Studying the Effect of Cell Therapy by Endothelial Progenitor Cells With and Without Heme-oxygenase Inducers in Induced Pulmonary Hypertension Rat Model

Purpose: We investigated whether or not intravenous injection of bone marrow-derived endothelial progenitor cells (EPCs), alone or combined with Heme-oxygenase (HO) inducer can restore pulmonary hemodynamics and increase microvascular perfusion in the rat monocrotaline (MCT) model of pulmonary artery hypertension (PAH) so improve right ventricle performance. Material and Methods: Rats were divided into control, rats with PAH, PAH rats receiving EPCs, PAH rats receiving HO-1 inducer (cobalt protoporphyrin) and PAH rats receiving EPCs plus HO-1 inducer. After 1 month, right ventricular function, was assessed. Gene expression of pro ANP, SDF-1, Bax/Bcl-2, MMP-9 were studied. Results: Heart functions showed improvement in all the treated groups compared to PAH group. Gene expression demonstrated that proANP, MMP-9 and Bax were downregulated while Bcl-2 and SDF-1 were upregulated. Conclusion: The present study proved that, administration of BM-EPCs alone, HO-1 alone or EPCs plus HO-1 produce therapeutic effect in restoring pulmonary hemodynamics and so improving right ventricle performance in PAH. This effect may be through antiapoptotic action of EPCs and HO-1.