Meta-Analysis
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Oct 26, 2019; 11(10): 891-903
Published online Oct 26, 2019. doi: 10.4252/wjsc.v11.i10.891
Stem cell treatment and cerebral palsy: Systemic review and meta-analysis
Simone Eggenberger, Céline Boucard, Andreina Schoeberlein, Raphael Guzman, Andreas Limacher, Daniel Surbek, Martin Mueller
Simone Eggenberger, Daniel Surbek, Martin Mueller, Department of Obstetrics and Gynaecology, Inselspital, University Hospital Bern, Bern 3010, Switzerland
Céline Boucard, Andreina Schoeberlein, Department for BioMedical Research, University of Bern, Bern 3008, Switzerland
Raphael Guzman, Department of Neurosurgery, University Hospital of Basel, Basel 4056, Switzerland
Andreas Limacher, CTU Bern, University of Bern, Bern 3012, Switzerland
Author contributions: Eggenberger S and Mueller M drafted and wrote the manuscript; Limacher A performed the statistical analysis; Guzman R, Boucard C, Schoeberlein A, Limacher A and Surbek D revised and provided critical and important intellectual content; all authors have given final approval of the version to be published.
Conflict-of-interest statement: The authors deny any conflict of interest.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Martin Mueller, MD, PhD, Senior Consultant, Department of Obstetrics and Gynaecology, Inselspital, University Hospital Bern, Friedbühlstrasse 19, Bern 3010, Switzerland. martin.mueller@insel.ch
Telephone: +41-31-6321125 Fax: +41-31-6321128
Received: March 12, 2019
Peer-review started: March 15, 2019
First decision: June 3, 2019
Revised: June 12, 2019
Accepted: August 20, 2019
Article in press: August 20, 2019
Published online: October 26, 2019
Processing time: 224 Days and 23.8 Hours
Abstract
BACKGROUND

Perinatal complications may result in life-long morbidities, among which cerebral palsy (CP) is the most severe motor disability. Once developed, CP is a non-progressive disease with a prevalence of 1-2 per 1000 live births in developed countries. It demands an extensive and multidisciplinary care. Therefore, it is a challenge for our health system and a burden for patients and their families. Recently, stem cell therapy emerged as a promising treatment option and raised hope in patients and their families.

AIM

The aim is to evaluate the efficacy and safety of stem cell treatment in children with CP using a systematic review and meta-analysis

METHODS

We performed a systematic literature search on PubMed and EMBASE to find randomized controlled clinical trials (RCT) investigating the effect of stem cell transplantation in children with CP. After the review, we performed a random-effects meta-analysis focusing on the change in gross motor function, which was quantified using the gross motor function measure. We calculated the pooled standardized mean differences of the 6- and/or 12-mo-outcome by the method of Cohen. We quantified the heterogeneity using the I-squared measure.

RESULTS

We identified a total of 8 RCT for a qualitative review. From the initially selected trials, 5 met the criteria and were included in the meta-analysis. Patients’ population ranged from 0.5 up to 35 years (n = 282). We detected a significant improvement in the gross motor function with a pooled standard mean difference of 0.95 (95% confidence interval: 0.13-1.76) favoring the stem cell group and a high heterogeneity (I2 = 90.1%). Serious adverse events were rare and equally distributed among both intervention and control groups.

CONCLUSION

Stem cell therapy for CP compared with symptomatic standard care only, shows a significant positive effect on the gross motor function, although the magnitude of the improvement is limited. Short-term safety is present and further high-quality RCTs are needed.

Keywords: Cerebral palsy; Perinatal brain injury; Stem cells; Umbilical cord blood; Mesenchymal stem/stromal cells; Gross motor function; Meta-analysis

Core tip: Cerebral palsy is a severe motor disability resulting from perinatal complications. Recently, stem cell therapy emerged as a promising treatment option and raised hope in patients and their families. However, high-quality randomized clinical trials investigating the efficacy of stem cell therapy as a treatment for cerebral palsy are scarce. We included the small number of currently available trials in our meta-analysis. A slight but significantly positive effect on the gross motor function favoring the stem cell group can be seen.