Systematic Reviews
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World J Stem Cells. Dec 26, 2022; 14(12): 851-867
Published online Dec 26, 2022. doi: 10.4252/wjsc.v14.i12.851
Biomaterial application strategies to enhance stem cell-based therapy for ischemic stroke
Asmaa’ Mohd Satar, Farah Amna Othman, Suat Cheng Tan
Asmaa’ Mohd Satar, Farah Amna Othman, Suat Cheng Tan, School of Health Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kelantan 16150, Malaysia
Author contributions: Tan SC designed the research; Mohd Satar A and Othman FA performed the literature review and analysis; All authors contributed to writing of the paper and gave approval of the final version.
Supported by the Universiti Sains Malaysia Research University Individual Grant, No. 1001/PPSK/8012273.
Conflict-of-interest statement: All the authors declare having no conflicts of interest.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
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 NonCommercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Suat Cheng Tan, PhD, Lecturer, School of Health Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kelantan 16150, Malaysia. tansc@usm.my
Received: September 11, 2022
Peer-review started: September 11, 2022
First decision: October 20, 2022
Revised: October 29, 2022
Accepted: December 6, 2022
Article in press: December 6, 2022
Published online: December 26, 2022
Processing time: 100 Days and 23.1 Hours
Abstract
BACKGROUND

Ischemic stroke is a condition in which an occluded blood vessel interrupts blood flow to the brain and causes irreversible neuronal cell death. Transplantation of regenerative stem cells has been proposed as a novel therapy to restore damaged neural circuitry after ischemic stroke attack. However, limitations such as low cell survival rates after transplantation remain significant challenges to stem cell-based therapy for ischemic stroke in the clinical setting. In order to enhance the therapeutic efficacy of transplanted stem cells, several biomaterials have been developed to provide a supportable cellular microenvironment or functional modification on the stem cells to optimize their reparative roles in injured tissues or organs.

AIM

To discuss state-of-the-art functional biomaterials that could enhance the therapeutic potential of stem cell-based treatment for ischemic stroke and provide detailed insights into the mechanisms underlying these biomaterial approaches.

METHODS

The PubMed, Science Direct and Scopus literature databases were searched using the keywords of “biomaterial” and “ischemic stroke”. All topically-relevant articles were then screened to identify those with focused relevance to in vivo, in vitro and clinical studies related to “stem cells” OR “progenitor cells” OR “undifferentiated cells” published in English during the years of 2011 to 2022. The systematic search was conducted up to September 30, 2022.

RESULTS

A total of 19 articles matched all the inclusion criteria. The data contained within this collection of papers comprehensively represented 19 types of biomaterials applied on seven different types of stem/progenitor cells, namely mesenchymal stem cells, neural stem cells, induced pluripotent stem cells, neural progenitor cells, endothelial progenitor cells, neuroepithelial progenitor cells, and neuroblasts. The potential major benefits gained from the application of biomaterials in stem cell-based therapy were noted as induction of structural and functional modifications, increased stem cell retention rate in the hostile ischemic microenvironment, and promoting the secretion of important cytokines for reparative mechanisms.

CONCLUSION

Biomaterials have a relatively high potential for enhancing stem cell therapy. Nonetheless, there is a scarcity of evidence from human clinical studies for the efficacy of this bioengineered cell therapy, highlighting that it is still too early to draw a definitive conclusion on efficacy and safety for patient usage. Future in-depth clinical investigations are necessary to realize translation of this therapy into a more conscientious and judicious evidence-based therapy for clinical application.

Keywords: Biomaterial; Stroke; Stem/progenitor cell therapy; Tissue bioengineering; Combined treatment

Core Tip: Ischemic stroke is becoming a significant health issue globally. An increasing number of studies have proposed the applications of regenerative stem cells for the treatment of this neurodegenerative disease. We critically reviewed the literature on biomaterial application to enhance the therapeutic potential of stem/progenitor cell therapy for ischemic stroke. Despite the limited evidence collected to translate this evidence into clinical practice, it is postulated that application of stem cells as regenerative treatment for stroke is practicable and beneficial for stroke patients, especially those in the chronic phase of stroke which could not be cured by any other established means.