing the therapeutic efficacy of NSC transplantation, such as transfection and overexpression of specific genes, pretreatment of NSCs with inflammatory factors, and co-transplantation with cytokines. Next, we discussed the potential problems of NSC transplantation which seriously limited their rapid clinical transformation and application. Finally, we expected a new research topic in the field of stem cell research. Based on the bystander effect, exosomes derived from NSCs can overcome many of the risks and difficulties associated with cell therapy. Thus, as natural seed resource of nervous system, NSCs-based cell-free treatment is a newly therapy strategy, will play more important role in treating ischemic stroke in the future.

Keywords: Ischemic stroke, Neural stem cells, Transplantation, Cytokines, Exosomes

Core tip: In this review we compiled the latest available research regarding the use of neural stem cell therapy for the treatment of brain ischemic stroke. We discussed the benefits and limitations of this type of therapy focusing on the current efforts to improve its safety and efficacy. Further, we described a novel and clinically relevant strategy for the treatment of ischemic stroke based on cell free treatment–exosomes.