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Hao LS, Ji JX, Jiang MY, Song J, Chen PP, Zhan ZY, Miao XJ, Gao YY, Wang W, Liu T. Effects of changes in SHP2 expression on liver fibrosis by influencing the apoptosis of hepatic stellate cells. APMIS 2025; 133:e13487. [PMID: 39500724 DOI: 10.1111/apm.13487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Accepted: 10/21/2024] [Indexed: 12/18/2024]
Abstract
Accumulating research has revealed that src-homology domain 2-containing protein tyrosine phosphatase-2 (SHP2), an oncogenic protein tyrosine phosphatase, is associated with liver fibrosis. Currently, it is still unclear whether SHP2 affects liver fibrosis by influencing the apoptosis of hepatic stellate cells (HSC). In present study, we investigate effects of SHP2 expression changes on liver fibrosis, with special emphasis on the apoptosis of HSC. Using adenovirus vector, wild-type SHP2 gene and short hairpin RNA targeting SHP2 were introduced into rats with liver fibrosis and LX-2 cells in vitro. The expressions of type I and III collagen, pathological and functional changes, collagen deposition in rat liver and apoptosis of LX-2 cells were detected by immunohistochemical and HE staining, automated biochemical analyzer, Masson trichrome staining, and TUNEL. This study showed that overexpression of SHP2 exacerbated dysfunction, inflammatory damage, collagen deposition and increased expression of type I and III collagen in rat liver reduced apoptosis of LX-2 cells. On the contrary, low expression of SHP2 alleviated the aforementioned detection indicators of rats and promoted apoptosis of LX-2 cells. In conclusion, the downregulation of SHP2 expression alleviates liver fibrosis by inducing the apoptosis of HSC, while overexpressed SHP2 exacerbates liver fibrosis by inhibiting the apoptosis of HSC.
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Affiliation(s)
- Li-Sen Hao
- Department of Gastroenterology, Affiliated Hospital of North China University of Science and Technology, Tangshan, Hebei Province, China
| | - Jing-Xiu Ji
- Department of Gastroenterology, Affiliated Hospital of North China University of Science and Technology, Tangshan, Hebei Province, China
| | - Mei-Yu Jiang
- Department of Gastroenterology, Affiliated Hospital of North China University of Science and Technology, Tangshan, Hebei Province, China
| | - Jie Song
- Department of Gastroenterology, Affiliated Hospital of North China University of Science and Technology, Tangshan, Hebei Province, China
| | - Pan-Pan Chen
- Department of Gastroenterology, Affiliated Hospital of North China University of Science and Technology, Tangshan, Hebei Province, China
| | - Zong-Yuan Zhan
- Department of Gastroenterology, Affiliated Hospital of North China University of Science and Technology, Tangshan, Hebei Province, China
| | - Xiao-Jia Miao
- Department of Gastroenterology, Affiliated Hospital of North China University of Science and Technology, Tangshan, Hebei Province, China
| | - Ying-Ying Gao
- Department of Gastroenterology, Affiliated Hospital of North China University of Science and Technology, Tangshan, Hebei Province, China
| | - Wei Wang
- Department of Gastroenterology, Affiliated Hospital of North China University of Science and Technology, Tangshan, Hebei Province, China
| | - Tian Liu
- Department of Gastroenterology, Affiliated Hospital of North China University of Science and Technology, Tangshan, Hebei Province, China
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Wang X, Wang Y, Lu W, Qu J, Zhang Y, Ye J. Effectiveness and mechanisms of mesenchymal stem cell therapy in preclinical animal models of hepatic fibrosis: a systematic review and meta-analysis. Front Bioeng Biotechnol 2024; 12:1424253. [PMID: 39104627 PMCID: PMC11299041 DOI: 10.3389/fbioe.2024.1424253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2024] [Accepted: 06/26/2024] [Indexed: 08/07/2024] Open
Abstract
Background Liver damage due to long-term viral infection, alcohol consumption, autoimmune decline, and other factors could lead to the gradual development of liver fibrosis. Unfortunately, until now, there has been no effective treatment for liver fibrosis. Mesenchymal stem cells, as a promising new therapy for liver fibrosis, can slow the progression of fibrosis by migrating to the site of liver injury and by altering the microenvironment of the fibrotic area. Aim By including all relevant studies to date to comprehensively assess the efficacy of mesenchymal stem cells for the treatment of hepatic fibrosis and to explore considerations for clinical translation and therapeutic mechanisms. Methods Data sources included PubMed, Web of Science, Embase, and Cochrane Library, and were constructed until October 2023. Data for each study outcome indicator were extracted for comprehensive analysis. Results The overall meta-analysis showed that mesenchymal stem cells significantly improved liver function. Moreover, it inhibited the expression level of transforming growth factor-β [SMD = 4.21, 95% CI (3.02,5.40)], which in turn silenced hepatic stellate cells and significantly reduced the area of liver fibrosis [SMD = 3.61, 95% CI (1.41,5.81)]. Conclusion Several outcome indicators suggest that mesenchymal stem cells therapy is relatively reliable in the treatment of liver fibrosis. The therapeutic effect is cell dose-dependent over a range of doses, but not more effective at higher doses. Bone-marrow derived mesenchymal stem cells were more effective in treating liver fibrosis than mesenchymal stem cells from other sources. Systematic Review Registration Identifier CRD42022354768.
