Margaret L Jackson1, Amit K Srivastava2, Charles S Cox2. 1. Department of Pediatric Surgery, University of Texas Health Sciences Center at Houston, Houston, Texas. Electronic address: margaret.l.jackson@uth.tmc.edu. 2. Department of Pediatric Surgery, University of Texas Health Sciences Center at Houston, Houston, Texas.
Abstract
BACKGROUND: No treatment is available to reverse injury associated with traumatic brain injury (TBI). Progenitor cell therapies show promise in both preclinical and clinical studies. We conducted a meta-analysis of preclinical studies using progenitor cells to treat TBI. METHODS: EMBASE, MEDLINE, Cochrane Review, Biosis, and Google Scholar were searched for articles using prespecified search strategies. Studies meeting inclusion criteria underwent data extraction. Analysis was performed using Review Manager 5.3 according to a fixed-effects model, and all studies underwent quality scoring. RESULTS: Of 430 abstracts identified, 38 met inclusion criteria and underwent analysis. Average quality score was 4.32 of 8 possible points. No study achieved a perfect score. Lesion volume (LV) and neurologic severity score (NSS) outcomes favored cell treatment with standard mean difference (SMD) of 0.86 (95% CI: 0.64-1.09) and 1.36 (95% CI: 1.11-1.60), respectively. Rotarod and Morris water maze outcomes also favored treatment with improvements in SMD of 0.34 (95% CI: 0.02-0.65) and 0.46 (95% CI: 0.17-74), respectively. Although LV and NSS were robust to publication bias assessments, rotarod and Morris water maze tests were not. Heterogeneity (I2) ranged from 74%-85% among the analyses, indicating a high amount of heterogeneity among studies. Precision as a function of quality score showed a statistically significant increase in the size of the confidence interval as quality improved. CONCLUSIONS: Our meta-analysis study reveals an overall positive effect of progenitor cell therapies on LV and NSS with a trend toward improved motor function and spatial learning in different TBI animal models.
BACKGROUND: No treatment is available to reverse injury associated with traumatic brain injury (TBI). Progenitor cell therapies show promise in both preclinical and clinical studies. We conducted a meta-analysis of preclinical studies using progenitor cells to treat TBI. METHODS: EMBASE, MEDLINE, Cochrane Review, Biosis, and Google Scholar were searched for articles using prespecified search strategies. Studies meeting inclusion criteria underwent data extraction. Analysis was performed using Review Manager 5.3 according to a fixed-effects model, and all studies underwent quality scoring. RESULTS: Of 430 abstracts identified, 38 met inclusion criteria and underwent analysis. Average quality score was 4.32 of 8 possible points. No study achieved a perfect score. Lesion volume (LV) and neurologic severity score (NSS) outcomes favored cell treatment with standard mean difference (SMD) of 0.86 (95% CI: 0.64-1.09) and 1.36 (95% CI: 1.11-1.60), respectively. Rotarod and Morris water maze outcomes also favored treatment with improvements in SMD of 0.34 (95% CI: 0.02-0.65) and 0.46 (95% CI: 0.17-74), respectively. Although LV and NSS were robust to publication bias assessments, rotarod and Morris water maze tests were not. Heterogeneity (I2) ranged from 74%-85% among the analyses, indicating a high amount of heterogeneity among studies. Precision as a function of quality score showed a statistically significant increase in the size of the confidence interval as quality improved. CONCLUSIONS: Our meta-analysis study reveals an overall positive effect of progenitor cell therapies on LV and NSS with a trend toward improved motor function and spatial learning in different TBI animal models.
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