M. L. Jackson1, A. K. Srivastava1, C. S. Cox1 1McGovern Medical School,Department Of Pediatric Surgery,Houston, TX, USA
Introduction: There is currently no treatment available to reverse the primary injury associated with traumatic brain injury (TBI). Progenitor cell therapies have shown promise in both pre-clinical and clinical studies. We conducted a meta-analysis of pre-clinical studies using progenitor cells for the treatment of TBI.
Methods: PubMed, Cochrane Review, and Google Scholar were searched for articles using mesenchymal stromal/stem cells, umbilical cord derived stem cells/cord blood, placental stem cells, amniotic fluid derived stem cells, neural stem cells, and TBI. Inclusion criteria were (1) animal model of TBI with (2) administration of stem/progenitor cells, (3) and outcome measures that included either brain lesion volume (LV) assessment or rotarod (RR) motor function assessment, or both. Studies were excluded if they were not available in English, or if their design included combination with non-cellular therapies. Two investigators independently performed literature searches and screened abstracts. Discrepancies were decided by a third investigator. Studies meeting inclusion criteria underwent data extraction. Analysis was performed using Review Manager 5.3 according to a random-effects model; values are expressed as standard mean differences with 95% confidence interval (CI). All studies underwent quality scoring based on a combination of the recommendations for transparent reporting of basic science research from the NINDS, and a quality score that was developed for grading pre-clinical studies in stroke.
Results: Of 456 abstracts identified, 55 met inclusion criteria and underwent full text evaluation. Twelve studies evaluated RR testing as an outcome measure, and eight reported data that could be extracted. Nineteen studies evaluated LV, and sixteen reported data that could be extracted. Average quality score for the eight RR studies was 3.6 ± 0.7, and LV was 4.5 ± 1.8 out of 8 possible points. No study achieved a perfect score. LV outcomes favored cell treatment with standardized mean reduction of 1.43 (95%CI 0.85-2.00). RR outcomes showed a trend towards standard mean improvement of 0.59 which was not statistically significant (95%CI -0.20-1.37). Heterogeneity (I2) was 84% for LV analysis and 74% for RR analysis, indicating a high amount of heterogeneity among the studies compared.
Conclusions: Our meta-analysis evaluates both histological and functional outcome of progenitor cell therapies for TBI, and reports that despite heterogeneity among the studies there is a benefit in lesion volume reduction, and a trend towards overall improvement in motor function.
