Cardiac repair using regenerating neonatal heart tissue-derived extracellular vesicles

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 () and Benzhi Cai ()
Additional contact information
Hanjing Li: Harbin Medical University
Yining Liu: Harbin Medical University
Yuqing Lin: Harbin Medical University
Sijia Li: Harbin Medical University
Chenlu Liu: Harbin Institute of Technology
Ao Cai: Harbin Medical University
Wei Li: Harbin Medical University
Wanyu Zhang: Harbin Medical University
Xinlu Gao: Harbin Medical University
Zhongyu Ren: Harbin Medical University
Haoyu Ji: Harbin Medical University
Yang Yu: Harbin Medical University
Xiuxiu Wang: Harbin Medical University
Wenya Ma: Harbin Medical University
Ning Wang: Harbin Medical University
Dan Zhao: Harbin Medical University
Tianlong Li: Harbin Institute of Technology
Yu Liu: Harbin Medical University
Benzhi Cai: Harbin Medical University

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-56384-x

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