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Review
. 2021 Apr 14:15:628908.
doi: 10.3389/fncel.2021.628908. eCollection 2021.

Stem Cell-Based Therapy for Experimental Ischemic Stroke: A Preclinical Systematic Review

Xi-Le Zhang  1 , Xiao-Guang Zhang  1 , Yan-Ran Huang  1 , Yan-Yan Zheng  1 , Peng-Jie Ying  1 , Xiao-Jie Zhang  1 , Xiao Lu  1 , Yi-Jing Wang  1 , Guo-Qing Zheng  1
Affiliations
Review

Stem Cell-Based Therapy for Experimental Ischemic Stroke: A Preclinical Systematic Review

Xi-Le Zhang et al. Front Cell Neurosci. .

Abstract

Stem cell transplantation offers promise in the treatment of ischemic stroke. Here we utilized systematic review, meta-analysis, and meta-regression to study the biological effect of stem cell treatments in animal models of ischemic stroke. A total of 98 eligible publications were included by searching PubMed, EMBASE, and Web of Science from inception to August 1, 2020. There are about 141 comparisons, involving 5,200 animals, that examined the effect of stem cell transplantation on neurological function and infarct volume as primary outcome measures in animal models for stroke. Stem cell-based therapy can improve both neurological function (effect size, -3.37; 95% confidence interval, -3.83 to -2.90) and infarct volume (effect size, -11.37; 95% confidence interval, -12.89 to -9.85) compared with controls. These results suggest that stem cell therapy could improve neurological function deficits and infarct volume, exerting potential neuroprotective effect for experimental ischemic stroke, but further clinical studies are still needed.

Keywords: ischemic stroke; middle cerebral artery occlusion; neuroprotection; pre-clinical systematic review; stem cell-based therapy.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Flow diagram of the search process.
FIGURE 2
FIGURE 2
Summary of the data included in the meta-analysis of the use of stem cells to treat ischemic stroke with individual comparisons ranked according to their effect on neurological function.
FIGURE 3
FIGURE 3
Summary of the data included in the meta-analysis of the use of stem cells to treat ischemic stroke with individual comparisons ranked according to their effect on infarct volume.
FIGURE 4
FIGURE 4
The impact of study characteristics on the effect sizes aimed at rat. (A) Type of ischemia, (B) sex of animals, (C) anesthetic used, (D) donor species, (E) stem cell, (F) cell manipulations, (G) dose range, (H) time of administration, and (I) route of delivery.
FIGURE 5
FIGURE 5
The impact of study characteristics on the effect sizes aimed at rat. (A) Type of ischemia, (B) sex of animals, (C) anesthetic used, (D) donor species, (E) stem cell, (F) cell manipulations, (G) dose range, (H) time of administration, and (I) route of delivery.
FIGURE 6
FIGURE 6
The impact of study characteristics on the effect sizes of two species. (A) Type of ischemia, (B) species, (C) sex of animals, (D) anesthetic used, (E) donor species, (F) stem cell, (G) cell manipulations, (H) dose range, (I) time of administration, and (J) route of delivery.
FIGURE 7
FIGURE 7
The impact of study characteristics on the effect sizes of two species. (A) Type of ischemia, (B) species, (C) sex of animals, (D) anesthetic used, (E) donor species, (F) stem cell, (G) cell manipulations, (H) dose range, (I) time of administration, and (J) route of delivery.
FIGURE 8
FIGURE 8
The funnel plot of the effect of stem cell on neurological function (A) and infarct volume (B) after experimental ischemic stroke.
FIGURE 9
FIGURE 9
Egger test for the assessment of the statistical significance of publication bias of neurological function.
FIGURE 10
FIGURE 10
Egger test for the assessment of the statistical significance of publication bias of infarct volume.
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