Trained human bone marrow mesenchymal stem cells restore tissue immuno-microenvironment in fulminant hepatic failure mice
Abstract Background Trained immunity with human bone marrow mesenchymal stem cells (hBMSC) is a promising approach to liver regeneration. This study aimed to clarify the trained-hBMSC (T-hBMSC) in restoring tissue immuno-microenvironment in fulminant hepatic failure (FHF) mice. Methods hBMSC trained...
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BMC
2025-08-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13287-025-04540-x |
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| author | Bingqi Li Xiaofei Zeng Jing Jiang Qian Zhou Li Tong Xi Liang Jiaojiao Xin Xi Chen Xiao Wu Yuheng Kong Shiwen Ma Jinjin Luo Wei Qiang Bing Zhu Xinhua Luo Jun Li Dongyan Shi |
| author_facet | Bingqi Li Xiaofei Zeng Jing Jiang Qian Zhou Li Tong Xi Liang Jiaojiao Xin Xi Chen Xiao Wu Yuheng Kong Shiwen Ma Jinjin Luo Wei Qiang Bing Zhu Xinhua Luo Jun Li Dongyan Shi |
| author_sort | Bingqi Li |
| collection | DOAJ |
| description | Abstract Background Trained immunity with human bone marrow mesenchymal stem cells (hBMSC) is a promising approach to liver regeneration. This study aimed to clarify the trained-hBMSC (T-hBMSC) in restoring tissue immuno-microenvironment in fulminant hepatic failure (FHF) mice. Methods hBMSC trained with tumor necrosis factor-α and interferon-γ were phenotypically characterized in vitro. FHF mouse models were established in male Balb/c mice via tail vein injection of concanavalin A. The therapeutic potential of T-hBMSC was evaluated through transplantation into FHF mice. Transcriptomic analysis was performed to elucidate the mechanism of liver regeneration post-transplantation of T-hBMSC. Results T-hBMSC with the characteristics of trilineage differentiation potential showed that pro-inflammatory (IL1β, IL8, both p < 0.0001) and immunoregulatory genes (PDL1, IDO1, both p < 0.0001) were significantly upregulated compared to untrained-hBMSC (UT-hBMSC). Time-trajectory analysis revealed downregulation of pro-inflammatory genes (IL6, IL8, and IL1α) and upregulation of immunomodulatory genes (IDO1) in T-hBMSC upon mimic-stimulation, characterized by distinct transcriptional programs. The liver function (ALT, AST) and inflammatory cytokines (IL6, MCP1, both p < 0.01) levels were significantly improved in the T-hBMSC-treated mice. The survival status of the T-hBMSC group was superior to the UT-hBMSC group, although there was no statistical significance. Histological analysis confirmed reduced necrosis and fewer infiltrating CD45+ immune cells in the T-hBMSC-treated mice. Significant downregulation of immune response (TNF & IL-17 signaling pathways and neutrophil chemotaxis) and upregulation of metabolic pathways were observed in the T-hBMSC group, associated with enhanced liver regeneration. The proportion of anti-inflammatory F4/80+CD163+ macrophages was increased in the liver of T-hBMSC group. Conclusion T-hBMSC exhibited enhanced immunomodulation, effectively rescuing liver failure and reducing inflammation via restoring the immune-microenvironment. These findings highlighted the potential of trained immunity as a novel strategy for the treatment of liver failure. Graphical Abstract |
| format | Article |
| id | doaj-art-a41fca5d6f044cce9f8ed22cad78c816 |
| institution | Kabale University |
| issn | 1757-6512 |
| language | English |
| publishDate | 2025-08-01 |
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| series | Stem Cell Research & Therapy |
| spelling | doaj-art-a41fca5d6f044cce9f8ed22cad78c8162025-08-20T03:46:00ZengBMCStem Cell Research & Therapy1757-65122025-08-0116111710.1186/s13287-025-04540-xTrained human bone marrow mesenchymal stem cells restore tissue immuno-microenvironment in fulminant hepatic failure miceBingqi Li0Xiaofei Zeng1Jing Jiang2Qian Zhou3Li Tong4Xi Liang5Jiaojiao Xin6Xi Chen7Xiao Wu8Yuheng Kong9Shiwen Ma10Jinjin Luo11Wei Qiang12Bing Zhu13Xinhua Luo14Jun Li15Dongyan Shi16State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, China-Singapore Belt and Road Joint Laboratory on Infection Research and Drug Development, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of MedicineZunyi Medical UniversityState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, China-Singapore Belt and Road Joint Laboratory on Infection Research and Drug Development, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of MedicineState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, China-Singapore Belt and Road Joint Laboratory on Infection Research and Drug Development, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of MedicineNursing Department, The First Affiliated Hospital, Zhejiang University School of MedicineState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, China-Singapore Belt and Road Joint Laboratory on Infection Research and Drug Development, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of MedicineState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, China-Singapore Belt and Road Joint Laboratory on Infection Research and Drug Development, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Bioengineering, Imperial College LondonState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, China-Singapore Belt and Road Joint Laboratory on Infection Research and Drug