Effect of dose, dosing intervals, and hypoxic stress on the reversal of pulmonary hypertension by mesenchymal stem cell extracellular vesicles

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Posted: 2022-01-06 20:00:00
Rationale: 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. Methods: 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). Main results: 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. Conclusions: 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. Keywords: exosomes; pulmonary vascular remodeling; right ventricular hypertrophy.

参考サイト PubMed: exsome


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バイオクイックニュース日本語版:エクソソーム特集

バイオクイックニュース日本語版
2月 06, 2019 bioassociates2

Nischarin発現細胞からのエキソソームは乳癌細胞の運動性と腫瘍増殖を減少させることが発見された。薬剤とNischarin発現エクソソームの併用で、優れた乳癌治療の可能性。

米国ルイジアナ州立大学公衆衛生学(LSU Health)のSuresh K Alahari博士は、乳癌細胞の遊走や動きの制御など、さまざまな生物学的プロセスに関与する新規タンパク質、Nischarinを発見した。 彼の研究室は、Nischarinが腫瘍抑制因子として機能することを示した。この研究はより良い癌治療につながるかもしれない。 現在の研究で研究チームは エクソソーム 放出におけるNischarinの機能を調べた。…

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