Preconditioning Strategies to Enhance Neural Stem Cell-Based Therapy for Ischemic Stroke

Transplantation of neural stem cells (NSCs) has been proposed as an alternative novel therapy to replace damaged neural circuitry after ischemic stroke onset. Nonetheless, albeit the potential of these cells for stroke therapy, many critical challenges are yet to be overcome to reach clinical applic...

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Main Authors: Farah Amna Othman, Suat Cheng Tan
Format: Article
Language:English
Published: MDPI AG 2020-11-01
Series:Brain Sciences
Subjects:
Online Access:https://www.mdpi.com/2076-3425/10/11/893
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author Farah Amna Othman
Suat Cheng Tan
author_facet Farah Amna Othman
Suat Cheng Tan
author_sort Farah Amna Othman
collection DOAJ
description Transplantation of neural stem cells (NSCs) has been proposed as an alternative novel therapy to replace damaged neural circuitry after ischemic stroke onset. Nonetheless, albeit the potential of these cells for stroke therapy, many critical challenges are yet to be overcome to reach clinical applications. The major limitation of the NSC-based therapy is its inability to retain most of the donor stem cells after grafting into an ischemic brain area which is lacking of essential oxygen and nutrients for the survival of transplanted cells. Low cell survival rate limits the capacity of NSCs to repair the injured area and this poses a much more difficult challenge to the NSC-based therapy for ischemic stroke. In order to enhance the survival of transplanted cells, several stem cell culture preconditioning strategies have been employed. For ischemic diseases, hypoxic preconditioning is the most commonly applied strategy since the last few decades. Now, the preconditioning strategies have been developed and expanded enormously throughout years of efforts. This review systematically presented studies searched from PubMed, ScienceDirect, Web of Science, Scopus and the Google Scholar database up to 31 March 2020 based on search words containing the following terms: “precondition” or “pretreatment” and “neural stem cell” and “ischemic stroke”. The searched data comprehensively reported seven major NSC preconditioning strategies including hypoxic condition, small drug molecules such as minocycline, doxycycline, interleukin-6, adjudin, sodium butyrate and nicorandil, as well as electrical stimulation using conductive polymer for ischemic stroke treatment. We discussed therapeutic benefits gained from these preconditioned NSC for in vitro and in vivo stroke studies and the detailed insights of the mechanisms underlying these preconditioning approaches. Nonetheless, we noticed that there was a scarcity of evidence on the efficacy of these preconditioned NSCs in human clinical studies, therefore, it is still too early to draw a definitive conclusion on the efficacy and safety of this active compound for patient usage. Thus, we suggest for more in-depth clinical investigations of this cell-based therapy to develop into more conscientious and judicious evidence-based therapy for clinical application in the future.
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spelling doaj.art-8d1e2cb04c5d45b18975997e532e59a42023-11-20T21:55:57ZengMDPI AGBrain Sciences2076-34252020-11-01101189310.3390/brainsci10110893Preconditioning Strategies to Enhance Neural Stem Cell-Based Therapy for Ischemic StrokeFarah Amna Othman0Suat Cheng Tan1School of Health Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, MalaysiaSchool of Health Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, MalaysiaTransplantation of neural stem cells (NSCs) has been proposed as an alternative novel therapy to replace damaged neural circuitry after ischemic stroke onset. Nonetheless, albeit the potential of these cells for stroke therapy, many critical challenges are yet to be overcome to reach clinical applications. The major limitation of the NSC-based therapy is its inability to retain most of the donor stem cells after grafting into an ischemic brain area which is lacking of essential oxygen and nutrients for the survival of transplanted cells. Low cell survival rate limits the capacity of NSCs to repair the injured area and this poses a much more difficult challenge to the NSC-based therapy for ischemic stroke. In order to enhance the survival of transplanted cells, several stem cell culture preconditioning strategies have been employed. For ischemic diseases, hypoxic preconditioning is the most commonly applied strategy since the last few decades. Now, the preconditioning strategies have been developed and expanded enormously throughout years of efforts. This review systematically presented studies searched from PubMed, ScienceDirect, Web of Science, Scopus and the Google Scholar database up to 31 March 2020 based on search words containing the following terms: “precondition” or “pretreatment” and “neural stem cell” and “ischemic stroke”. The searched data comprehensively reported seven major NSC preconditioning strategies including hypoxic condition, small drug molecules such as minocycline, doxycycline, interleukin-6, adjudin, sodium butyrate and nicorandil, as well as electrical stimulation using conductive polymer for ischemic stroke treatment. We discussed therapeutic benefits gained from these preconditioned NSC for in vitro and in vivo stroke studies and the detailed insights of the mechanisms underlying these preconditioning approaches. Nonetheless, we noticed that there was a scarcity of evidence on the efficacy of these preconditioned NSCs in human clinical studies, therefore, it is still too early to draw a definitive conclusion on the efficacy and safety of this active compound for patient usage. Thus, we suggest for more in-depth clinical investigations of this cell-based therapy to develop into more conscientious and judicious evidence-based therapy for clinical application in the future.https://www.mdpi.com/2076-3425/10/11/893ischemic strokeneural stem cells (NSC)preconditioningcell transplantation
spellingShingle Farah Amna Othman
Suat Cheng Tan
Preconditioning Strategies to Enhance Neural Stem Cell-Based Therapy for Ischemic Stroke
Brain Sciences
ischemic stroke
neural stem cells (NSC)
preconditioning
cell transplantation
title Preconditioning Strategies to Enhance Neural Stem Cell-Based Therapy for Ischemic Stroke
title_full Preconditioning Strategies to Enhance Neural Stem Cell-Based Therapy for Ischemic Stroke
title_fullStr Preconditioning Strategies to Enhance Neural Stem Cell-Based Therapy for Ischemic Stroke
title_full_unstemmed Preconditioning Strategies to Enhance Neural Stem Cell-Based Therapy for Ischemic Stroke
title_short Preconditioning Strategies to Enhance Neural Stem Cell-Based Therapy for Ischemic Stroke
title_sort preconditioning strategies to enhance neural stem cell based therapy for ischemic stroke
topic ischemic stroke
neural stem cells (NSC)
preconditioning
cell transplantation
url https://www.mdpi.com/2076-3425/10/11/893
work_keys_str_mv AT farahamnaothman preconditioningstrategiestoenhanceneuralstemcellbasedtherapyforischemicstroke
AT suatchengtan preconditioningstrategiestoenhanceneuralstemcellbasedtherapyforischemicstroke