Effect of dose, dosing intervals, and hypoxic stress on the reversal of pulmonary hypertension by mesenchymal stem cell extracellular vesicles.
Effect of dose, dosing intervals, and hypoxic stress on the reversal of pulmonary hypertension by mesenchymal stem cell extracellular vesicles.
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DOI：
10.1177/20458940211046137
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发表时间：
2021-10
影响因子：
2.6
通讯作者：
Liang OD
中科院分区：
文献类型：
--
作者：
Klinger JR;Pereira M;Tatto MD;Dooner MS;Wen S;Quesenberry PJ;Liang OD
间充质干细胞细胞外囊泡（MSC EV）逆转肺动脉高压，但关于什么剂量是有效的以及需要多久给予的信息很少。本研究检查了剂量减少和使用较长给药间隔的影响以及EV收集前MSC缺氧应激的影响。成年雄性大鼠缺氧三周后，用苏根5416诱发肺动脉高压使用以下方案之一，在从缺氧中移除的当天，用MSC EV或磷酸盐缓冲盐水注射（SuHx-肺动脉高压）：（1）每日一次，持续三天，剂量为0.2、1、5、20和100 µg/kg，（2）每周一次（100 μg/kg）持续5周，（3）每隔一周一次（100 μg/kg）持续10周，（4）每天一次（20 μg/kg）持续3天，使用从暴露于低氧48小时的MSC（HxEV）或保持在常氧条件下的MSC（NxEV）获得的EV。当以20或100 μg/kg剂量给药时，MSC EV逆转了右心室收缩压（RVSP）、右心室至左心室+间隔重量（RV/LV+S）和≤50 µm肺血管肌化指数的增加。与常氧对照组相比，每周一次磷酸盐缓冲盐水治疗5周或每隔一周治疗10周的SuHx-肺动脉高压大鼠的RVSP、RV/LV+S和肌化指数显著升高，但给予MSC EV的SuHx-肺动脉高压大鼠的RVSP、RV/LV+S和肌化指数没有显著升高。NxEV和HxEV均显著降低RVSP、RV/LV+S和肌化指数，但治疗组间无差异。MSC EV在以比先前报道的更低剂量和更长的给药间隔给予时有效逆转SuHx-肺动脉高压。低血压应激并不能增强MSC EV逆转肺动脉高压的疗效。这些发现支持MSC EV作为肺动脉高压长期治疗的可行性。
Mesenchymal stem cell extracellular vesicles (MSC EVs) reverse pulmonary hypertension, but little information is available regarding what dose is effective and how often it needs to be given. This study examined the effects of dose reduction and use of longer dosing intervals and the effect of hypoxic stress of MSC prior to EV collection. Adult male rats with pulmonary hypertension induced by Sugen 5416 and three weeks of hypoxia (SuHx-pulmonary hypertension) were injected with MSC EV or phosphate buffered saline the day of removal from hypoxia using one of the following protocols: (1) Once daily for three days at doses of 0.2, 1, 5, 20, and 100 µg/kg, (2) Once weekly (100 µg/kg) for five weeks, (3) Once every other week (100 µg/kg) for 10 weeks, (4) Once daily (20 µg/kg) for three days using EV obtained from MSC exposed to 48 h of hypoxia (HxEV) or MSC kept in normoxic conditions (NxEV). MSC EV reversed increases in right ventricular systolic pressure (RVSP), right ventricular to left ventricle + septum weight (RV/LV+S), and muscularization index of pulmonary vessels ≤50 µm when given at doses of 20 or 100 μg/kg. RVSP, RV/LV+S, and muscularization index were significantly higher in SuHx-pulmonary hypertension rats treated once weekly with phosphate buffered saline for five weeks or every other week for 10 weeks than in normoxic controls, but not significantly increased in SuHx-pulmonary hypertension rats given MSC EV. Both NxEV and HxEV significantly reduced RVSP, RV/LV+S, and muscularization index, but no differences were seen between treatment groups. MSC EV are effective at reversing SuHx-pulmonary hypertension when given at lower doses and longer dosing intervals than previously reported. Hypoxic stress does not enhance the efficacy of MSC EV at reversing pulmonary hypertension. These findings support the feasibility of MSC EV as a long-term treatment for pulmonary hypertension.
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影响因子：
3.3
作者：
da Silva, Claudia Lobato;Goncalves, Raquel;Cabral, Joaquim M. S.
通讯作者：
Cabral, Joaquim M. S.
影响因子：
6
作者：
Lo Sicco C;Reverberi D;Balbi C;Ulivi V;Principi E;Pascucci L;Becherini P;Bosco MC;Varesio L;Franzin C;Pozzobon M;Cancedda R;Tasso R
通讯作者：
Tasso R
DOI：
10.33594/000000102
发表时间：
2019-01-01
期刊：
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
影响因子：
--
作者：
Collino, Federica;Lopes, Jarlene Alecia;Lindoso, Rafael Soares
通讯作者：
Lindoso, Rafael Soares
DOI：
10.1164/rccm.201701-0170oc
发表时间：
2017-11-15
影响因子：
24.7
作者：
Morrison, Thomas J.;Jackson, Megan V.;Krasnodembskaya, Anna D.
通讯作者：
Krasnodembskaya, Anna D.
DOI：
10.1165/rcmb.2019-0154oc
发表时间：
2020-05-01
影响因子：
6.4
作者：
Klinger, James R.;Pereira, Mandy;Liang, Olin D.
通讯作者：
Liang, Olin D.