Cardiac repair using regenerating neonatal heart tissue-derived extracellular vesicles

IF 14.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Nature Communications Pub Date : 2025-02-03 DOI:10.1038/s41467-025-56384-x

Hanjing Li, Yining Liu, Yuqing Lin, Sijia Li, Chenlu Liu, Ao Cai, Wei Li, Wanyu Zhang, Xinlu Gao, Zhongyu Ren, Haoyu Ji, Yang Yu, Xiuxiu Wang, Wenya Ma, Ning Wang, Dan Zhao, Tianlong Li, Yu Liu, Benzhi Cai

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Abstract

Neonatal mammalian hearts are capable of regenerating by inducing cardiomyocyte proliferation after injury. However, this regenerative capability in adult mammalian hearts almost disappears. Extracellular vesicles (EVs) have been shown to play vital cardioprotective roles in heart repair. Here, we report that EVs from regenerating neonatal heart tissues, after apical resection surgery (AR-Neo-EVs), exhibit stronger pro-proliferative, anti-apoptotic, and pro-angiogenesis activities than EVs from neonatal mouse cardiac tissues (Neo-EVs), effects which are absent in adult mouse heart-derived EVs (Adu-EVs). Proteomic analysis reveals the expression of Wdr75 protein, a regulator of p53, is higher in AR-Neo-EVs than in Neo-EVs. It is shown the regenerative potential of AR-Neo-EVs is abrogated when Wdr75 is knocked down. We further show that delivery of AR-Neo-EVs by sodium alginate hydrogel microspheres is an effective treatment in myocardial infraction. This work shows the potential of using EVs from regenerating tissue to trigger protective and regenerative mechanisms.

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利用再生新生儿心脏组织来源的细胞外囊泡进行心脏修复

哺乳动物新生心脏损伤后可通过诱导心肌细胞增殖再生。然而，成年哺乳动物心脏的这种再生能力几乎消失了。细胞外囊泡（EVs）已被证明在心脏修复中发挥重要的心脏保护作用。在这里，我们报道了来自根尖切除手术后再生新生儿心脏组织的EVs （AR-Neo-EVs）比来自新生小鼠心脏组织的EVs （Neo-EVs）表现出更强的促增殖、抗凋亡和促血管生成活性，而这些作用在成年小鼠心脏来源的EVs （Adu-EVs）中没有。蛋白质组学分析显示，p53的调节因子Wdr75蛋白在ar - neo - ev中的表达高于neo - ev。结果表明，当Wdr75被敲除时，ar - neo - ev的再生潜力被取消。我们进一步表明，通过海藻酸钠水凝胶微球递送ar - neo - ev是一种有效的心肌梗死治疗方法。这项工作显示了利用再生组织中的电动汽车触发保护和再生机制的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature Communications Biological Science Disciplines-

CiteScore

24.90

自引率

2.40%

发文量

6928

审稿时长

3.7 months

期刊介绍： Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.

文献相关原料

公司名称

产品信息

索莱宝

DAPI

麦克林

sodium alginate solution

阿拉丁

mineral oil