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Affiliation(s)
- Xuesong Wang
- Subcenter for Stem Cell Clinical Translation, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China
- School of Rehabilitation Medicine Gannan Medical University, Ganzhou, Jiangxi, China
- Ganzhou Key Laboratory of Stem Cell and Regenerative Medicine, Ganzhou, Jiangxi, China
| | - Yue Wang
- College of Nursing, Gannan Medical University, Ganzhou, Jiangxi, China
| | - Wenming Lu
- Subcenter for Stem Cell Clinical Translation, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China
- School of Rehabilitation Medicine Gannan Medical University, Ganzhou, Jiangxi, China
- Ganzhou Key Laboratory of Stem Cell and Regenerative Medicine, Ganzhou, Jiangxi, China
| | - Jiayang Qu
- Rehabilitation Assessment and Treatment Center, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Yang Zhang
- School of Rehabilitation Medicine Gannan Medical University, Ganzhou, Jiangxi, China
| | - Junsong Ye
- Subcenter for Stem Cell Clinical Translation, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China
- Ganzhou Key Laboratory of Stem Cell and Regenerative Medicine, Ganzhou, Jiangxi, China
- Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, Jiangxi, China
- Jiangxi Provincal Key Laboratory of Tissue Engineering, Gannan Medical University, Ganzhou, Jiangxi, China
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Zhang X, Liu M, Wang Z, Wang P, Kong L, Wu J, Wu W, Ma L, Jiang S, Ren W, Du L, Ma W, Liu X. A review of the botany, phytochemistry, pharmacology, synthetic biology and comprehensive utilization of Silybum marianum. Front Pharmacol 2024; 15:1417655. [PMID: 39055491 PMCID: PMC11269164 DOI: 10.3389/fphar.2024.1417655] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Accepted: 06/20/2024] [Indexed: 07/27/2024] Open
Abstract
Silybum marianum (L.) Gaertn, a herbaceous plant with a long history in traditional medicine for the treatment of hepatobiliary diseases, particularly in Europe, which has attracted attention for its remarkable therapeutic effect. This review systematically summarizes the research progress in the botany, phytochemistry, pharmacology, comprehensive utilization and synthetic biology of S. marianum. Up to now, more than 20 types of flavonolignan components have been isolated from S. marianum. In addition, the rearch on fatty acids and triterpenoids is also constantly improving. Among them, silybin is the most active compound in flavonolignans components. Its pharmacological effects in vivo and in vitro include anti-inflammatory, antioxidant, anti-tumour, hypoglycaemic, neuroprotective and immunoregulatory properties. The use of coniferyl alcohol and taxifolin as substrates to produce silybin and isosilybin under the action of enzyme catalysis is the commonly used biosynthetic pathway of silymarin, which provides support for a comprehensive analysis of the synthetic pathway of silymarin. In addition to medicinal use, the extracts of plants also have broad application prospects in the production of food, healthcare products, cosmetics and other aspects. In addition, the chemical composition, pharmacological mechanism and synthetic biology of S. marianum need to be further studied, which is very important for its clinical efficacy and resource development.
