Mesenchymal stromal cells alleviate pulmonary arterial hypertension by suppressing pulmonary arterial adventitial fibroblast activation and extracellular matrix remodeling via the SOCS3/STAT3 pathway

• Early single-dose MSC administration (day 1 post-MCT) significantly improves survival and attenuates pulmonary vascular remodeling in a rat PAH model, whereas repeated dosing offers no additional benefit. • MSCs suppress pulmonary arterial adventitial fibroblast (PAAF) activation and reduce extracellular matrix (ECM) protein production both in vivo and in vitro. • The anti-fibrotic effect of MSCs is mediated through upregulation of SOCS3 and consequent inhibition of STAT3 phosphorylation. • Optimal timing of MSC therapy is critical; early intervention is more effective than delayed administration in reversing PAH progression.