脂肪来源干细胞来源的外泌体递送 SAV-siRNA 治疗心肌梗死。
Delivery of SAV-siRNA via Exosomes from Adipose-Derived Stem Cells for the Treatment of Myocardial Infarction.
机构信息
Department of Cardiac Surgery, The Fifth Affiliated Hospital of Sun Yat-Sen University, No. 52, Meihua East Road, Zhuhai, Guangdong, People's Republic of China.
Center for Infection and Immunity, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, No. 52, Meihua East Road, Zhuhai, Guangdong, People's Republic of China.
出版信息
Tissue Eng Regen Med. 2023 Dec;20(7):1063-1077. doi: 10.1007/s13770-023-00588-z. Epub 2023 Oct 6.
BACKGROUND
Myocardial infarction (MI) leads to cardiomyocyte death, poor cardiac remodeling, and heart failure, making it a major cause of mortality and morbidity. To restore cardiac pumping function, induction of cardiomyocyte regeneration has become a focus of academic interest. The Hippo pathway is known to regulate cardiomyocyte proliferation and heart size, and its inactivation allows adult cardiomyocytes to re-enter the cell cycle.
METHODS
In this study, we investigated whether exosomes from adipose-derived stem cells (ADSCs) could effectively transfer siRNA for the Hippo pathway regulator Salvador (SAV) into cardiomyocytes to induce cardiomyocyte regeneration in a mouse model of MI.
RESULTS
Our results showed that exosomes loaded with SAV-siRNA effectively transferred siRNA into cardiomyocytes and induced cardiomyocyte re-entry into the cell cycle, while retaining the previously demonstrated therapeutic efficacy of ADSC-derived exosomes to improve post-infarction cardiac function through anti-fibrotic, pro-angiogenic, and other effects.
CONCLUSIONS
Our findings suggest that siRNA delivery via ADSC-derived exosomes may be a promising approach for the treatment of MI.
背景
心肌梗死（MI）导致心肌细胞死亡、心脏重构不良和心力衰竭，是导致死亡率和发病率的主要原因。为了恢复心脏的泵血功能，诱导心肌细胞再生已成为学术研究的重点。已知 Hippo 通路调节心肌细胞增殖和心脏大小，其失活可使成年心肌细胞重新进入细胞周期。
方法
在这项研究中，我们研究了脂肪来源干细胞（ADSCs）来源的外泌体是否可以将 Hippo 通路调节剂 Salvador（SAV）的 siRNA 有效递送至心肌细胞，以诱导 MI 小鼠模型中的心肌细胞再生。
结果
我们的结果表明，负载 SAV-siRNA 的外泌体可有效将 siRNA 递送至心肌细胞，并诱导心肌细胞重新进入细胞周期，同时保留 ADSC 衍生的外泌体先前证明的通过抗纤维化、促血管生成等作用改善梗死后心功能的治疗功效。
结论
我们的研究结果表明，通过 ADSC 衍生的外泌体递送 siRNA 可能是治疗 MI 的一种有前途的方法。
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