Abstract 58: Intratracheal Delivery of Autologous Bone Marrow-derived Cells Attenuate Muscularization and Inflammation in Lungs of Monocrotaline-induced Pulmonary Hypertension Model Rats.

Abstract

Background: Vascular remodeling and inflammation contribute to the pathogenesis and/or development of pulmonary hypertension. Bone marrow-derived cells (BMCs) include mesenchymal stem cells and progenitor cells play critical role in tissue repair as well as anti-inflammatory effects. Aim of this study was to investigate the effect of intratracheal delivered BMCs on monocrotaline (MCT)-induced muscuralization and inflammation in rat lung. METHODS: BMCs were isolated and cultured for 3 weeks. Seven days following MCT (60 mg/kg) treatment, DiI labeled autologous BMCs were intratracheally delivered to male Sprague-Dawley rats. Twenty-eight days following the MCT treatment, rats had hemodynamic studies. Hearts and lungs were removed to evaluate right ventricular (RV) hypertrophy and lung pathologies. Results: MCT treated rats had increased RV systolic pressure (RVSP), RV weight as well as wall thickness of small pulmonary arteries and alveolar septum thickness than those of placebo-treated control rats (all p values <0.01). Intratracheal delivery of autologous BMCs (1x106) 7 days after MCT prevented the increase in RVSP at 4 weeks compared with MCT alone (45.1 ± 2.23 versus 35.0 ± 3.84 mmHg, respectively; p<0.05). Furthermore, the intratracheal delivery of BMCs significantly attenuated the pulmonary vessel wall thickness (54.4 % ± 2.25 versus 17.8 % ± 2.69, p<0.01), and alveolar septum thickening (155.1 % ± 1.56 versus 114.2 % ± 1.16, p<0.01) accompanied with decreased numbers of inflammatory cells in perivascular areas and expression of proinflammatory cytokines compared with MCT alone. Immunohistochemical studies showed monocyte-like shaped DiI positive cells distributed in alveolar areas in BMCs delivered lungs, and some of those DiI positive cells expressed CD 68 and alpha smooth muscle cell actin. Conclusion: Intratracheal delivery of autologous BMCs prevented MCT-induced pulmonary hypertension by attenuation of vascular muscularization and inflammation in rat lung.