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Affiliation(s)
- Xiaozhuang Zhang
- College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Meiqi Liu
- College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Zhen Wang
- College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Panpan Wang
- College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Lingyang Kong
- College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Jianhao Wu
- College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Wei Wu
- College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Lengleng Ma
- College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Shan Jiang
- College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Weichao Ren
- College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Likun Du
- First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Wei Ma
- College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Xiubo Liu
- College of Jiamusi, Heilongjiang University of Chinese Medicine, Jiamusi, China
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Xie J, Ye Z, Xu X, Chang A, Yang Z, Wu Q, Pan Q, Wang Y, Chen Y, Ma X, Miao H. Microvesicles from quiescent and TGF-β1 stimulated hepatic stellate cells: Divergent impact on hepatic vascular injury. PLoS One 2024; 19:e0306775. [PMID: 38985836 PMCID: PMC11236151 DOI: 10.1371/journal.pone.0306775] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2024] [Accepted: 06/24/2024] [Indexed: 07/12/2024] Open
Abstract
BACKGROUND This study evaluated the effect of microvesicles(MVs) from quiescent and TGF-β1 stimulated hepatic stellate cells (HSC-MVs, TGF-β1HSC-MVs) on H2O2-induced human umbilical vein endothelial cells (HUVECs) injury and CCl4-induced rat hepatic vascular injury. METHODS HUVECs were exposed to hydrogen peroxide (H2O2) to establish a model for vascular endothelial cell injury. HSC-MVs or TGF-β1HSC-MVs were co-cultured with H2O2-treated HUVECs, respectively. Indicators including cell survival rate, apoptosis rate, oxidative stress, migration, invasion, and angiogenesis were measured. Simultaneously, the expression of proteins such as PI3K, AKT, MEK1+MEK2, ERK1+ERK2, VEGF, eNOS, and CXCR4 was assessed, along with activated caspase-3. SD rats were intraperitoneally injected with CCl4 twice a week for 10 weeks to induce liver injury models. HSC-MVs or TGF-β1HSC-MVs were injected into the tail vein of rats. Liver and hepatic vascular damage were also detected. RESULTS In H2O2-treated HUVECs, HSC-MVs increased cell viability, reduced cytotoxicity and apoptosis, improved oxidative stress, migration, and angiogenesis, and upregulated protein expression of PI3K, AKT, MEK1/2, ERK1/2, VEGF, eNOS, and CXCR4. Conversely, TGF-β1HSC-MVs exhibited opposite effects. CCl4- induced rat hepatic injury model, HSC-MVs reduced the release of ALT and AST, hepatic inflammation, fatty deformation, and liver fibrosis. HSC-MVs also downregulated the protein expression of CD31 and CD34. Conversely, TGF-β1HSC-MVs demonstrated opposite effects. CONCLUSION HSC-MVs demonstrated a protective effect on H2O2-treated HUVECs and CCl4-induced rat hepatic injury, while TGF-β1HSC-MVs had an aggravating effect. The effects of MVs involve PI3K/AKT/VEGF, CXCR4, and MEK/ERK/eNOS pathways.
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Affiliation(s)
- Jianlong Xie
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
- Department of Cardiothoracic Surgery Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Zhirong Ye
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Xiaobing Xu
- Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Anzhi Chang
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
- Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Ziyi Yang
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Qin Wu
- Department of Cardiothoracic Surgery Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Qunwen Pan
- Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Yan Wang
- Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Yanyu Chen
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
- Key Laboratory of Liver Injury Diagnosis and Repair, Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Xiaotang Ma
- Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Huilai Miao
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
- Key Laboratory of Liver Injury Diagnosis and Repair, Guangdong Medical University, Zhanjiang, Guangdong, China
- General Surgery, Liaobu Hospital, Dongguan, Guangdong, China
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Gharib OA, Fahmy HA, Abdou FY. Role of Olive Leaf Extract, Mesenchymal Stem Cells or Low Radiation Dose in Alleviating Hepatic Injury in Rats. Dose Response 2024; 22:15593258241289301. [PMID: 39483141 PMCID: PMC11526167 DOI: 10.1177/15593258241289301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Accepted: 08/28/2024] [Indexed: 11/03/2024] Open
Abstract
Objectives This study was conducted to determine the efficacy of mesenchymal stem cells (MSCs) or low-dose gamma radiation (LDR) on liver injury compared to the effect of olive leaf extract as a hepatoprotective agent. Methods Rats were allocated into six groups; group I served as the negative control. Group II received 5% dextran sodium sulfate (DSS) in its drinking water for 1 week. Group III was injected with a single dose of 1 × 106 bone marrow-derived mesenchymal stem cells (BM-MSCs) intravenously. Group IV was treated as in group III after 5% DSS treatment. Group V was given 5% DSS, followed by olive leaf extract (OLE) (1000 mg/ kg, oral). Group VI: 5% DSS for 1 week, then was exposed to low-dose gamma radiation (LDR) (0.05 Gy). Results Rats treated with OLE, BM-MSCs, or exposed to LDR exerted significant alleviation in all hepatic biomarkers, significant enhancements in oxidative stress parameters, and improvements in inflammatory biomarkers Interleukin-1 beta (IL-1β) and Interferon gamma (INF-γ) hepatic contents compared with those of the DSS group. Histological pictures emphasized the biochemical findings. Conclusions BM-MSCs might be a valuable therapeutic approach to overcome hepatic injury. Exposure to LDR provided protective mechanisms that allow the body to survive better.
