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. H...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56384-x |
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| author | 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 |
| author_facet | 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 |
| author_sort | Hanjing Li |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-654c2da1b25d4f1a87f5649827216f78 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-654c2da1b25d4f1a87f5649827216f782025-02-09T12:46:03ZengNature PortfolioNature Communications2041-17232025-02-0116111810.1038/s41467-025-56384-xCardiac repair using regenerating neonatal heart tissue-derived extracellular vesiclesHanjing Li0Yining Liu1Yuqing Lin2Sijia Li3Chenlu Liu4Ao Cai5Wei Li6Wanyu Zhang7Xinlu Gao8Zhongyu Ren9Haoyu Ji10Yang Yu11Xiuxiu Wang12Wenya Ma13Ning Wang14Dan Zhao15Tianlong Li16Yu Liu17Benzhi Cai18Department of Pharmacy at the Second Affiliated Hospital (National Key Laboratory of Frigid Zone Cardiovascular Diseases, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical UniversityDepartment of Pharmacy at the Second Affiliated Hospital (National Key Laboratory of Frigid Zone Cardiovascular Diseases, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical UniversityDepartment of Pharmacy at the Second Affiliated Hospital (National Key Laboratory of Frigid Zone Cardiovascular Diseases, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical UniversityDepartment of Pharmacy at the Second Affiliated Hospital (National Key Laboratory of Frigid Zone Cardiovascular Diseases, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical UniversityState Key Laboratory of Robotics and System, Harbin Institute of TechnologyDepartment of Pharmacy at the Second Affiliated Hospital (National Key Laboratory of Frigid Zone Cardiovascular Diseases, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical UniversityDepartment of Pharmacy at the Second Affiliated Hospital (National Key Laboratory of Frigid Zone Cardiovascular Diseases, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical UniversityDepartment of Pharmacy at the Second Affiliated Hospital (National Key Laboratory of Frigid Zone Cardiovascular Diseases, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical UniversityDepartment of Pharmacy at the Second Affiliated Hospital (National Key Laboratory of Frigid Zone Cardiovascular Diseases, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical UniversityDepartment of Pharmacy at the Second Affiliated Hospital (National Key Laboratory of Frigid Zone Cardiovascular Diseases, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical UniversityDepartment of Pharmacy at the Second Affiliated Hospital (National Key Laboratory of Frigid Zone Cardiovascular Diseases, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical UniversityDepartment of Pharmacy at the Second Affiliated Hospital (National Key Laboratory of Frigid Zone Cardiovascular Diseases, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical UniversityDepartment of Pharmacy at the Second Affiliated Hospital (National Key Laboratory of Frigid Zone Cardiovascular Diseases, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical UniversityDepartment of Pharmacy at the Second Affiliated Hospital (National Key Laboratory of Frigid Zone Cardiovascular Diseases, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical UniversityDepartment of Pharmacology at College of Pharmacy, Harbin Medical UniversityDepartment of Pharmacy at the Second Affiliated Hospital (National Key Laboratory of Frigid Zone Cardiovascular Diseases, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical UniversityState Key Laboratory of Robotics and System, Harbin Institute of TechnologyDepartment of Laboratory Medicine at the Fourth Affiliated Hospital, Harbin Medical UniversityDepartment of Pharmacy at the Second Affiliated Hospital (National Key Laboratory of Frigid Zone Cardiovascular Diseases, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical UniversityAbstract 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.https://doi.org/10.1038/s41467-025-56384-x |
| spellingShingle | 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 Cardiac repair using regenerating neonatal heart tissue-derived extracellular vesicles Nature Communications |
| title | Cardiac repair using regenerating neonatal heart tissue-derived extracellular vesicles |
| title_full | Cardiac repair using regenerating neonatal heart tissue-derived extracellular vesicles |
| title_fullStr | Cardiac repair using regenerating neonatal heart tissue-derived extracellular vesicles |
| title_full_unstemmed | Cardiac repair using regenerating neonatal heart tissue-derived extracellular vesicles |
| title_short | Cardiac repair using regenerating neonatal heart tissue-derived extracellular vesicles |
| title_sort | cardiac repair using regenerating neonatal heart tissue derived extracellular vesicles |
| url | https://doi.org/10.1038/s41467-025-56384-x |
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