Andrographolide protects bone marrow mesenchymal stem cells against glucose and serum deprivation under hypoxia via the NRF2 signaling pathway
Abstract Background Bone marrow mesenchymal stem cell (BMSCs) therapy is an important cell transplantation strategy in the regenerative medicine field. However, a severely ischemic microenvironment, such as nutrient depletion and hypoxia, causes a lower survival rate of transplanted BMSCs, limiting...
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BMC
2022-07-01
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Series: | Stem Cell Research & Therapy |
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Online Access: | https://doi.org/10.1186/s13287-022-03016-6 |
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author | Yanting Sun Hao Xu Bin Tan Qin Yi Huiwen Liu Tangtian Chen Han Xiang Rui Wang Qiumin Xie Jie Tian Jing Zhu |
author_facet | Yanting Sun Hao Xu Bin Tan Qin Yi Huiwen Liu Tangtian Chen Han Xiang Rui Wang Qiumin Xie Jie Tian Jing Zhu |
author_sort | Yanting Sun |
collection | DOAJ |
description | Abstract Background Bone marrow mesenchymal stem cell (BMSCs) therapy is an important cell transplantation strategy in the regenerative medicine field. However, a severely ischemic microenvironment, such as nutrient depletion and hypoxia, causes a lower survival rate of transplanted BMSCs, limiting the application of BMSCs. Therefore, improving BMSCs viability in adverse microenvironments is an important means to improve the effectiveness of BMSCs therapy. Objective To illustrate the protective effect of andrographolide (AG) against glucose and serum deprivation under hypoxia (1% O2) (GSDH)-induced cell injury in BMSCs and investigate the possible underlying mechanisms. Methods An in vitro primary rat BMSCs cell injury model was established by GSDH, and cellular viability, proliferation and apoptosis were observed after AG treatment under GSDH. Reactive oxygen species levels and oxidative stress-related genes and proteins were measured by flow cytometry, RT-qPCR and Western blotting. Mitochondrial morphology, function and number were further assessed by laser confocal microscopy and flow cytometry. Results AG protected BMSCs against GSDH-induced cell injury, as indicated by increases in cell viability and proliferation and mitochondrial number and decreases in apoptosis and oxidative stress. The metabolic status of BMSCs was changed from glycolysis to oxidative phosphorylation to increase the ATP supply. We further observed that the NRF2 pathway was activated by AG, and treatment of BMSCs with a specific NRF2 inhibitor (ML385) blocked the protective effect of AG. Conclusion Our results suggest that AG is a promising agent to improve the therapeutic effect of BMSCs. |
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spelling | doaj.art-c0df81f62dbe46098b0579ed67d913682022-12-22T03:04:55ZengBMCStem Cell Research & Therapy1757-65122022-07-0113111810.1186/s13287-022-03016-6Andrographolide protects bone marrow mesenchymal stem cells against glucose and serum deprivation under hypoxia via the NRF2 signaling pathwayYanting Sun0Hao Xu1Bin Tan2Qin Yi3Huiwen Liu4Tangtian Chen5Han Xiang6Rui Wang7Qiumin Xie8Jie Tian9Jing Zhu10Department of Pediatric Research Institute, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of PediatricsDepartment of Pediatric Research Institute, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of PediatricsDepartment of Pediatric Research Institute, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of PediatricsDepartment of Pediatric Research Institute, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of PediatricsDepartment of Pediatric Research Institute, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of PediatricsDepartment of Pediatric Research Institute, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of PediatricsDepartment of Pediatric Research Institute, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of PediatricsDepartment of Pediatric Research Institute, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of PediatricsDepartment of Pediatric Research Institute, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of PediatricsDepartment of Pediatric Research Institute, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of PediatricsDepartment of Pediatric Research Institute, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of PediatricsAbstract Background Bone marrow mesenchymal stem cell (BMSCs) therapy is an important cell transplantation strategy in the regenerative medicine field. However, a severely ischemic microenvironment, such as nutrient depletion and hypoxia, causes a lower survival rate of transplanted BMSCs, limiting the application of BMSCs. Therefore, improving BMSCs viability in adverse microenvironments is an important means to improve the effectiveness of BMSCs therapy. Objective To illustrate the protective effect of andrographolide (AG) against glucose and serum deprivation under hypoxia (1% O2) (GSDH)-induced cell injury in BMSCs and investigate the possible underlying mechanisms. Methods An in vitro primary rat BMSCs cell injury model was established by GSDH, and cellular viability, proliferation and apoptosis were observed after AG treatment under GSDH. Reactive oxygen species levels and oxidative stress-related genes and proteins were measured by flow cytometry, RT-qPCR and Western blotting. Mitochondrial morphology, function and number were further assessed by laser confocal microscopy and flow cytometry. Results AG protected BMSCs against GSDH-induced cell injury, as indicated by increases in cell viability and proliferation and mitochondrial number and decreases in apoptosis and oxidative stress. The metabolic status of BMSCs was changed from glycolysis to oxidative phosphorylation to increase the ATP supply. We further observed that the NRF2 pathway was activated by AG, and treatment of BMSCs with a specific NRF2 inhibitor (ML385) blocked the protective effect of AG. Conclusion Our results suggest that AG is a promising agent to improve the therapeutic effect of BMSCs.https://doi.org/10.1186/s13287-022-03016-6BMSCsNRF2AndrographolideApoptosisOxidative stress |
spellingShingle | Yanting Sun Hao Xu Bin Tan Qin Yi Huiwen Liu Tangtian Chen Han Xiang Rui Wang Qiumin Xie Jie Tian Jing Zhu Andrographolide protects bone marrow mesenchymal stem cells against glucose and serum deprivation under hypoxia via the NRF2 signaling pathway Stem Cell Research & Therapy BMSCs NRF2 Andrographolide Apoptosis Oxidative stress |
title | Andrographolide protects bone marrow mesenchymal stem cells against glucose and serum deprivation under hypoxia via the NRF2 signaling pathway |
title_full | Andrographolide protects bone marrow mesenchymal stem cells against glucose and serum deprivation under hypoxia via the NRF2 signaling pathway |
title_fullStr | Andrographolide protects bone marrow mesenchymal stem cells against glucose and serum deprivation under hypoxia via the NRF2 signaling pathway |
title_full_unstemmed | Andrographolide protects bone marrow mesenchymal stem cells against glucose and serum deprivation under hypoxia via the NRF2 signaling pathway |
title_short | Andrographolide protects bone marrow mesenchymal stem cells against glucose and serum deprivation under hypoxia via the NRF2 signaling pathway |
title_sort | andrographolide protects bone marrow mesenchymal stem cells against glucose and serum deprivation under hypoxia via the nrf2 signaling pathway |
topic | BMSCs NRF2 Andrographolide Apoptosis Oxidative stress |
url | https://doi.org/10.1186/s13287-022-03016-6 |
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