Lee Hyeryon, Lee Jae Chul, Kwon Jung Hyun, Kim Kwan Chang, Cho Min-Sun, Yang Yoon Sun, Oh Wonil, Choi Soo Jin, Seo Eun-Seok, Lee Sang-Joon, Wang Tae Jun, Hong Young Mi
Department of Pediatrics, Ewha Womans University School of Medicine, Seoul, Korea.
Department of Thoracic and Cardiovascular Surgery, Ewha Womans University School of Medicine, Seoul, Korea.
J Korean Med Sci. 2015 May;30(5):576-85. doi: 10.3346/jkms.2015.30.5.576. Epub 2015 Apr 15.
Pulmonary arterial hypertension (PAH) causes right ventricular failure due to a gradual increase in pulmonary vascular resistance. The purposes of this study were to confirm the engraftment of human umbilical cord blood-mesenchymal stem cells (hUCB-MSCs) placed in the correct place in the lung and research on changes of hemodynamics, pulmonary pathology, immunomodulation and several gene expressions in monocrotaline (MCT)-induced PAH rat models after hUCB-MSCs transfusion. The rats were grouped as follows: the control (C) group; the M group (MCT 60 mg/kg); the U group (hUCB-MSCs transfusion). They received transfusions via the external jugular vein a week after MCT injection. The mean right ventricular pressure (RVP) was significantly reduced in the U group after the 2 week. The indicators of RV hypertrophy were significantly reduced in the U group at week 4. Reduced medial wall thickness in the pulmonary arteriole was noted in the U group at week 4. Reduced number of intra-acinar muscular pulmonary arteries was observed in the U group after 2 week. Protein expressions such as endothelin (ET)-1, endothelin receptor A (ERA), endothelial nitric oxide synthase (eNOS) and matrix metalloproteinase (MMP)-2 significantly decreased at week 4. The decreased levels of ERA, eNOS and MMP-2 immunoreactivity were noted by immnohistochemical staining. After hUCB-MSCs were administered, there were the improvement of RVH and mean RVP. Reductions in several protein expressions and immunomodulation were also detected. It is suggested that hUCB-MSCs may be a promising therapeutic option for PAH.
肺动脉高压(PAH)由于肺血管阻力逐渐增加而导致右心室衰竭。本研究的目的是确认置于肺内正确位置的人脐带血间充质干细胞(hUCB-MSCs)的植入情况,并研究在hUCB-MSCs输注后,在野百合碱(MCT)诱导的PAH大鼠模型中血流动力学、肺病理学、免疫调节和几种基因表达的变化。大鼠分组如下:对照组(C组);M组(MCT 60 mg/kg);U组(hUCB-MSCs输注)。在注射MCT一周后,它们通过颈外静脉接受输注。2周后,U组的平均右心室压力(RVP)显著降低。第4周时,U组右心室肥厚指标显著降低。第4周时,U组肺小动脉中膜厚度减小。2周后,U组腺泡内肌性肺动脉数量减少。第4周时,内皮素(ET)-1、内皮素受体A(ERA)、内皮型一氧化氮合酶(eNOS)和基质金属蛋白酶(MMP)-2等蛋白表达显著下降。免疫组织化学染色显示ERA、eNOS和MMP-2免疫反应性水平降低。给予hUCB-MSCs后,右心室肥厚和平均RVP得到改善。还检测到几种蛋白表达降低和免疫调节作用。提示hUCB-MSCs可能是PAH一种有前景的治疗选择。