Development, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of MedicineState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, China-Singapore Belt and Road Joint Laboratory on Infection Research and Drug Development, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of MedicineState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, China-Singapore Belt and Road Joint Laboratory on Infection Research and Drug Development, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of MedicineState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, China-Singapore Belt and Road Joint Laboratory on Infection Research and Drug Development, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of MedicineState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, China-Singapore Belt and Road Joint Laboratory on Infection Research and Drug Development, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Hepatology, Liver Vascular Disease Diagnosis And Treatment Center, The Fifth Medical Center of PLA General HospitalDepartment of Infectious Diseases, Guizhou Provincial People’s HospitalState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, China-Singapore Belt and Road Joint Laboratory on Infection Research and Drug Development, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of MedicineState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, China-Singapore Belt and Road Joint Laboratory on Infection Research and Drug Development, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of MedicineAbstract Background Trained immunity with human bone marrow mesenchymal stem cells (hBMSC) is a promising approach to liver regeneration. This study aimed to clarify the trained-hBMSC (T-hBMSC) in restoring tissue immuno-microenvironment in fulminant hepatic failure (FHF) mice. Methods hBMSC trained with tumor necrosis factor-α and interferon-γ were phenotypically characterized in vitro. FHF mouse models were established in male Balb/c mice via tail vein injection of concanavalin A. The therapeutic potential of T-hBMSC was evaluated through transplantation into FHF mice. Transcriptomic analysis was performed to elucidate the mechanism of liver regeneration post-transplantation of T-hBMSC. Results T-hBMSC with the characteristics of trilineage differentiation potential showed that pro-inflammatory (IL1β, IL8, both p < 0.0001) and immunoregulatory genes (PDL1, IDO1, both p < 0.0001) were significantly upregulated compared to untrained-hBMSC (UT-hBMSC). Time-trajectory analysis revealed downregulation of pro-inflammatory genes (IL6, IL8, and IL1α) and upregulation of immunomodulatory genes (IDO1) in T-hBMSC upon mimic-stimulation, characterized by distinct transcriptional programs. The liver function (ALT, AST) and inflammatory cytokines (IL6, MCP1, both p < 0.01) levels were significantly improved in the T-hBMSC-treated mice. The survival status of the T-hBMSC group was superior to the UT-hBMSC group, although there was no statistical significance. Histological analysis confirmed reduced necrosis and fewer infiltrating CD45+ immune cells in the T-hBMSC-treated mice. Significant downregulation of immune response (TNF & IL-17 signaling pathways and neutrophil chemotaxis) and upregulation of metabolic pathways were observed in the T-hBMSC group, associated with enhanced liver regeneration. The proportion of anti-inflammatory F4/80+CD163+ macrophages was increased in the liver of T-hBMSC group. Conclusion T-hBMSC exhibited enhanced immunomodulation, effectively rescuing liver failure and reducing inflammation via restoring the immune-microenvironment. These findings highlighted the potential of trained immunity as a novel strategy for the treatment of liver failure. Graphical Abstracthttps://doi.org/10.1186/s13287-025-04540-xTrained immunityBone marrow mesenchymal stem cellsImmune microenvironmentFulminant hepatic failure |
| spellingShingle | Bingqi Li Xiaofei Zeng Jing Jiang Qian Zhou Li Tong Xi Liang Jiaojiao Xin Xi Chen Xiao Wu Yuheng Kong Shiwen Ma Jinjin Luo Wei Qiang Bing Zhu Xinhua Luo Jun Li Dongyan Shi Trained human bone marrow mesenchymal stem cells restore tissue immuno-microenvironment in fulminant hepatic failure mice Stem Cell Research & Therapy Trained immunity Bone marrow mesenchymal stem cells Immune microenvironment Fulminant hepatic failure |
| title | Trained human bone marrow mesenchymal stem cells restore tissue immuno-microenvironment in fulminant hepatic failure mice |
| title_full | Trained human bone marrow mesenchymal stem cells restore tissue immuno-microenvironment in fulminant hepatic failure mice |
| title_fullStr | Trained human bone marrow mesenchymal stem cells restore tissue immuno-microenvironment in fulminant hepatic failure mice |
| title_full_unstemmed | Trained human bone marrow mesenchymal stem cells restore tissue immuno-microenvironment in fulminant hepatic failure mice |
| title_short | Trained human bone marrow mesenchymal stem cells restore tissue immuno-microenvironment in fulminant hepatic failure mice |
| title_sort | trained human bone marrow mesenchymal stem cells restore tissue immuno microenvironment in fulminant hepatic failure mice |
| topic | Trained immunity Bone marrow mesenchymal stem cells Immune microenvironment Fulminant hepatic failure |
| url | https://doi.org/10.1186/s13287-025-04540-x |
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