MiR-101a loaded extracellular nanovesicles as bioactive carriers for cardiac repair.

MiR-101a loaded extracellular nanovesicles as bioactive carriers for cardiac repair.
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DOI:
10.1016/j.nano.2020.102201
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发表时间:
2020-07
期刊:
Nanomedicine : nanotechnology, biology, and medicine
影响因子:
--
通讯作者:
Nguyen J
Nguyen J
中科院分区:
其他
文献类型:
--
作者:
Wang J;Lee CJ;Deci MB;Jasiewicz N;Verma A;Canty JM;Nguyen J

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心肌梗死(MI)仍然是世界范围内死亡的主要原因。尽管心肌梗死的治疗取得了重大进展,但许多在急性事件中幸存下来的人仍面临着慢性心脏病发病率的高风险。在这里,我们开发了一种无细胞治疗方法,利用微量(MI)RNA-101a的抗纤维化作用,并利用间充质干细胞(MSC)细胞外纳米囊(Env)的多方面再生活性。虽然大多数MSC env需要通过心肌内注射来发挥治疗效果,但我们已经开发出可以以微创方式给药的MSC env,所有这些都保持了治疗活性。与对照组相比,负载miR-101a后,MSC Envs显著缩小了梗塞面积(12±2.4%比21.4±5.7%),增加了射血分数(53.6±7.6%比40.3±6.0%)和短轴缩短率(23.6±4.3%比16.6±3.0%)。这些发现意义重大,因为它们代表了微创心脏疗法发展的进步。
Myocardial infarction (MI) remains a major cause of mortality worldwide. Despite significant advances in MI treatment, many who survive the acute event are at high risk of chronic cardiac morbidity. Here we developed a cell-free therapeutic that capitalizes on the antifibrotic effects of micro(mi)RNA-101a and exploits the multi-faceted regenerative activity of mesenchymal stem cell (MSC) extracellular nanovesicles (eNVs). While the majority of MSC eNVs require local delivery via intramyocardial injection to exert therapeutic efficacy, we have developed MSC eNVs that can be administered in a minimally invasive manner, all while remaining therapeutically active. When loaded with miR-101a, MSC eNVs substantially decreased infarct size (12 ± 2.4% vs. 21.4 ± 5.7%) and increased ejection fraction (53.6 ± 7.6% vs. 40.3 ± 6.0%) and fractional shortening (23.6 ± 4.3% vs. 16.6 ± 3.0%) compared to control. These findings are significant as they represent an advance in the development of minimally invasive cardio-therapies.
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