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Affiliation(s)
- Ola A. Gharib
- Drug Radiation Research Department, National Center for Radiation Research and Technology, Egyptian Atomic Energy Authority (EAEA), Cairo, Egypt
| | - Hanan A. Fahmy
- Drug Radiation Research Department, National Center for Radiation Research and Technology, Egyptian Atomic Energy Authority (EAEA), Cairo, Egypt
| | - Fatma Y. Abdou
- Drug Radiation Research Department, National Center for Radiation Research and Technology, Egyptian Atomic Energy Authority (EAEA), Cairo, Egypt
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Zhao Y, Dai E, Dong L, Yuan J, Zhao Y, Wu T, Kong R, Li M, Wang S, Zhou L, Yang Y, Kong H, Zhao Y, Qu H. Available and novel plant-based carbon dots derived from Vaccaria Semen carbonisata alleviates liver fibrosis. Front Mol Biosci 2023; 10:1282929. [PMID: 38116381 PMCID: PMC10729316 DOI: 10.3389/fmolb.2023.1282929] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Accepted: 10/27/2023] [Indexed: 12/21/2023] Open
Abstract
Background: Liver fibrosis represents an intermediate stage in the progression of liver disease, and as of now, there exists no established clinical therapy for effective antifibrotic treatment. Purpose: Our aim is to explore the impact of Carbon dots derived from Vaccaria Semen Carbonisata (VSC-CDs) on carbon tetrachloride-induced liver fibrosis in mice. Methods: VSC-CDs were synthesized employing a modified pyrolysis process. Comprehensive characterization was performed utilizing various techniques, including transmission electron microscopy (TEM), multiple spectroscopies, X-ray photoelectron spectroscopy (XPS), and high-performance liquid chromatography (HPLC). A hepatic fibrosis model induced by carbon tetrachloride was utilized to evaluate the anti-hepatic fibrosis effects of VSC-CDs. Results: VSC-CDs, exhibiting a quantum yield (QY) of approximately 2.08%, were nearly spherical with diameters ranging from 1.0 to 5.5 nm. The VSC-CDs prepared in this study featured a negative charge and abundant chemical functional groups. Furthermore, these particles demonstrated outstanding dispersibility in the aqueous phase and high biocompatibility. Moreover, VSC-CDs not only enhanced liver function and alleviated liver damage in pathomorphology but also mitigated the extent of liver fibrosis. Additionally, this study marks the inaugural demonstration of the pronounced activity of VSC-CDs in inhibiting inflammatory reactions, reducing oxidative damage, and modulating the TGF-β/Smad signaling pathway. Conclusion: VSC-CDs exerted significant potential for application in nanodrugs aimed at treating liver fibrosis.
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Affiliation(s)
- Yafang Zhao
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Ertong Dai
- Qingdao Eighth People’s Hospital, Qingdao, Shandong, China
| | - Liyang Dong
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Jinye Yuan
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Yusheng Zhao
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Tong Wu
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Ruolan Kong
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Menghan Li
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Shuxian Wang
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Long Zhou
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Yingxin Yang
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Hui Kong
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Yan Zhao
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Huihua Qu
- Center of Scientific Experiment, Beijing University of Chinese Medicine, Beijing, China
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Tan J, Chen M, Liu M, Chen A, Huang M, Chen X, Tian X, Chen W. Exosomal miR-192-5p secreted by bone marrow mesenchymal stem cells inhibits hepatic stellate cell activation and targets PPP2R3A. J Histotechnol 2023; 46:158-169. [PMID: 37226801 DOI: 10.1080/01478885.2023.2215151] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Accepted: 05/12/2023] [Indexed: 05/26/2023]
Abstract
Bone marrow mesenchymal stem cell (BSMC)-derived extracellular vehicles (EVs) have a pivotal therapeutic potential in hepatic fibrosis (HF). Activation of hepatic stellate cells (HSCs) is the key mechanism in HF progression. Downregulation of miR-192-5p was previously observed in activated HSCs. Nonetheless, the functions of BSMC-derived exosomal miR-192-5p in activated HSCs remain unclear. In this study, transforming growth factor (TGF)-β1 was used to activate HSC-T6 cells to mimic HF in vitro. Characterization of BMSCs and BMSC-derived EVs was performed. Cell-counting kit-8 assay, flow cytometry, and western blotting revealed that TGF-β1 increased cell viability, promoted cell cycle progression, and induced upregulation of fibrosis markers in HSC-T6 cells. Overexpression of miR-192-5p or BMSC-derived exosomal miR-192-5p suppressed TGF-β1-triggered HSC-T6 cell activation. RT-qPCR revealed that protein phosphatase 2 regulatory subunit B'' alpha (PPP2R3A) was downregulated in miR-192-5p-overexpressed HSC-T6 cells. Luciferase reporter assay was used for verifying the relation between miR-192-5p and PPP2R3A, which showed that miR-192-5p targeted PPP2R3A in activated HSC-T6 cells. Collectively, BMSC-derived exosomal miR-192-5p targets PPP2R3A and inhibits activation of HSC-T6 cells.
