Safety, efficacy and biomarkers analysis of mesenchymal stromal cells therapy in ARDS: a systematic review and meta-analysis based on phase I and II RCTs.

BACKGROUND: Mesenchymal stromal cells (MSCs) therapy for acute respiratory distress syndrome (ARDS) is an emerging treatment, but most of the current trials of MSCs stay in the animal experimental stage, and the safety and efficacy of MSCs in clinical application are not clear. We aimed to analyze the safety, efficacy and biomarkers of mesenchymal stromal cells in the treatment of ARDS. METHODS: For this systematic review and meta-analysis, we searched PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of science, CNKI, VIP and Wan Fang data, studies published between database inception and Mar 17, 2022. All randomized controlled trials (RCT) of stem cell interventions for ARDS were included, without language or date restrictions. We did separate meta-analyses for mortality, subjects with adverse events (AEs) and subjects with serious adverse events (SAEs). Since the trials data are dichotomous outcomes, the odds ratio (OR) is adopted for meta-analysis. The quality of the evidence was assessed with the Cochrane risk of bias tool. FINDINGS: In total, 5 trials involving 171 patients with ARDS were included in this meta-analysis. A total of 99 individuals were randomly assigned to receive MSCs treatment, and 72 were randomly assigned to receive placebo treatment. Treatment with MSCs appeared to increase the occurrence of adverse events, but this result was not statistically significant (OR, 1.58; 95%CI, 0.64-3.91; P = 0.32). The occurrence of serious adverse events was lower in the MSCs group than in the placebo group (OR, 0.57; 95%CI, 0.14-2.32; P = 0.43); there seems to be no significant difference between the two groups in terms of 28 days mortality (OR, 0.93; 95%CI, 0.45-1.89); oxygenation index and biomarkers showed a tendency to improve in treatment, but there was a lack of more statistically significant clinical evidence to support them. INTERPRETATION: Based on the current clinical trials, MSCs intervention has some safety for ARDS patients, but its effectiveness and predictive value of airspace biomarkers need to be determined by more large-scale, standard randomized controlled trials.

Simultaneous determination of six phenolic constituents of Danshen injection in rat plasma by LC-ESI-MS and its application to a pharmacokinetic study.

Salvianolic acid A, salvianolic acid B, danshensu, protocatechuic aldehyde, rosmarinic acid and lithospermic acid are the six major active constituents in Danshen injection. In this study, a rapid, sensitive and specific liquid chromatographic-electrospray ionization-mass spectrometry method for the simultaneous quantitative determination of these compounds in rat plasma was developed. After a single step of liquid-liquid extraction with ethyl acetate, they were eluted by a Hypersil C18 column (5 µm, i.d. 4.6 × 200 mm) within 4 min with a mobile phase consisting of acetonitrile and 0.1% formic acid water solution (35:65, v/v). The assay was linear in the concentration range of 0.05-10 µg mL(-1). Absolute recoveries were above 60%. The precisions and accuracies determined within three consecutive days were within acceptable limits. The method was successfully applied to a pharmacokinetic study in rats after an intravenous administration of Danshen injection.