Abstract 12041: Therapeutic Effects of Induced Pluripotent Stem Cells Secretome In Monocrotaline-induced Pulmonary Arterial Hypertension Rats

Introduction: Pulmonary arterial hypertension (PAH) is a progressive disorder characterized by the increased vascular resistance and the remodeling of pulmonary arteries. Evidences of accumulated inflammatory cells in the lung suggested that chronic inflammation might play a role in PAH. Regenerative cell therapy emerged as a potential treatment for PAH through regulating the host’s immune response. Hypothesis: The secretome of induced pluripotent stem cells (iPSCs) was investigated for their preventive and therapeutic effects in the pathogenesis of monocrotaline (MCT)-induced PAH rat. Methods: PAH was developed by the subcutaneous injection of MCT in rats. The conditioned medium of cultured iPSCs (iPSC CM) was applied daily in prevention (an hour after MCT injection) or reversal (14 days after MCT injection) by IP injection throughout the full 28 days of experiment. The effects of iPSC CM were interpreted by the analyses of systolic pressure (RVSP) and the hypertrophy index of right ventricle, also the regulation of inflammation in lung and the underlying mechanism. Results: Both prevention and reversal, the hemodynamic values of RVSP and hypertrophy index were significantly improved in MCT-induced PAH rats after iPSC CM treatment. Attenuated expression of pro-inflammatory M1 macrophage markers was observed in either the lung of MCT-induced PAH rats or in co-cultured human M1 macrophages after iPSC CM treatment. To investigate the potential molecules secreted by iPSCs into iPSC CM, two major ingredients, named α1-antitrypsin and feutin-a, were identified by protein mass spectrometry and confirmed by western blotting with specific antibodies. Both components were mentioned to be involved in the anti-inflammatory effects observed in various lung diseases. Conclusions: In this study, iPSC CM represented therapeutic benefits on MCT-induced PAH rats though attenuating inflammation. Molecules exhibit anti-inflammatory potential existed in the iPSC CM, such as α1-antitrypsin and feutin-a, might hold the promise as new therapeutics of regenerative cell therapy via paracrine mechanism.