Genetically engineered MSC-derived hybrid cellular vesicles for ROS-scavenging and mitochondrial homeostasis in hepatic ischemia-reperfusion injury
Hepatic ischemia-reperfusion injury (IRI) poses a significant clinical challenge in liver surgery and transplantation, primarily mediated through oxidative stress, mitochondrial dysfunction, and inflammatory activation. Herein, we developed SOD2-Res@CVs, an engineered vesicular platform combining SO...
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Elsevier
2025-10-01
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| author | Pu Shen Kaijun Huang Xuanlin Zhang Guiyuan Yin Meiting Qin Hua Ma Zhijin Fan Yuhui Liao |
| author_facet | Pu Shen Kaijun Huang Xuanlin Zhang Guiyuan Yin Meiting Qin Hua Ma Zhijin Fan Yuhui Liao |
| author_sort | Pu Shen |
| collection | DOAJ |
| description | Hepatic ischemia-reperfusion injury (IRI) poses a significant clinical challenge in liver surgery and transplantation, primarily mediated through oxidative stress, mitochondrial dysfunction, and inflammatory activation. Herein, we developed SOD2-Res@CVs, an engineered vesicular platform combining SOD2-overexpressing mesenchymal stem cell-derived vesicles with liver-targeted and ROS-responsive resveratrol (Res)-loaded liposomes for multi-mechanistic intervention. In vivo imaging demonstrated that SOD2-Res@CVs selectively accumulated in IRI-damaged hepatic tissues. Within oxidative stress microenvironments, the system exhibited responsive liberation of SOD2 and resveratrol, which cooperatively mitigated oxidative damage through redox homeostasis modulation - evidenced by reduced lipid peroxidation (MDA suppression) and enhanced antioxidant defense (GSH/SOD2 upregulation). This therapeutic cascade facilitated mitochondrial structural and functional restoration via multiple pathways: Resveratrol specifically activated PINK1-mediated mitophagy, as confirmed by increased LC3 and beclin-1 expression, thereby promoting selective clearance of depolarized mitochondria. Comparative analyses revealed SOD2-Res@CVs' superior therapeutic efficacy over individual components in histological recovery and organ function preservation. Transcriptomic profiling further validated the system's multi-target regulatory capacity, highlighting its concurrent suppression of oxidative stress pathways, mitigation of inflammatory signaling, and improvement of mitochondrial bioenergetics during IRI progression. This study establishes SOD2-Res@CVs as a multifunctional nanotherapeutic strategy that harmonizes spatial targeting with pathological microenvironment responsiveness and a promising approach for liver protection in transplantation. |
| format | Article |
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| institution | Kabale University |
| issn | 2590-0064 |
| language | English |
| publishDate | 2025-10-01 |
| publisher | Elsevier |
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| spelling | doaj-art-f34434f67f5f4bcbab3b2dfd37ff1a5c2025-08-23T04:48:57ZengElsevierMaterials Today Bio2590-00642025-10-013410221510.1016/j.mtbio.2025.102215Genetically engineered MSC-derived hybrid cellular vesicles for ROS-scavenging and mitochondrial homeostasis in hepatic ischemia-reperfusion injuryPu Shen0Kaijun Huang1Xuanlin Zhang2Guiyuan Yin3Meiting Qin4Hua Ma5Zhijin Fan6Yuhui Liao7Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, ChinaDepartment of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China; Corresponding authors.Huaihe Hospital of Henan University, Kaifeng, 475000, ChinaInstitute for Engineering Medicine, Kunming Medical University, Kunming, 650500, ChinaOrgan Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, ChinaInstitute for Engineering Medicine, Kunming Medical University, Kunming, 650500, China; Corresponding author.Institute for Engineering Medicine, Kunming Medical University, Kunming, 650500, China; Corresponding authors.Institute for Engineering Medicine, Kunming Medical University, Kunming, 650500, China; Corresponding author.Hepatic ischemia-reperfusion injury (IRI) poses a significant clinical challenge in liver surgery and transplantation, primarily mediated through oxidative stress, mitochondrial dysfunction, and inflammatory activation. Herein, we developed SOD2-Res@CVs, an engineered vesicular platform combining SOD2-overexpressing mesenchymal stem cell-derived vesicles with liver-targeted and ROS-responsive resveratrol (Res)-loaded liposomes for multi-mechanistic intervention. In vivo imaging demonstrated that SOD2-Res@CVs selectively accumulated in IRI-damaged hepatic tissues. Within oxidative stress microenvironments, the system exhibited responsive liberation of SOD2 and resveratrol, which cooperatively mitigated oxidative damage through redox homeostasis modulation - evidenced by reduced lipid peroxidation (MDA suppression) and enhanced antioxidant defense (GSH/SOD2 upregulation). This therapeutic cascade facilitated mitochondrial structural and functional restoration via multiple pathways: Resveratrol specifically activated PINK1-mediated mitophagy, as confirmed by increased LC3 and beclin-1 expression, thereby promoting selective clearance of depolarized mitochondria. Comparative analyses revealed SOD2-Res@CVs' superior therapeutic efficacy over individual components in histological recovery and organ function preservation. Transcriptomic profiling further validated the system's multi-target regulatory capacity, highlighting its concurrent suppression of oxidative stress pathways, mitigation of inflammatory signaling, and improvement of mitochondrial bioenergetics during IRI progression. This study establishes SOD2-Res@CVs as a multifunctional nanotherapeutic strategy that harmonizes spatial targeting with pathological microenvironment responsiveness and a promising approach for liver protection in transplantation.http://www.sciencedirect.com/science/article/pii/S2590006425007859Hepatic ischemia-reperfusion injuryCellular vesiclesMesenchymal stem cellMitochondrial homeostasisResveratrol |
| spellingShingle | Pu Shen Kaijun Huang Xuanlin Zhang Guiyuan Yin Meiting Qin Hua Ma Zhijin Fan Yuhui Liao Genetically engineered MSC-derived hybrid cellular vesicles for ROS-scavenging and mitochondrial homeostasis in hepatic ischemia-reperfusion injury Materials Today Bio Hepatic ischemia-reperfusion injury Cellular vesicles Mesenchymal stem cell Mitochondrial homeostasis Resveratrol |
| title | Genetically engineered MSC-derived hybrid cellular vesicles for ROS-scavenging and mitochondrial homeostasis in hepatic ischemia-reperfusion injury |
| title_full | Genetically engineered MSC-derived hybrid cellular vesicles for ROS-scavenging and mitochondrial homeostasis in hepatic ischemia-reperfusion injury |
| title_fullStr | Genetically engineered MSC-derived hybrid cellular vesicles for ROS-scavenging and mitochondrial homeostasis in hepatic ischemia-reperfusion injury |
| title_full_unstemmed | Genetically engineered MSC-derived hybrid cellular vesicles for ROS-scavenging and mitochondrial homeostasis in hepatic ischemia-reperfusion injury |
| title_short | Genetically engineered MSC-derived hybrid cellular vesicles for ROS-scavenging and mitochondrial homeostasis in hepatic ischemia-reperfusion injury |
| title_sort | genetically engineered msc derived hybrid cellular vesicles for ros scavenging and mitochondrial homeostasis in hepatic ischemia reperfusion injury |
| topic | Hepatic ischemia-reperfusion injury Cellular vesicles Mesenchymal stem cell Mitochondrial homeostasis Resveratrol |
| url | http://www.sciencedirect.com/science/article/pii/S2590006425007859 |
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