The effectiveness of various cytotherapeutic strategies for the treatment of ischemic stroke: a Bayesian network meta-analysis of randomized controlled trials.

Abstract

Cytotherapy is a potential treatment for ischemic stroke (IS) patients but lacks uniform procedures. We aimed to assess the impact of the time of intervention, cell type, dose, and route of administration on the clinical effects by network meta-analysis. We searched public electronic databases through July 7, 2019. Bayesian network meta-analyses were performed to compare differences among different cytotherapeutic strategies. Cytotherapy can significantly improve patients' activity of daily living according to the modified Rankin Scale (standard mean difference (SMD) - 0.81; 95% confidence interval (CI) - 1.58, - 0.03; p = 0.0417) and Barthel Index (SMD 0.67; 95% CI 0.05, 1.30; p = 0.036) results as well as improve neurological recovery (SMD - 0.93; 95% CI - 1.29, - 0.57; p < 0.001). Network meta-analysis showed that the intra-arterial injection of large amounts of mononuclear cells (NCs) or aldehyde dehydrogenase (ALDH)-positive cells was beneficial for improving patients' activity of daily living, while CD34+ cells through intracerebral injection had an advantage in the recovery of injured nerve function. Intravenous injection of mesenchymal stem cells (MSCs) or endothelial progenitor cells (EPCs) was beneficial in reducing mortality and serious adverse event (SAE) onset. In the subacute stage, the intra-arterial injection of NCs or ALDH cells improves patients' activity of daily living. Additionally, CD34+ cells through intracerebral injection had an advantage in the recovery of injured nerve function even in the chronic stage. Intravenous injection of MSCs or EPCs is a safety delivery route that can reduce mortality and SAE onset. However, further clinical studies are still needed to confirm these results.