Institute for Laboratory Animal Research, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, Sichuan, China.
Department of Gastroenterology, People's Hospital of Tibet Autonomous Region, Lhasa, 850000, Tibet, China.
Hum Cell. 2024 Jan;37(1):214-228. doi: 10.1007/s13577-023-01009-y. Epub 2023 Nov 15.
Pulmonary arterial hypertension (PAH) is a chronic disease thatultimately progresses to right-sided heart failure and death. Erythropoietin (EPO) has been shown to have therapeutic potential in cardiovascular diseases, including PAH. In this study, we aimed to investigate the improvement effect of EPO pretreated bone marrow mesenchymal stem cells (BMSCs) on PAH. BMSCs were obtained from the bone marrow of male SD rats. Female rats were randomly divided into six groups, including control group, monocrotaline (MCT)-induced group, and four groups with different doses of EPO pretreated BMSCs. Lung tissue was taken for testing at 2 weeks of treatment. Our results showed EPO promoted homing and endothelial cell differentiation of BMSCs in the lung tissues of PAH rats. EPO and BMSCs treatment attenuated pulmonary arterial pressure, polycythemia, and pulmonary artery structural remodeling. Furthermore, BMSCs inhibited pulmonary vascular endothelial-to-mesenchymal transition (EndoMT) in PAH rats, which was further suppressed by EPO in a concentration-dependent manner. Meanwhile, EPO and BMSC treatment elevated pulmonary angiogenesis in PAH rats. BMSCs inhibited TNF-α, IL-1β, IL-6, and MCP-1 in lung tissues of PAH rats, which was further decreased by EPO in a concentration-dependent manner. Thus, EPO improved pulmonary hypertension (PH) by promoting the homing and differentiation of BMSCs in lung tissue.
肺动脉高压（PAH）是一种慢性疾病，最终会发展为右心衰竭和死亡。促红细胞生成素（EPO）已被证明在心血管疾病中具有治疗潜力，包括 PAH。在这项研究中，我们旨在研究 EPO 预处理骨髓间充质干细胞（BMSCs）对 PAH 的改善作用。BMSCs 从雄性 SD 大鼠的骨髓中获得。雌性大鼠随机分为六组，包括对照组、单环酸（MCT）诱导组和四组不同剂量的 EPO 预处理 BMSCs 组。在治疗 2 周时取肺组织进行检测。我们的结果表明，EPO 促进了 PAH 大鼠肺组织中 BMSCs 的归巢和内皮细胞分化。EPO 和 BMSCs 治疗可减轻肺动脉压、红细胞增多症和肺动脉结构重塑。此外，BMSCs 抑制了 PAH 大鼠的肺血管内皮到间充质转化（EndoMT），EPO 以浓度依赖性方式进一步抑制了这种转化。同时，EPO 和 BMSC 治疗可促进 PAH 大鼠的肺血管生成。BMSCs 抑制了 PAH 大鼠肺组织中的 TNF-α、IL-1β、IL-6 和 MCP-1，EPO 以浓度依赖性方式进一步降低了这些因子的水平。因此，EPO 通过促进 BMSCs 在肺组织中的归巢和分化来改善肺动脉高压（PH）。
