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

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 x 10(4) to 5 x 10(6) 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.