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Affiliation(s)
- Jie Tan
- Department of Gastroenterology, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan, China
| | - Mingtao Chen
- Department of Gastroenterology, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan, China
| | - Meng Liu
- Department of Gastroenterology, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan, China
| | - Aifang Chen
- Department of Gastroenterology, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan, China
| | - Min Huang
- Department of Gastroenterology, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan, China
| | - Xiaoli Chen
- Department of Gastroenterology, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan, China
| | - Xia Tian
- Department of Gastroenterology, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan, China
| | - Wei Chen
- Department of Gastroenterology, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan, China
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Varjavand P, Hesampour A. The Role of Mesenchymal Stem Cells and Imatinib in the Process of Liver Fibrosis Healing Through CCL2-CCR2 and CX3CL1-CX3CR1 Axes. Rep Biochem Mol Biol 2023; 12:350-358. [PMID: 38317807 PMCID: PMC10838597 DOI: 10.61186/rbmb.12.2.350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Accepted: 11/09/2023] [Indexed: 02/07/2024]
Abstract
Background Persistent liver damage contributes to the development of liver fibrosis, marked by an accumulation of extracellular matrix. Macrophages play a pivotal role in this process, with the CCL2-CCR2 and CX3CR1-CX3CL1 axes serving as key regulators of macrophage recruitment, liver infiltration, and differentiation. In this study, utilizing a rat model of carbon tetrachloride (CCL4)-induced liver fibrosis, we aimed to investigate the impact of imatinib and bone marrow-derived mesenchymal stem cells (BM-MSCs) on the expression of these axis. Methods Sixteen Sprague-Dawley rats were divided into four groups: healthy, liver fibrosis, imatinib-recipient, and BM-MSC-recipient. Treatment effects were evaluated using histopathology and Sirus-red staining. Quantitative real-time PCR was employed to analyze changes in the expression of the genes CCL2, CCR2, CX3CL1, and CX3CR1. Results Histopathological assessments revealed the efficacy of imatinib and BM-MSCs in mitigating liver fibrosis. Our findings demonstrated a significant reduction in CCL2 and CCR2 expression in both imatinib and BM-MSCs treatment groups compared to the liver fibrosis group. Conversely, the gene expression of CX3CL1 and CX3CR1 increased in both therapeutic groups compared to the liver fibrosis groups. Conclusions The notable decrease in CCL2-CCR2 genes in both therapeutic groups suggests that BM-MSCs and imatinib may contribute to a decline in inflammatory macrophages within the liver. The lower CCL2-CCR2 expression in imatinib-recipient rats indicates better efficacy in modulating the recruitment of inflammatory macrophages. The elevated expression of CX3CL1 in BM-MSC-recipient rats suggests a greater impact on the polarization of LY6Chigh (inflammatory) to LY6Clow (anti-inflammatory) macrophages, warranting further investigation.
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Affiliation(s)
- Parisa Varjavand
- Department of Biology, Islamic Azad University Central Tehran Branch, Tehran, Iran.
| | - Ardeshir Hesampour
- Department of Biology, Islamic Azad University Central Tehran Branch, Tehran, Iran.
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Mobasher MA, Ahmed EI, Hakami NY, Germoush MO, Awad NS, Khodeer DM. The Combined Effect of Licorice Extract and Bone Marrow Mesenchymal Stem Cells on Cisplatin-Induced Hepatocellular Damage in Rats. Metabolites 2023; 13:metabo13010094. [PMID: 36677019 PMCID: PMC9861302 DOI: 10.3390/metabo13010094] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Revised: 12/12/2022] [Accepted: 12/20/2022] [Indexed: 01/11/2023] Open
Abstract
Drug-induced liver damage is a life-threatening disorder, and one major form of it is the hepatotoxicity induced by the drug cisplatin. In folk medicine, Licorice (Glycyrrhiza glabra (is used for detoxification and is believed to be a potent antioxidant. Currently, the magically self-renewable potential of bone marrow mesenchymal stem cells (BM-MSCs) has prompted us to explore their hepatoregenerative capability. The impact of G. glabra extract (GGE) and BM-MSCs alone and, in combination, on protecting against hepatotoxicity was tested on cisplatin-induced liver injury in rats. Hepatic damage, as revealed by liver histopathology and increased levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and malondialdehyde (MDA), was elevated in rats by received 7 mg/kg of cisplatin intraperitoneally. The combination of GGE and BM-MSCs returned the enzyme levels to near the normal range. It also improved levels of liver superoxide dismutase (SOD) and glutathione (GSH) and reduced MDA levels. Additionally, it was found that when GGE and BM-MSCs were used together, they significantly downregulated caspase9 (Casp9), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), and interleukin-1β (IL-1β), which are involved in severe proinflammatory and apoptotic signaling cascades in the liver. Moreover, combining GGE and BM-MSCs led to the normal result of hepatocytes in several examined liver histological sections. Therefore, our findings suggest that GGE may have protective effects against oxidative liver damage and the promising regenerative potential of BM-MSCs.
