• Jamie Archambault, Alvaro Moreira, Dawn McDaniel, Lauryn Winter, LuZhe Sun, and Peter Hornsby.
• Department of Pediatrics, Division of Neonatology, University of Texas Health-San Antonio, San Antonio, Texas, United States of America.
• Plos One. 2017 Jan 1; 12 (12): e0189895.

IntroductionNeonatal hypoxic ischemic encephalopathy (HIE) is a devastating neurologic condition with high mortality rates and long-term complications for surviving infants. Mesenchymal stem/stromal cells (MSCs) have emerged as novel therapeutic agents with promising results in experimental studies of HIE. The purpose of this study is to (a) methodically review the current preclinical literature describing MSC therapy in animal models of HIE, (b) quantify the effect size in regards to functional neurologic outcome, and (c) identify research gaps/limitations that should be addressed prior to future preclinical and clinical studies.MethodsAdhering to the Systematic Review Protocol for Animal Intervention Studies, a systematic search of English articles was performed. Eligible studies were identified and data regarding study characteristics and outcome measures was extracted. After quality assessment, meta-analysis and meta-regression were performed to generate random effect size using standardized mean difference (SMD). Funnel plots and Egger's tests were utilized to evaluate for the presence of publication bias.ResultsA total of 19 studies met inclusion in the current systematic review. Meta-analysis revealed that MSCs have a significant positive effect on neurobehavioral outcome following HIE injury. Sensorimotor function was improved by 2.25 SMD (95% CI; 2.04-2.46) in cylinder rearing and 2.97 SMD (95% CI; 2.56-3.38) in rotarod. Likewise, cognitive function was improved by 2.76 SMD (95% CI; 2.53-2.98) on the water maze and 2.97 SMD (95% CI; 2.58-3.35) in object recognition. Stratification demonstrated an increased effect size depending on various study characteristics.ConclusionsOverall, these results suggest a promising role for MSCs in preclinical studies of HIE. MSC treatment demonstrates improved functional outcomes that are encouraging for future translational studies. While risk of bias and heterogeneity limited the strength of our meta-analysis, our results are consistent with those seen in this field of research.

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