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 therapy significantly improves survival and right ventricular function in a rat model of PAH, while repeated dosing offers no added benefit. • MSCs suppress pulmonary arterial adventitial fibroblast activation and reduce extracellular matrix deposition, attenuating vascular remodeling. • The therapeutic mechanism involves the SOCS3/STAT3 signaling pathway, providing a molecular target for PAH treatment. • Optimal timing of MSC administration is critical; early intervention (day 1) is more effective than delayed or repeated regimens.