Mesenchymal Stem Cells with Simultaneous Overexpression of GPX3 and CD47 for the Treatment of Drug-Induced Acute Liver Injury
The liver, as the largest metabolic and detoxification organ in mammals, metabolizes approximately 80–90% of drugs. However, drug-induced liver injury (DILI) is common and driven by factors such as individual variability, differences in liver metabolism, and improper drug use. Mesenchymal stem cells...
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MDPI AG
2025-02-01
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| Series: | Veterinary Sciences |
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| Online Access: | https://www.mdpi.com/2306-7381/12/2/149 |
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| author | Yuanxiang Jing Balun Li Aili Aierken Zengyu Zhang Dongyao Han Zixi Lin Jiaqi Gao Hongkai Tian Jinlian Hua |
| author_facet | Yuanxiang Jing Balun Li Aili Aierken Zengyu Zhang Dongyao Han Zixi Lin Jiaqi Gao Hongkai Tian Jinlian Hua |
| author_sort | Yuanxiang Jing |
| collection | DOAJ |
| description | The liver, as the largest metabolic and detoxification organ in mammals, metabolizes approximately 80–90% of drugs. However, drug-induced liver injury (DILI) is common and driven by factors such as individual variability, differences in liver metabolism, and improper drug use. Mesenchymal stem cells (MSCs), with their self-renewal and multipotent differentiation capabilities, offer therapeutic potential, but face challenges such as limited proliferation and increased apoptosis during in vitro expansion. Although MSCs exhibit low immunogenicity, they are often cleared by the host immune system, which limits their survival and engraftment. Glutathione peroxidase 3 (GPX3) is a key antioxidant enzyme that reduces reactive oxygen species (ROS), protecting cells from oxidative damage. CD47, also known as integrin-associated protein (IAP), helps cells evade immune clearance by binding to signal regulatory protein alpha (SIRPα) on the immune cells. Here, we used an acetaminophen (APAP)-induced DILI mouse model to evaluate the therapeutic efficacy of intravenously infused MSCs overexpressing GPX3 and CD47. Compared to unmodified MSCs, modified MSCs showed improved survival, reduced liver inflammation, and alleviated oxidative damage, offering enhanced protection against APAP-induced DILI. |
| format | Article |
| id | doaj-art-f5e5c5de72bf46e29ea1eb23fcdda6cf |
| institution | DOAJ |
| issn | 2306-7381 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Veterinary Sciences |
| spelling | doaj-art-f5e5c5de72bf46e29ea1eb23fcdda6cf2025-08-20T02:45:39ZengMDPI AGVeterinary Sciences2306-73812025-02-0112214910.3390/vetsci12020149Mesenchymal Stem Cells with Simultaneous Overexpression of GPX3 and CD47 for the Treatment of Drug-Induced Acute Liver InjuryYuanxiang Jing0Balun Li1Aili Aierken2Zengyu Zhang3Dongyao Han4Zixi Lin5Jiaqi Gao6Hongkai Tian7Jinlian Hua8College of Veterinary Medicine, Shanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling 712100, ChinaCollege of Veterinary Medicine, Shanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling 712100, ChinaCollege of Veterinary Medicine, Shanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling 712100, ChinaCollege of Veterinary Medicine, Shanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling 712100, ChinaCollege of Veterinary Medicine, Shanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling 712100, ChinaCollege of Veterinary Medicine, Shanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling 712100, ChinaCollege of Veterinary Medicine, Shanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling 712100, ChinaCollege of Veterinary Medicine, Shanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling 712100, ChinaCollege of Veterinary Medicine, Shanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling 712100, ChinaThe liver, as the largest metabolic and detoxification organ in mammals, metabolizes approximately 80–90% of drugs. However, drug-induced liver injury (DILI) is common and driven by factors such as individual variability, differences in liver metabolism, and improper drug use. Mesenchymal stem cells (MSCs), with their self-renewal and multipotent differentiation capabilities, offer therapeutic potential, but face challenges such as limited proliferation and increased apoptosis during in vitro expansion. Although MSCs exhibit low immunogenicity, they are often cleared by the host immune system, which limits their survival and engraftment. Glutathione peroxidase 3 (GPX3) is a key antioxidant enzyme that reduces reactive oxygen species (ROS), protecting cells from oxidative damage. CD47, also known as integrin-associated protein (IAP), helps cells evade immune clearance by binding to signal regulatory protein alpha (SIRPα) on the immune cells. Here, we used an acetaminophen (APAP)-induced DILI mouse model to evaluate the therapeutic efficacy of intravenously infused MSCs overexpressing GPX3 and CD47. Compared to unmodified MSCs, modified MSCs showed improved survival, reduced liver inflammation, and alleviated oxidative damage, offering enhanced protection against APAP-induced DILI.https://www.mdpi.com/2306-7381/12/2/149mesenchymal stem cells (MSCs)GPX3CD47drug-induced liver injury |
| spellingShingle | Yuanxiang Jing Balun Li Aili Aierken Zengyu Zhang Dongyao Han Zixi Lin Jiaqi Gao Hongkai Tian Jinlian Hua Mesenchymal Stem Cells with Simultaneous Overexpression of GPX3 and CD47 for the Treatment of Drug-Induced Acute Liver Injury Veterinary Sciences mesenchymal stem cells (MSCs) GPX3 CD47 drug-induced liver injury |
| title | Mesenchymal Stem Cells with Simultaneous Overexpression of GPX3 and CD47 for the Treatment of Drug-Induced Acute Liver Injury |
| title_full | Mesenchymal Stem Cells with Simultaneous Overexpression of GPX3 and CD47 for the Treatment of Drug-Induced Acute Liver Injury |
| title_fullStr | Mesenchymal Stem Cells with Simultaneous Overexpression of GPX3 and CD47 for the Treatment of Drug-Induced Acute Liver Injury |
| title_full_unstemmed | Mesenchymal Stem Cells with Simultaneous Overexpression of GPX3 and CD47 for the Treatment of Drug-Induced Acute Liver Injury |
| title_short | Mesenchymal Stem Cells with Simultaneous Overexpression of GPX3 and CD47 for the Treatment of Drug-Induced Acute Liver Injury |
| title_sort | mesenchymal stem cells with simultaneous overexpression of gpx3 and cd47 for the treatment of drug induced acute liver injury |
| topic | mesenchymal stem cells (MSCs) GPX3 CD47 drug-induced liver injury |
| url | https://www.mdpi.com/2306-7381/12/2/149 |
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