Umar Soban, de Visser Yvonne P, Steendijk Paul, Schutte Cindy I, Laghmani El Houari, Wagenaar Gerry T M, Bax Wilhelmina H, Mantikou Eleni, Pijnappels Daniel A, Atsma Douwe E, Schalij Martin J, van der Wall Ernst E, van der Laarse Arnoud
Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
Am J Physiol Heart Circ Physiol. 2009 Nov;297(5):H1606-16. doi: 10.1152/ajpheart.00590.2009. Epub 2009 Sep 25.
Pulmonary arterial hypertension (PAH) is a chronic lung disease that leads to right ventricular (RV) hypertrophy (RVH), remodeling, and failure. We tested treatment with bone marrow-derived mesenchymal stem cells (MSCs) obtained from donor rats with monocrotaline (MCT)-induced PAH to recipient rats with MCT-induced PAH on pulmonary artery pressure, lung pathology, and RV function. This model was chosen to mimic autologous MSC therapy. On day 1, PAH was induced by MCT (60 mg/kg) in 20 female Wistar rats. On day 14, rats were treated with 10(6) MSCs intravenously (MCT + MSC) or with saline (MCT60). MSCs were obtained from donor rats with PAH at 28 days after MCT. A control group received saline on days 1 and 14. On day 28, the RV function of recipient rats was assessed, followed by isolation of the lungs and heart. RVH was quantified by the weight ratio of the RV/(left ventricle + interventricular septum). MCT induced an increase of RV peak pressure (from 27 + or - 5 to 42 +/- 17 mmHg) and RVH (from 0.25 + or - 0.04 to 0.47 + or - 0.12), depressed the RV ejection fraction (from 56 + or - 11 to 43 + or - 6%), and increased lung weight (from 0.96 + or - 0.15 to 1.66 + or - 0.32 g), including thickening of the arteriolar walls and alveolar septa. MSC treatment attenuated PAH (31 + or - 4 mmHg) and RVH (0.32 + or - 0.07), normalized the RV ejection fraction (52 + or - 5%), reduced lung weight (1.16 + or - 0.24 g), and inhibited the thickening of the arterioles and alveolar septa. We conclude that the application of MSCs from donor rats with PAH reduces RV pressure overload, RV dysfunction, and lung pathology in recipient rats with PAH. These results suggest that autologous MSC therapy may alleviate cardiac and pulmonary symptoms in PAH patients.
肺动脉高压（PAH）是一种慢性肺部疾病，可导致右心室（RV）肥厚（RVH）、重塑和衰竭。我们用从用野百合碱（MCT）诱导的PAH供体大鼠获得的骨髓间充质干细胞（MSCs）对用MCT诱导的PAH受体大鼠进行治疗，观察其对肺动脉压力、肺部病理和RV功能的影响。选择该模型来模拟自体MSC治疗。第1天，用MCT（60mg/kg）诱导20只雌性Wistar大鼠发生PAH。第14天，大鼠静脉注射10(6)个MSCs（MCT+MSC组）或生理盐水（MCT60组）。MSCs于MCT处理28天后从患有PAH的供体大鼠中获取。对照组在第1天和第14天接受生理盐水注射。第28天，评估受体大鼠的RV功能，随后分离肺和心脏。通过RV/（左心室+室间隔）的重量比来量化RVH。MCT使RV峰值压力升高（从27±5mmHg升至42±17mmHg）以及RVH增加（从0.25±0.04升至0.47±0.12），降低RV射血分数（从56±11%降至43±6%），并增加肺重量（从0.96±0.15g增至1.66±0.32g），包括小动脉壁和肺泡间隔增厚。MSC治疗减轻了PAH（31±4mmHg）和RVH（0.32±0.07），使RV射血分数恢复正常（52±5%），减轻了肺重量（1.16±0.24g），并抑制了小动脉和肺泡间隔增厚。我们得出结论，应用来自患有PAH的供体大鼠的MSCs可降低患有PAH的受体大鼠的RV压力过载、RV功能障碍和肺部病理改变。这些结果表明自体MSC治疗可能减轻PAH患者的心脏和肺部症状。
