Adipose-derived stem cells attenuate pulmonary arterial hypertension and ameliorate pulmonary arterial remodeling in monocrotaline-induced pulmonary hypertensive rats
Adipose-derived stem cells attenuate pulmonary arterial hypertension and ameliorate pulmonary arterial remodeling in monocrotaline-induced pulmonary hypertensive rats
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DOI：
10.3109/10641963.2014.954710
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发表时间：
2015-01-01
影响因子：
12.3
通讯作者：
Xie, Liangdi
中科院分区：
文献类型：
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作者：
Luo, Li;Lin, Taijie;Xie, Liangdi
我们研究了脂肪源性干细胞（ADSC）移植对野百合碱（MCT）诱导的肺动脉高压大鼠结构重建和肺动脉压的影响。实验一：32只雄性SD大鼠随机分为4组（n = 8/组）：3个ADSC处理组和正常对照组（Ctrl）。分别以10（5）、10（6）和10（7）个细胞通过左颈静脉施用ADSC，并且显示10（6）个细胞/ml的细胞密度是最佳的。GFP标记的ADSC在肺中被鉴定并分化为内皮样细胞。实验二将96只雄性SD大鼠随机分为对照组、MCT诱导的肺动脉高压（PAH）组和脂肪干细胞治疗PAH组（ADSCs），每组32只。MCT给药后两周，ADSC组通过颈外静脉接受1 x 10（6）个ADSC。与PAH大鼠相比，ADSC治疗后1、2和3周大鼠的平均肺动脉压降低（18.63 +/- 2.15 mmHg对比24.53 +/- 2.90 mmHg; 23.07 +/-2.84 mmHg对比33.18 +/- 2.30 mmHg; 22.98 +/- 2.34 mmHg对比36.38 +/- 3.28 mmHg，p < 0.05）。同时，右心肥大指数（36.2 1 ± 4.27%对41.01 ± 1.29%; 39.47 ± 4.02%对48.75 ± 2.13%; 41.02 +/- 0.9%对50.52 +/-1.49%，p < 0.05），在ADSC治疗后的这些时间点，PAH大鼠的壁/腔厚度比以及壁/腔面积显著降低，与未治疗的PAH大鼠相比。总之，脂肪干细胞可以定植于肺动脉，减轻肺动脉高压，改善肺动脉重构。
We investigated the effect of adipose-derived stem cells (ADSCs) transplantation effects on structural remodeling and pulmonary artery pressure in monocrotaline (MCT)-induced pulmonary hypertensive rats. In the first experiment, 32 male Sprague-Dawley (SD) rats were randomly divided into four groups (n = 8/group): 3 ADSCs treated groups and normal control (Ctrl). ADSCs were administered through the left jugular vein at 10(5), 10(6) and 10(7) cells, respectively, and a cell density of 10(6) cells/ml was shown to be optimal. The GFP-tagged ADSCs were identified in the lungs and differentiated into endothelial-like cells. In the second experiment, 96 male SD rats were randomly divided into three groups (n = 32/group): Ctrl, MCT-induced pulmonary arterial hypertension (PAH), and PAH treated with ADSCs (ADSCs). Two weeks post-MCT administration, the ADSCs group received 1 x 10(6) ADSCs via the external jugular vein. Compared to PAH rats, mean pulmonary arterial pressure was decreased in rats at 1, 2, and 3 weeks after ADSCs-treatment (18.63 +/- 2.15 mmHg versus 24.53 +/- 2.90 mmHg; 23.07 +/- 2.84mmHg versus 33.18 +/- 2.30 mmHg; 22.98 +/- 2.34 mmHg versus 36.38 +/- 3.28 mmHg, p < 0.05). Meanwhile, the right heart hypertrophy index (36.2 1 +/- 4.27% versus 41.01 +/- 1.29%; 39.47 +/- 4.02% versus 48.75 +/- 2.13%; 41.02 +/- 0.9% versus 50.52 +/- 1.49%, p < 0.05, respectively), ratio of wall/lumen thickness, as well as the wall/lumen area were significantly reduced in PAH rats at these time points following ADSCs-treatment, as compared with untreated PAH rats. In summary, ADSCs may colonize the pulmonary arteries, attenuate pulmonary arterial hypertension and ameliorate pulmonary arterial remodeling.