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Meta-Analysis
. 2024 Jan;95(1):18-33.
doi: 10.1038/s41390-022-02208-3. Epub 2022 Jul 29.

Mesenchymal stem cell therapy in perinatal arterial ischemic stroke: systematic review of preclinical studies

Verena Lehnerer #  1 , Anna Roidl #  1 , Olga Romantsik  2 , Raphael Guzman  3   4 , Sven Wellmann  1 , Matteo Bruschettini  5
Affiliations
Meta-Analysis

Mesenchymal stem cell therapy in perinatal arterial ischemic stroke: systematic review of preclinical studies

Verena Lehnerer et al. Pediatr Res. 2024 Jan.

Abstract

Background: Perinatal arterial ischemic stroke (PAIS) is a neurologic disorder leading to long-term complications. Mesenchymal stem cells (MSCs) have emerged as a novel therapeutic agent. This systematic review aims to determine the effects of stem cell-based interventions for the treatment of PAIS in preclinical studies.

Methods: We included all controlled studies on MSCs in neonatal animals with PAIS. Functional outcome was the primary outcome. The literature search was performed in February 2021.

Results: In the 20 included studies, MSCs were most frequently delivered via intracerebral injection (n = 9), 3 days after the induction of PAIS (n = 8), at a dose ranging from 5 × 104 to 5 × 106 cells. The meta-analysis showed an improvement on the cylinder rearing test (MD: -10.62; 95% CI: -14.38 to -6.86) and on the water maze test (MD: 1.31 MD; 95% CI: 0.80 to 1.81) in animals treated with MSCs compared to the control group animals.

Conclusion: MSCs appear to improve sensorimotor and cognitive performance in PAIS-injured animals; however, the certainty of the evidence is low. Registration of the protocol of preclinical studies, appropriate sample size calculation, rigorous randomization, and reporting of the data on animal sex and survival are warranted. PROSPERO registration number: CRD42021239642.

Impact: This is the first systematic review and meta-analysis of preclinical studies investigating the effects of MSCs in an experimental model of PAIS. MSCs appear to improve sensorimotor and cognitive performance in PAIS-injured neonatal animals. The certainty of the evidence is low due to high or unclear risk of bias in most domains.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
PRISMA flowchart.
Fig. 2
Fig. 2. Effect of treatment with MSC compared to control (PAIS with no MSC) for cylinder rearing test at 10, 21, and 28 days after PAIS.
Difference in route of application and dose.
Fig. 3
Fig. 3. Effect of treatment with MSC compared to control (PAIS with no MSC) for water maze test.
Difference in route of application and dose.
See this image and copyright information in PMC

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