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Affiliation(s)
- Maysa A. Mobasher
- Department of Pathology, Biochemistry Division, College of Medicine, Jouf University, Sakaka 72388, Saudi Arabia
- Correspondence: (M.A.M.); (D.M.K.)
| | - Eman Ibrahim Ahmed
- Pharmacology and Therapeutics Department, College of Medicine, Jouf University, Sakaka 72346, Saudi Arabia
- Pharmacology Department, Faculty of Medicine, Fayoum University, Fayoum 63511, Egypt
| | - Nora Y. Hakami
- Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21423, Saudi Arabia
| | - Mousa O. Germoush
- Biology Department, College of Science, Jouf University, Sakaka 72388, Saudi Arabia
| | - Nabil S Awad
- Department of Genetics, Faculty of Agriculture and Natural Resources, Aswan University, Aswan 81528, Egypt
- College of Biotechnology, Misr University for Science and Technology, Giza 12563, Egypt
| | - Dina M. Khodeer
- Department of Pharmacology & Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt
- Correspondence: (M.A.M.); (D.M.K.)
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Off-the-shelf GMP-grade UC-MSCs as therapeutic drugs for the amelioration of CCl4-induced acute-on-chronic liver failure in NOD-SCID mice. Int Immunopharmacol 2022; 113:109408. [DOI: 10.1016/j.intimp.2022.109408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Revised: 10/16/2022] [Accepted: 10/28/2022] [Indexed: 11/10/2022]
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11
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Transplantation of adipose-derived mesenchymal stem cells ameliorates acute hepatic injury caused by nonsteroidal anti-inflammatory drug diclofenac sodium in female rats. Biomed Pharmacother 2022; 155:113805. [PMID: 36271578 DOI: 10.1016/j.biopha.2022.113805] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2022] [Revised: 09/30/2022] [Accepted: 10/02/2022] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND Although the beneficial role of adipose-derived mesenchymal stem cells (AD-MSCs) in acute liver injury has been addressed by numerous studies employing different liver injury inducers, the role of rat AD-MSCs (rAD-MSCs) in diclofenac sodium (DIC) - induced acute liver injury has not yet been clarified. OBJECTIVE This study aimed to investigate whether rat adipose- rAD-MSCs injected intraperitoneal could restore the DIC-induced hepatoxicity. METHODS Hepatotoxicity was induced by DIC in a dose-based manner, after which intraperitoneal injection of rAD-MSCs was performed. RESULTS Here, the transplanted cells migrated to the injured liver, and this was evidenced by detecting the specific SRY in the liver samples. After administering DIC, a significant decrease in body weight, survival rate, serum proteins, antioxidants, anti-apoptotic gene expression, and certain growth factors, whereas hepatic-specific markers, pro-inflammatory mediators, and oxidative, pro-apoptotic, and ER-stress markers were elevated. These adverse effects were significantly recovered after engraftment with rAD-MSCs. This was evidenced by enhanced survival and body weight, improved globulin and albumin values, increased expression of SOD, GPx, BCL-2, VEGF, and FGF-basic expression, and decreased serum ALT, AST, ALP, and total bilirubin. rAD-MSCs also reduced liver cell damage by suppressing the expression of MDA, IL-1B, IL-6, BAX, JNK, GRP78/BiP, CHOP, XBP-1, and cleaved caspase 3/7. Degenerative hepatic changes and multifocal areas of fatty change within liver cells were observed in DIC-received groups. These changes were improved with the transplantation of rAD-MSCs. CONCLUSIONS We could conclude that targeted AD-MSCs could be applied to reduce hepatic toxicity caused by NSAIDs (DIC).
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12
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Hassan HM, Li J. Prospect of Animal Models for Acute-on-chronic Liver Failure: A Mini-review. J Clin Transl Hepatol 2022; 10:995-1003. [PMID: 36304511 PMCID: PMC9547251 DOI: 10.14218/jcth.2022.00086] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Revised: 03/31/2022] [Accepted: 04/10/2022] [Indexed: 12/04/2022] Open
Abstract
Acute-on-chronic liver failure (ACLF) is a clinical syndrome that develops in patients with chronic liver diseases following a precipitating event and associated with a high mortality rate due to systemic multiorgan failure. Establishing a suitable and stable animal model to precisely elucidate the molecular basis of ACLF pathogenesis is essential for the development of effective early diagnostic and treatment strategies. In this context, this article provides a concise and inclusive review of breakthroughs in ACLF animal model development.
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Affiliation(s)
- Hozeifa Mohamed Hassan
- Precision Medicine Center, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Jun Li
- Precision Medicine Center, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Correspondence to: Jun Li, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, Zhejiang 310003. China. ORCID: https://orcid.org/0000-0002-7236-8088. Tel/Fax: +86-571-87236425, E-mail:
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13
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Kattner AA. Greek gods and the double-edged sword of liver regeneration. Biomed J 2021; 44:515-520. [PMID: 34715410 PMCID: PMC8640535 DOI: 10.1016/j.bj.2021.10.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Accepted: 10/19/2021] [Indexed: 02/07/2023] Open
Abstract
In the current issue of the Biomedical Journal we gain an insight into the regeneration of liver tissue and how an over-the-counter supplement, stem cells and two plant extracts counteract liver damage. Furthermore the advances against hepatitis C virus are presented, the role of long non-coding RNA elucidated as well as the potential of an adhesion G protein-coupled receptor. In another contribution, the definition and evolutionary impact of copy number variants is clarified. Also, the polymorphism of a scaffolding caspase is investigated. We furthermore learn about the relation between SARS-CoV2 mutants in dependence of geography and explore the challenges of telemedicine in a complex healthcare field. A novel approach to engineering artificial grafts is presented, the challenges of total knee arthroplasty discussed as well as a possible mean of sinus floor elevation for dental implants. At last the concept of flipped classroom is scrutinized in terms of usefulness for a hospital in Taiwan.
