ArticleImmunologic research2015
Mesenchymal stromal cell-dependent reprogramming of Kupffer cells is mediated by TNF-α and PGE2 and is crucial for liver transplant tolerance.
Article in Immunologic research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 25 citations in OpenAlex.
- Mesenchymal stem cells: a potential therapeutic strategy for IgA nephropathy.Frontiers in pharmacology · 2026Review
- Mesenchymal stem cell therapy for liver transplantation: clinical progress and immunomodulatory properties.Stem cell research & therapy · 2024Review
- Effect of the Combination of Everolimus and Mesenchymal Stromal Cells on Regulatory T Cells Levels and in a Liver Transplant Rejection Model in Rats.Frontiers in immunology · 2022Article
- Advances in mesenchymal stem cell therapy for immune and inflammatory diseases: Use of cell-free products and human pluripotent stem cell-derived mesenchymal stem cells.Stem cells translational medicine · 2021Review
- Mesenchymal Stromal Cell Therapy in Novel Porcine Model of Diffuse Liver Damage Induced by Repeated Biliary Obstruction.International journal of molecular sciences · 2021Article
- Role of prostaglandin E2 in tissue repair and regeneration.Theranostics · 2021Review
- Applications of Mesenchymal Stem Cells in Liver Fibrosis: Novel Strategies, Mechanisms, and Clinical Practice.Stem cells international · 2021Review
- Mesenchymal Stromal Cell Therapy in Solid Organ Transplantation.Frontiers in immunology · 2020Review
- Mesenchymal stromal cells promote liver regeneration through regulation of immune cells.International journal of biological sciences · 2020Review
- Research Status of Mesenchymal Stem Cells in Liver Transplantation.Cell transplantation · 2019Review
- MiRNA-22 inhibits oncogene galectin-1 in hepatocellular carcinoma.Oncotarget · 2016Article
- Tetrandrine identified in a small molecule screen to activate mesenchymal stem cells for enhanced immunomodulation.Scientific reports · 2016Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The role of mesenchymal stromal cells (MSCs) in the modulation of liver transplant tolerance has attracted significant interest. However, the interaction between MSCs and Kupffer cells (KCs) has received little attention, and the effect of this interaction on liver transplant tolerance remains unclear. KCs were cultured in the presence and absence of MSCs. After 24 h, cells were treated with lipopolysaccharide (LPS), after which the production of cytokines and the expression of surface antigens were measured for cell function identification. Moreover, the effects of the KCs and the prostaglandin E2 (PGE2) levels produced by the MSCs were determined using an experimental rat liver transplantation model. Blood and liver samples were collected at three time points after transplantation for further analysis. After LPS treatment, when compared with the KC single cultures, the expression of pro-inflammatory cytokines (IL-1β, IL-6, MHC-II, CD40, CD80, and CD86) in the coculture system was down-regulated, whereas the expression of anti-inflammatory cytokines (TGF-β, IL-4, PGE2, and IL-10) was markedly increased. These data indicate that MSCs can reprogram the phenotype of KCs. However, KCs treated with miR/TNF-α (tumor necrosis factor) plasmid prior to coculture to inhibit the production of TNF-α resulted in an inhibition of the reprogramming effect of MSCs. Moreover, overexpression of PGE2 in MSCs increased the effect of MSCs on KC reprogramming. After rat liver transplantation, allograft recipients that received MSCs showed better allograft tolerance when compared with rats in which KC function was inhibited. Furthermore, rats treated with MSCs overexpressing PGE2 demonstrated the best liver tolerance of all of the groups tested. MSCs reprogram the phenotype of KCs through TNF-α and PGE2, and this process is crucial for the immunomodulatory function of MSCs in liver transplantation.
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