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

2017-06-01 13:16:50

Cytotherapy  June 1 2017


Roza Badr Eslam, Kevin Croce, Fernanda Marinho Mangione, Robert Musmann, Jane A. Leopold, Richard N. Mitchell, Aaron B. Waxman


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). 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. After 12±2 weeks after PV banding, all subjects had increased mean pulmonary artery pressure (13.6±3.6 versus 30.8±4.5mm 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+ mononuclear cells in the right ventricle (RV) that were Ki67+. This was confirmed by fluorescence in situ hybridization. CD45+ porcine inflammatory cells were identified, commonly seen adjacent to areas of healing microscopic infarction that likely dated to the time of the original hMSC injection. Anti-CD31 staining produced strong signals in areas of injected hMSCs. Immunohistochemistry staining for vascular cell adhesion molecule-1 showed upregulation in the clusters, where mononuclear cells were located.

Empire Genomic's Custom RP-11 Probes were used in this publication.

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