TY - JOUR
T1 - Therapeutic potential of mesenchymal stromal cells for hypoxic ischemic encephalopathy
T2 - A systematic review and meta-analysis of preclinical studies
AU - Archambault, Jamie
AU - Moreira, Alvaro
AU - McDaniel, Dawn
AU - Winter, Lauryn
AU - Sun, Lu Zhe
AU - Hornsby, Peter
N1 - Funding Information:
The project described was supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant KL2 TR001118 to Alvaro Moreira. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. This study was also supported by The University of Texas Health San Antonio School of Medicine Clinical Investigator Kickstart Pilot Grant to Alvaro Moreira.
Publisher Copyright:
© 2017 Archambault et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2017/12
Y1 - 2017/12
N2 - Introduction Neonatal 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. Methods Adhering 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. Results A 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. Conclusions Overall, 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.
AB - Introduction Neonatal 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. Methods Adhering 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. Results A 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. Conclusions Overall, 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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U2 - 10.1371/journal.pone.0189895
DO - 10.1371/journal.pone.0189895
M3 - Review article
C2 - 29261798
AN - SCOPUS:85038927638
SN - 1932-6203
VL - 12
JO - PLoS One
JF - PLoS One
IS - 12
M1 - e0189895
ER -