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Meta-Analysis
. 2022 Sep 5;13(1):452.
doi: 10.1186/s13287-022-03158-7.

Efficacy of stem cell therapy in animal models of intracerebral hemorrhage: an updated meta-analysis

Affiliations
Meta-Analysis

Efficacy of stem cell therapy in animal models of intracerebral hemorrhage: an updated meta-analysis

Chenchen Li et al. Stem Cell Res Ther. .

Abstract

Background: Multiple studies have reported that stem cell therapy has beneficial effects in animal models of intracerebral hemorrhage (ICH). However, this finding remains inconclusive. This study was performed to systematically determine the effect size of stem cell therapy in ICH animal models by pooling and analyzing data from newly published studies.

Methods: A literature search identified studies of stem cells in animal models of ICH. We searched mainstream databases from inception to November, 2021. And pooled effect size of stem cells was determined for diversified neurobehavioral scales and structural endpoints using random effects models.

Results: The median quality score of 62 included studies was 5.32. Our results revealed an overall positive effect of stem cell therapy. More specifically, the SMD was - 2.27 for mNSS, - 2.14 for rotarod test, - 2.06 for MLPT, - 1.33 for cylinder test, - 1.95 for corner turn test, - 1.42 for tissue loss, and - 1.86 for brain water content. For mNSS, classifying comparisons by quality score showed significant differences in estimates of effect size (p = 0.013), and high-quality comparisons showed a better outcome (SMD = - 2.57) compared with low-quality comparisons (SMD = - 1.59). Besides, different delivery routes also showed a significant difference in the estimates of effect size for mNSS (p = 0.002), and the intraperitoneal route showed the best outcome (SMD = - 4.63). For tissue loss, the autologous blood-induced ICH model showed a better outcome (SMD = - 1.84) compared with the collagenase-induced ICH model (SMD = - 0.94, p = 0.035). Additionally, stem cell therapy initiated within 8 h post-ICH showed the greatest efficacy on tissue loss reduction, followed by initiated with 24 h post-ICH. Finally, stem cells with different sources and types showed similar beneficial effects for mNSS as well as tissue loss.

Conclusions: Our results suggested that stem cell therapy had remarkable benefits on ICH animals on both the functional and structural outcomes in animal models of ICH, with very large effect size. These findings support the utility of further studies to translate stem cells in the treatment of ICH in humans. Moreover, the results should be interpreted in the light of the limitations in experimental design and the methodological quality of the studies included in the meta-analysis.

Keywords: Animal models; ICH; Stem cells; Updated, meta-analysis.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flow diagram of literature search and study selection
Fig. 2
Fig. 2
Forest plot shows mean effect size and 95% CI for (A) mNSS, (B) rotarod test, (C) MLPT, (D) cylinder test, (E) corner turn test between stem cell therapies treatment group and control group. SMD standardized mean difference; mNSS: modified neurological severity score; MLPT: modified limb placement test
Fig. 3
Fig. 3
Forest plot shows mean effect size and 95% CI for (A) tissue loss, (B) brain water content between stem cell therapies treatment group and control group. SMD standardized mean difference
Fig. 4
Fig. 4
Funnel plots indicating possible publication bias for (A) mNSS (B) tissue loss, (C) brain water content. Open circles are included studies and black circles represent imputed studies from post hoc trim-and-fill analysis. mNSS: modified neurological severity score

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