Therapeutic efficacy of mesenchymal stromal cells and secretome in pulmonary arterial hypertension: A systematic review and meta-analysis.

Mesenchymal stromal cells (MSCs) and secretome are promising therapies for pulmonary arterial hypertension (PAH). This meta-analysis aimed to provide a precise estimate and compare the therapeutic efficacy of MSC and secretome in PAH. We searched six databases (CINAHL, Cochrane, Ovid Medline, PubMed, Science Direct and Scopus) until December 2018 using search terms related to MSCs, secretome and PAH. Twenty-three studies were included for the meta-analysis. The effect size of pulmonary hemodynamics and right ventricular hypertrophy markers was estimated using random effects model. MSCs and secretome significantly improved pulmonary hemodynamics and right ventricular hypertrophy compared to control. Comparison between MSCs and secretome indicate no significant difference in reducing right ventricular systolic pressure (RVSP) and medial wall thickening (MWT). However, treatment of PAH with secretome significantly improved mean pulmonary arterial pressure (mPAP) (p = 0.018) and right ventricular/left ventricular + septum (RV/LV+S) (p = 0.017) better than MSCs. Meta-regression shows that cell type (p = 0.034) is a predictor of MSCs to reduce RVSP in PAH. Similarly, the effect of secretome on MWT was significantly (p = 0.011) better at 4 weeks compared to 2 weeks of intervention. The overall risk of bias ranges from low to moderate; however, some of the essential elements required in reports of animal trials were not reported. There was evidence of publication bias for RV/LV+S and MWT, but not RVSP. This meta-analysis provides evidence of the therapeutic benefits of MSCs and secretome in PAH and the effect of secretome was similar or superior to MSCs.