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14
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Hu S, Lian PP, Hu Y, Zhu XY, Jiang SW, Ma Q, Li LY, Yang JF, Yang L, Guo HY, Zhou H, Yang CC, Meng XM, Li J, Li HW, Xu T, Zhou H. The Role of IL-35 in the Pathophysiological Processes of Liver Disease. Front Pharmacol 2021; 11:569575. [PMID: 33584256 PMCID: PMC7873894 DOI: 10.3389/fphar.2020.569575] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Accepted: 12/10/2020] [Indexed: 12/23/2022] Open
Abstract
It is known that liver diseases have several characteristics of massive lipid accumulation and lipid metabolic disorder, and are divided into liver inflammation, liver fibrosis, liver cirrhosis (LC), and hepatocellular carcinoma (HCC) in patients. Interleukin (IL)-35, a new-discovered cytokine, can protect the liver from the environmental attack by increasing the ratio of Tregs (T regulatory cells) which can increase the anti-inflammatory cytokines and inhibit the proliferation of immune cellular. Interestingly, two opposite mechanisms (pro-inflammatory and anti-inflammatory) have connection with the ultimate formation of liver diseases, which suggest that IL-35 may play crucial function in the process of liver diseases through immunosuppressive regulation. Besides, some obvious advantages also imply that IL-35 can be considered as a new therapeutic target to control the progression of liver diseases, while its mechanism of function still needs further research.
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Affiliation(s)
- Shuang Hu
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, China.,Institute for Liver Diseases of Anhui Medical University, Hefei, China
| | - Pan-Pan Lian
- School of Pharmacy, NanJing University, NanJing, China
| | - Ying Hu
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, China.,Institute for Liver Diseases of Anhui Medical University, Hefei, China
| | - Xing-Yu Zhu
- National Drug Clinical Trial Institution, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Shao-Wei Jiang
- The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Qiang Ma
- Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Liang-Yun Li
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, China.,Institute for Liver Diseases of Anhui Medical University, Hefei, China
| | - Jun-Fa Yang
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, China.,Institute for Liver Diseases of Anhui Medical University, Hefei, China
| | - Li Yang
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, China.,Institute for Liver Diseases of Anhui Medical University, Hefei, China
| | - Hai-Yue Guo
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, China.,Institute for Liver Diseases of Anhui Medical University, Hefei, China
| | - Hong Zhou
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, China.,Institute for Liver Diseases of Anhui Medical University, Hefei, China
| | - Chen-Chen Yang
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, China.,Institute for Liver Diseases of Anhui Medical University, Hefei, China
| | - Xiao-Ming Meng
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, China.,Institute for Liver Diseases of Anhui Medical University, Hefei, China
| | - Jun Li
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, China.,Institute for Liver Diseases of Anhui Medical University, Hefei, China
| | - Hai-Wen Li
- The Third Affiliated Hospital of Anhui Medical University, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Tao Xu
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, China.,Institute for Liver Diseases of Anhui Medical University, Hefei, China
| | - Huan Zhou
- National Drug Clinical Trial Institution, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
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Al-Dhamin Z, Liu LD, Li DD, Zhang SY, Dong SM, Nan YM. Therapeutic efficiency of bone marrow-derived mesenchymal stem cells for liver fibrosis: A systematic review of in vivo studies. World J Gastroenterol 2020; 26:7444-7469. [PMID: 33384547 PMCID: PMC7754546 DOI: 10.3748/wjg.v26.i47.7444] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Revised: 10/31/2020] [Accepted: 11/12/2020] [Indexed: 02/06/2023] Open
Abstract
Although multiple drugs are accessible for recovering liver function in patients, none are considered efficient. Liver transplantation is the mainstay therapy for end-stage liver fibrosis. However, the worldwide shortage of healthy liver donors, organ rejection, complex surgery, and high costs are prompting researchers to develop novel approaches to deal with the overwhelming liver fibrosis cases. Mesenchymal stem cell (MSC) therapy is an emerging alternative method for treating patients with liver fibrosis. However, many aspects of this therapy remain unclear, such as the efficiency compared to conventional treatment, the ideal MSC sources, and the most effective way to use it. Because bone marrow (BM) is the largest source for MSCs, this paper used a systematic review approach to study the therapeutic efficiency of MSCs against liver fibrosis and related factors. We systematically searched multiple published articles to identify studies involving liver fibrosis and BM-MSC-based therapy. Analyzing the selected studies showed that compared with conventional treatment BM-MSC therapy may be more efficient for liver fibrosis in some cases. In contrast, the cotreatment presented a more efficient way. Nevertheless, BM-MSCs are lacking as a therapy for liver fibrosis; thus, this paper also reviews factors that affect BM-MSC efficiency, such as the implementation routes and strategies employed to enhance the potential in alleviating liver fibrosis. Ultimately, our review summarizes the recent advances in the BM-MSC therapy for liver fibrosis. It is grounded in recent developments underlying the efficiency of BM-MSCs as therapy, focusing on the preclinical in vivo experiments, and comparing to other treatments or sources and the strategies used to enhance its potential while mentioning the research gaps.
