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; Benzhi Cai

doi:10.1038/s41467-025-56384-x

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^*
, Benzhi Cai^*

^*Corresponding author for this work

School of Mechatronics Engineering

Harbin Medical University
Harbin Institute of Technology

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

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.

Original language	English
Article number	1292
Journal	Nature Communications
Volume	16
Issue number	1
DOIs	https://doi.org/10.1038/s41467-025-56384-x
State	Published - Dec 2025

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title = "Cardiac repair using regenerating neonatal heart tissue-derived extracellular vesicles",

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.",

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

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doi = "10.1038/s41467-025-56384-x",

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AU - Li, Hanjing

AU - Liu, Yining

AU - Lin, Yuqing

AU - Li, Sijia

AU - Liu, Chenlu

AU - Cai, Ao

AU - Li, Wei

AU - Zhang, Wanyu

AU - Gao, Xinlu

AU - Ren, Zhongyu

AU - Ji, Haoyu

AU - Yu, Yang

AU - Wang, Xiuxiu

AU - Ma, Wenya

AU - Wang, Ning

AU - Zhao, Dan

AU - Li, Tianlong

AU - Liu, Yu

AU - Cai, Benzhi

PY - 2025/12

Y1 - 2025/12

N2 - 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.

AB - 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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DO - 10.1038/s41467-025-56384-x

M3 - 文章

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SN - 2041-1723

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JO - Nature Communications

JF - Nature Communications

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ER -

Cardiac repair using regenerating neonatal heart tissue-derived extracellular vesicles

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