Efficacy of stem cell secretome in the treatment of traumatic brain injury: A systematic review and meta-analysis of preclinical studies.

Traumatic brain injury (TBI) remains a public health challenge and represents one of the major contributors to disability and mortality worldwide among all trauma-related injuries. This study aimed to determine a precise effect size of secretome intervention in TBI. We performed a systematic literature search through Cochrane, MEDLINE Complete, PubMed and Scopus databases for articles published until June 2021. The search terms used include cells OR stem cells OR mesenchymal stem cells AND secretome OR conditioned medium OR extracellular vesicles OR exosomes OR microvesicles AND traumatic brain injury OR head injury. Neurological deficits and neuroinflammation were the outcome measures assessed after the intervention. Thirty-one (31) studies involving mouse, rat and swine were enrolled for the meta-analysis. Secretome significantly improved structural and functional recovery when compared with control. The mean effect sizes were as follows: modified neurological severity score (mNSS) (-2.65, 95% CI: -3.42, -1.87, p < 0.00001), impact size (-3.02 mm, 95% CI: -4.97, -1.08, p = 0.002) and latency to platform (-17.20 s, 95% CI: -23.91, -10.50, p < 0.00001). Similarly, intervention with secretome reduced neuroinflammation after TBI. The results of meta-regression showed that the source of secretome, TBI models and duration of follow-up did not influence the mNSS. Furthermore, the methodological quality of the studies was moderate as shown by the risk of bias assessment. Publication bias was observed for the mNSS. This meta-analysis provides preclinical evidence of secretome intervention in TBI, suggesting that it can be explored as a therapeutic agent for TBI and other neurological disorders in humans.