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Affiliation(s)
- Zaid Al-Dhamin
- Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University & Hebei Key Laboratory of Mechanism of Liver Fibrosis in Chronic Liver Disease, Shijiazhuang 050051, Hebei Province, China
| | - Ling-Di Liu
- Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University & Hebei Key Laboratory of Mechanism of Liver Fibrosis in Chronic Liver Disease, Shijiazhuang 050051, Hebei Province, China
| | - Dong-Dong Li
- Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University & Hebei Key Laboratory of Mechanism of Liver Fibrosis in Chronic Liver Disease, Shijiazhuang 050051, Hebei Province, China
| | - Si-Yu Zhang
- Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University & Hebei Key Laboratory of Mechanism of Liver Fibrosis in Chronic Liver Disease, Shijiazhuang 050051, Hebei Province, China
| | - Shi-Ming Dong
- Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University & Hebei Key Laboratory of Mechanism of Liver Fibrosis in Chronic Liver Disease, Shijiazhuang 050051, Hebei Province, China
| | - Yue-Min Nan
- Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University & Hebei Key Laboratory of Mechanism of Liver Fibrosis in Chronic Liver Disease, Shijiazhuang 050051, Hebei Province, China
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16
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Zhang D, Song D, Shi L, Sun X, Zheng Y, Zeng Y, Wang X. Mechanisms of interactions between lung-origin telocytes and mesenchymal stem cells to treat experimental acute lung injury. Clin Transl Med 2020; 10:e231. [PMID: 33377639 PMCID: PMC7724099 DOI: 10.1002/ctm2.231] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Revised: 10/31/2020] [Accepted: 11/03/2020] [Indexed: 12/13/2022] Open
Abstract
Acute lung injury is a serious form and major cause of patient death and still needs efficient therapies. The present study evidenced that co-transplantation of mesenchymal stem cells (MSCs) and telocytes (TCs) improved the severity of experimental lung tissue inflammation, edema, and injury, where TCs increased MSCs migration into the lung and the capacity of MSCs proliferation and movement. Of molecular mechanisms, Osteopontin-dominant networks were active in MSCs and TCs, and might play supportive and nutrimental roles in the interaction between MSCs and TCs, especially activated TCs by lipopolysaccharide. The interaction between epidermal growth factor and its receptor from MSCs and TCs could play critical roles in communications between MSCs and TCs, responsible for MSCs proliferation and movement, especially after inflammatory activation. Our studies provide the evidence that TCs possess nutrimental and supportive roles in implanted MSCs, and co-transplantation of MSCs and TCs can be a new alternative in the therapy of acute lung injury.
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Affiliation(s)
- Ding Zhang
- Zhongshan Hospital Institute of Clinical ScienceZhongshan HospitalShanghai Medical CollegeFudan UniversityShanghaiChina
- Department of Pulmonary and Critical Care MedicineHuashan HospitalFudan UniversityShanghaiChina
| | - Dongli Song
- Zhongshan Hospital Institute of Clinical ScienceZhongshan HospitalShanghai Medical CollegeFudan UniversityShanghaiChina
| | - Lin Shi
- Zhongshan Hospital Institute of Clinical ScienceZhongshan HospitalShanghai Medical CollegeFudan UniversityShanghaiChina
| | - Xiaoru Sun
- Zhongshan Hospital Institute of Clinical ScienceZhongshan HospitalShanghai Medical CollegeFudan UniversityShanghaiChina
| | - Yonghua Zheng
- Department of Respiratory MedicineShanghai Jinshan Tinglin HospitalShanghaiChina
| | - Yiming Zeng
- Department of Pulmonary and Critical Care MedicineClinical Center for Molecular Diagnosis and TherapyThe Second Affiliated Hospital of Fujian Medical UniversityQuanzhouFujian ProvinceChina
| | - Xiangdong Wang
- Zhongshan Hospital Institute of Clinical ScienceZhongshan HospitalShanghai Medical CollegeFudan UniversityShanghaiChina
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