Central Research Laboratory, the Second Hospital of Shandong University, Jinan, China.
Am J Med Sci. 2012 May;343(5):402-6. doi: 10.1097/MAJ.0b013e31822dc5d3.
Pulmonary hypertension (PH) is a rapidly progressive and fatal disease. In recent years, despite drug treatment made significant progress, the prognosis of patients with advanced PH remains extremely poor. The authors implanted bone marrow-derived mesenchymal stem cells (BMSCs) intravenously into the PH model rats and observed the effect of MSCs on right ventricular (RV) impairments.
BMSCs were isolated, cultured from bone marrow of rats and stained with the cross-linkable membrane dye in vitro. One week after, a PH model was induced by subcutaneous injection of monocrotaline, the animals were randomly divided into 4 groups (n = 20 in each group): I, control; II, MSCs implantation; III, PH and IV, PH + MSCs implantation. Two weeks after MSCs implantation, the authors observed the MSC survival and transformation by immunofluorescence microscopy. On the other hand, RV hypertrophy and the elevation of systolic pressure were detected by echocardiography.
Three weeks after monocrotaline injection, RV systolic pressure, mean right ventricular pressure and mean pulmonary arterial pressure were significantly elevated in group III than in group I and II (P < 0.05) but significantly lower in group IV than in group III (P < 0.05). These results showed that implantation of MSCs could improve RV impairments caused by experimental PH. Histochemical results confirmed that transplanted MSCs were still alive after 2 weeks and part of the cells could differentiate into pulmonary vascular endothelial cells.
Intravenous implantation of MSCs could significantly reduce or even reverse the progression of MCT-induced PH, improve cardiac function and hemodynamics.
肺动脉高压(PH)是一种快速进展且致命的疾病。近年来,尽管药物治疗取得了显著进展,但晚期 PH 患者的预后仍然极差。作者将骨髓间充质干细胞(BMSCs)静脉内植入 PH 模型大鼠,并观察 MSCs 对右心室(RV)损伤的影响。
BMSCs 从大鼠骨髓中分离、培养,并在体外用交联膜染料染色。1 周后,皮下注射野百合碱诱导 PH 模型,将动物随机分为 4 组(每组 n = 20):I 组,对照组;II 组,MSCs 植入组;III 组,PH 组;IV 组,PH+MSCs 植入组。MSCs 植入 2 周后,作者通过免疫荧光显微镜观察 MSC 的存活和转化。另一方面,通过超声心动图检测 RV 肥大和收缩压升高。
野百合碱注射 3 周后,III 组 RV 收缩压、平均右心室压和平均肺动脉压明显高于 I 组和 II 组(P < 0.05),但明显低于 IV 组(P < 0.05)。这些结果表明,植入 MSCs 可改善实验性 PH 引起的 RV 损伤。组织化学结果证实,移植的 MSCs 在 2 周后仍存活,部分细胞可分化为肺血管内皮细胞。
静脉内植入 MSCs 可显著减轻甚至逆转 MCT 诱导的 PH 进展,改善心功能和血液动力学。