Persistence and proliferation of human mesenchymal stromal cells in the right ventricular myocardium after intracoronary injection in a large animal model of pulmonary hypertension

摘要

Abstract Background aims In this study, we demonstrate long-term persistence of human mesenchymal stromal cells (hMSCs) after intracoronary injection in a large animal model of pulmonary hypertension (PH). Methods Commercially available placenta-derived hMSCs were used. Experiments were conducted on 14 female Yorkshire swine. Four animals served as controls, and 10 underwent pulmonary vein (PV) banding. After 12?±?2 weeks, PH and PV dysfunction were confirmed by right heart catheterization and cardiac magnetic resonance imaging. hMSCs were injected in the marginal branch of the right coronary artery. Tissues were harvested 6, 9 or 24 days after infusion. Results After 12?±?2 weeks after PV banding, all subjects had increased mean pulmonary artery pressure (13.6?±?3.6 versus 30.8?±?4.5?mm Hg, P??0.007) and a decrease in right ventricular ejection fraction from 51.7?±?5.7% versus 30.5?±?11.3% (P?=?0.003). Intracoronary injection of hMSCs was well tolerated. Up to 24 days after hMSC injection, immunohistochemistry revealed extravascular viable human CD105+