Dataset Information

IL-1? Pretreatment Improves the Efficacy of Mesenchymal Stem Cells on Acute Liver Failure by Enhancing CXCR4 Expression.

ABSTRACT: Background:Mesenchymal stem cells (MSCs), with the powerful metabolic and functional supporting abilities for inflammatory diseases, may be an effective therapeutic strategy for acute liver failure (ALF). However, the efficacy of MSCs can still be promoted if pretreatment is applied to enhance their poor migration towards the damaged liver. The purpose of this study is to determine the effect of IL-1? pretreatment on the efficacy and homing ability of MSCs in ALF. Methods:MSCs were isolated by the whole bone marrow adherence method and characterized. The efficacy and homing ability of IL-1?-pretreated MSCs (Pre-MSCs) were examined in a rat ALF model and compared with that of MSCs and normal saline. Then, Western blot was performed to detect the c-Met and CXCR4 expression of MSCs and Pre-MSCs and followed by flow cytometry to detect the meaningful indicators. Finally, the migration abilities of different cells and different conditions were tested by the Transwell migration assay. Results:MSCs of ideal purity were successfully isolated and cultured. Comparing with MSCs, Pre-MSCs had significantly better efficacy on improving the survival rate and liver function of ALF rats. Further analyses of damaged liver tissues showed that IL-1? pretreatment significantly enhanced the efficacy of MSCs on suppressing liver necrosis. Besides, Pre-MSCs exhibited better effects in inhibiting apoptosis and activating proliferation. The results of tracing experiments with CM-Dil-labeled cells confirmed that more cells migrated to the damaged liver in the Pre-MSC group. In terms of mechanism, the CXCR4 expression was significantly enhanced by IL-1? pretreatment, and an increased migration ability towards SDF-1 that could be reversed by AMD3100 was found in Pre-MSCs. Conclusion:IL-1? pretreatment could enhance the homing ability of MSCs at least partially by increasing the expression of CXCR4 and further improve the efficacy of MSCs on ALF.

SUBMITTER: Nie H

PROVIDER: S-EPMC7364198 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

IL-1<i>β</i> Pretreatment Improves the Efficacy of Mesenchymal Stem Cells on Acute Liver Failure by Enhancing CXCR4 Expression.

Nie He H An Fangmei F Mei Jie J Yang Cheng C Zhan Qiang Q Zhang Qinglin Q

Stem cells international 20200707

<h4>Background</h4>Mesenchymal stem cells (MSCs), with the powerful metabolic and functional supporting abilities for inflammatory diseases, may be an effective therapeutic strategy for acute liver failure (ALF). However, the efficacy of MSCs can still be promoted if pretreatment is applied to enhance their poor migration towards the damaged liver. The purpose of this study is to determine the effect of IL-1<i>β</i> pretreatment on the efficacy and homing ability of MSCs in ALF.<h4>Methods</h4>M ...[more]

PMID: 32724311

Similar Datasets

Project description:The wound healing process initiates after injury to a tissue and involves a series of orchestrated events to minimize the invasion of foreign matters such as bacteria and efficiently regenerate the damaged tissue. A variety of cells must be recruited to the tissue during wound healing. However, this process is severely disrupted in patients suffering from chronic illness, including diabetes, leading to impaired healing or non-healing wounds. Current avenues of treatment include negative-pressure therapy, wound debridement, growth factor replacement, and cell-based therapies. Among these therapies, mesenchymal stem cells (MSCs) delivery to the wound holds a very high promise due to the innate abilities of MSCs that include immunogenicity, plasticity, and self-renewal. Bone marrow derived MSCs have been shown to promote more rapid wound healing by increased cytokine production in diabetic mice. However, the lack of understanding of the mechanical and chemical interaction of the transplanted MSCs with the factors present in the regenerative niches limits their efficacy in the wound bed. In this study, we sought to understand how the changes in MSC biochemical and biophysical properties can affect their function in vitro and in vivo. We demonstrate that pretreatment of MSCs with the mechano-stimulatory soluble factor transforming growth factor (TGF-β1), which is highly expressed in injury sites, improves wound closure in a syngeneic murine wound model. This improved wound closure correlated with increased invasion into the wound bed. In vitro studies demonstrated that TGF-β1 pretreatment expedited wound closure by increasing adhesion, traction force, and migration even after removal of the stimulus. Furthermore, this response was mediated by the cytoskeletal protein focal adhesion kinase. Taken together, this study suggests that defined chemical stimuli can benefit site specific adaptability of MSCs to improve their function and therapeutic usefulness.

Project description:BackgroundAlthough it has been preclinically suggested that adipose tissue-derived mesenchymal stem cell (ADSC)-based therapy could effectively treat chronic liver diseases, the hepatic engraftment of ADSCs is still extremely low, which severely limits their long-term efficacy for chronic liver diseases. This study was designed to investigate the impact of antioxidant preconditioning on hepatic engraftment efficiency and therapeutic outcomes of ADSC transplantation in liver fibrotic mice.MethodsLiver fibrosis model was established by using intraperitoneal injection of carbon tetrachloride (CCl4) in the male C57BL/6 mice. Subsequently, the ADSCs with or without antioxidant pretreatment (including melatonin and reduced glutathione (GSH)) were administrated into fibrotic mice via tail vein injection. Afterwards, the ADSC transplantation efficiency was analyzed by ex vivo imaging, and the liver functions were assessed by biochemical analysis and histopathological examination, respectively. Additionally, a typical hydrogen peroxide (H2O2)-induced cell injury model was applied to mimic the cell oxidative injury to further investigate the protective effects of antioxidant preconditioning on cell migration, proliferation, and apoptosis of ADSCs.ResultsOur data showed that antioxidant preconditioning could enhance the therapeutic effects of ADSCs on liver function recovery by reducing the level of AST, ALT, and TBIL, as well as the content of hepatic hydroxyproline and fibrotic area in liver tissues. Particularly, we also found that antioxidant preconditioning could enhance hepatic engraftment efficiency of ADSCs in liver fibrosis model through inhibiting oxidative injury.ConclusionsAntioxidant preconditioning could effectively improve therapeutic effects of ADSC transplantation for liver fibrosis through enhancing intrahepatic engraftment efficiency by reducing oxidative injuries. These findings might provide a practical strategy for enhancing ADSC transplantation and therapeutic efficiency.

Dataset Information

IL-1? Pretreatment Improves the Efficacy of Mesenchymal Stem Cells on Acute Liver Failure by Enhancing CXCR4 Expression.

Publications

IL-1<i>β</i> Pretreatment Improves the Efficacy of Mesenchymal Stem Cells on Acute Liver Failure by Enhancing CXCR4 Expression.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets