Sustained release of miR-21 carried by mesenchymal stem cell-derived exosomes from GelMA microspheres inhibits ovarian granulosa cell apoptosis in premature ovarian insufficiency
Background: Premature ovarian insufficiency (POI) refers to the severe decline or failure of ovarian function in women younger than 40 years of age. It is a serious hazard to women's physical and mental health, but current treatment options are limited. Mesenchymal stem cell-derived exosomes (M...
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Elsevier
2025-04-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006425000274 |
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| author | Xiaofei Zhang Linzi Ma Xiaotong Liu Xingyu Zhou Ao Wang Yunhui Lai Jun Zhang Ying Li Shiling Chen |
| author_facet | Xiaofei Zhang Linzi Ma Xiaotong Liu Xingyu Zhou Ao Wang Yunhui Lai Jun Zhang Ying Li Shiling Chen |
| author_sort | Xiaofei Zhang |
| collection | DOAJ |
| description | Background: Premature ovarian insufficiency (POI) refers to the severe decline or failure of ovarian function in women younger than 40 years of age. It is a serious hazard to women's physical and mental health, but current treatment options are limited. Mesenchymal stem cell-derived exosomes (MSC-Exo) exhibit promising potential as a therapeutic approach for POI. However, their clinical application is hindered by their instability and low long-term retention rate in vivo. Methods and results: In this study, miR-21 was identified as the predominant miRNA with low-expression in follicular fluid exosomes of POI patients and was shown to possess antiapoptotic activity. Next, we loaded miR-21 agomir to MSC-Exo to form Agomir21-Exo, which significantly reversed the apoptosis of granulosa cells in vitro. Moreover, we successfully developed GelMA hydrogel microspheres for encapsulating Agomir21-Exo through microfluidic technology, named GelMA-Ag21Exo, which had good injectability and significantly enhanced the stability and long-term retention of Agomir21-Exo in mice through sustained release. The release of Agomir21-Exo from GelMA-Ag21Exo notably alleviated the apoptosis of ovarian granulosa cells and improved the ovarian reserve and fertility in POI mice. Conclusion: Our findings illustrate that activating miR-21 through Agomir21-Exo could improve the function of ovarian granulosa cells. The GelMA-Ag21Exo enhanced the exosome-based therapeutic efficacy of the Agomir21-Exo in vivo. These findings provide a novel and promising treatment strategy for POI patients. |
| format | Article |
| id | doaj-art-c619c342e4a847f6a5efb2061e868ac2 |
| institution | Kabale University |
| issn | 2590-0064 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj-art-c619c342e4a847f6a5efb2061e868ac22025-01-24T04:45:36ZengElsevierMaterials Today Bio2590-00642025-04-0131101469Sustained release of miR-21 carried by mesenchymal stem cell-derived exosomes from GelMA microspheres inhibits ovarian granulosa cell apoptosis in premature ovarian insufficiencyXiaofei Zhang0Linzi Ma1Xiaotong Liu2Xingyu Zhou3Ao Wang4Yunhui Lai5Jun Zhang6Ying Li7Shiling Chen8Center for Reproductive Medicine, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, ChinaCenter for Reproductive Medicine, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, ChinaCenter for Reproductive Medicine, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, ChinaCenter for Reproductive Medicine, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, ChinaCenter for Reproductive Medicine, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, ChinaCenter for Reproductive Medicine, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, ChinaCenter for Reproductive Medicine, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, ChinaCenter for Reproductive Medicine, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, ChinaCorresponding author. Center for Reproductive Medicine, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, 1838th North Guangzhou Avenue, Guangzhou, 510515, China.; Center for Reproductive Medicine, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, ChinaBackground: Premature ovarian insufficiency (POI) refers to the severe decline or failure of ovarian function in women younger than 40 years of age. It is a serious hazard to women's physical and mental health, but current treatment options are limited. Mesenchymal stem cell-derived exosomes (MSC-Exo) exhibit promising potential as a therapeutic approach for POI. However, their clinical application is hindered by their instability and low long-term retention rate in vivo. Methods and results: In this study, miR-21 was identified as the predominant miRNA with low-expression in follicular fluid exosomes of POI patients and was shown to possess antiapoptotic activity. Next, we loaded miR-21 agomir to MSC-Exo to form Agomir21-Exo, which significantly reversed the apoptosis of granulosa cells in vitro. Moreover, we successfully developed GelMA hydrogel microspheres for encapsulating Agomir21-Exo through microfluidic technology, named GelMA-Ag21Exo, which had good injectability and significantly enhanced the stability and long-term retention of Agomir21-Exo in mice through sustained release. The release of Agomir21-Exo from GelMA-Ag21Exo notably alleviated the apoptosis of ovarian granulosa cells and improved the ovarian reserve and fertility in POI mice. Conclusion: Our findings illustrate that activating miR-21 through Agomir21-Exo could improve the function of ovarian granulosa cells. The GelMA-Ag21Exo enhanced the exosome-based therapeutic efficacy of the Agomir21-Exo in vivo. These findings provide a novel and promising treatment strategy for POI patients.http://www.sciencedirect.com/science/article/pii/S2590006425000274ExosomesMesenchymal stem cellGelMA hydrogelOvarian granulosa cellsPremature ovarian insufficiency |
| spellingShingle | Xiaofei Zhang Linzi Ma Xiaotong Liu Xingyu Zhou Ao Wang Yunhui Lai Jun Zhang Ying Li Shiling Chen Sustained release of miR-21 carried by mesenchymal stem cell-derived exosomes from GelMA microspheres inhibits ovarian granulosa cell apoptosis in premature ovarian insufficiency Materials Today Bio Exosomes Mesenchymal stem cell GelMA hydrogel Ovarian granulosa cells Premature ovarian insufficiency |
| title | Sustained release of miR-21 carried by mesenchymal stem cell-derived exosomes from GelMA microspheres inhibits ovarian granulosa cell apoptosis in premature ovarian insufficiency |
| title_full | Sustained release of miR-21 carried by mesenchymal stem cell-derived exosomes from GelMA microspheres inhibits ovarian granulosa cell apoptosis in premature ovarian insufficiency |
| title_fullStr | Sustained release of miR-21 carried by mesenchymal stem cell-derived exosomes from GelMA microspheres inhibits ovarian granulosa cell apoptosis in premature ovarian insufficiency |
| title_full_unstemmed | Sustained release of miR-21 carried by mesenchymal stem cell-derived exosomes from GelMA microspheres inhibits ovarian granulosa cell apoptosis in premature ovarian insufficiency |
| title_short | Sustained release of miR-21 carried by mesenchymal stem cell-derived exosomes from GelMA microspheres inhibits ovarian granulosa cell apoptosis in premature ovarian insufficiency |
| title_sort | sustained release of mir 21 carried by mesenchymal stem cell derived exosomes from gelma microspheres inhibits ovarian granulosa cell apoptosis in premature ovarian insufficiency |
| topic | Exosomes Mesenchymal stem cell GelMA hydrogel Ovarian granulosa cells Premature ovarian insufficiency |
| url | http://www.sciencedirect.com/science/article/pii/S2590006425000274 |
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