Mesenchymal stem cells attenuate peritoneal injury through secretion of TSG-6
Nan Wang1, Qinggang Li, Li Zhang
1State Key Laboratory of Kidney Diseases, Department of Nephrology, PLA General Hospital and Military Medical Postgraduate College, Beijing, China.
Background:
Mesothelial cell injury plays an important role in peritoneal fibrosis. Present clinical therapies aimed at alleviating peritoneal fibrosis have been largely inadequate. Mesenchymal stem cells (MSCs) are efficient for repairing injuries and reducing fibrosis. This study was designed to investigate the effects of MSCs on injured mesothelial cells and peritoneal fibrosis.
Methodology/Principal Findings:
Rat bone marrow-derived MSCs (5 × 10(6)) were injected into Sprague-Dawley (SD) rats via tail vein 24 h after peritoneal scraping. Distinct reductions in adhesion formation; infiltration of neutrophils, macrophage cells; number of fibroblasts; and level of transforming growth factor (TGF)-β1 were found in MSCs-treated rats. The proliferation and repair of peritoneal mesothelial cells in MSCs-treated rats were stimulated. Mechanically injured mesothelial cells co-cultured with MSCs in transwells showed distinct increases in migration and proliferation. In vivo imaging showed that MSCs injected intravenously mainly accumulated in the lungs which persisted for at least seven days. No apparent MSCs were observed in the injured peritoneum even when MSCs were injected intraperitoneally. The injection of serum-starved MSCs-conditioned medium (CM) intravenously reduced adhesions similar to MSCs. Antibody based protein array of MSCs-CM showed that the releasing of TNFα-stimulating gene (TSG)-6 increased most dramatically. Promotion of mesothelial cell repair and reduction of peritoneal adhesion were produced by the administration of recombinant mouse (rm) TSG-6, and were weakened by TSG-6-RNA interfering.
Conclusions/Significance:
Collectively, these results indicate that MSCs may attenuate peritoneal injury by repairing mesothelial cells, reducing inflammation and fibrosis. Rather than the engraftment, the secretion of TSG-6 by MSCs makes a major contribution to the therapeutic benefits of MSCs.
Insights
Mesenchymal stem cells (MSCs) reduce peritoneal fibrosis by repairing mesothelial cells and decreasing inflammation. The therapeutic effect is primarily due to the secretion of TNFα-stimulating gene (TSG)-6, not cell engraftment.
Area of Science:
- Regenerative Medicine
- Stem Cell Biology
- Fibrosis Research
Background:
- Mesothelial cell injury is a key factor in peritoneal fibrosis.
- Current treatments for peritoneal fibrosis are insufficient.
- Mesenchymal stem cells (MSCs) show potential for tissue repair and anti-fibrotic effects.
Purpose of the Study:
- To investigate the therapeutic effects of MSCs on injured mesothelial cells.
- To evaluate the impact of MSCs on peritoneal fibrosis in a rat model.
Main Methods:
- Mesenchymal stem cells (MSCs) were administered to rats with peritoneal injury.
- Mesothelial cell function was assessed in vitro and in vivo.
- The role of MSC-secreted factors, particularly TNFα-stimulating gene (TSG)-6, was investigated.
Main Results:
- MSC treatment significantly reduced peritoneal adhesions, inflammation, and fibrosis.
- MSCs promoted the proliferation and repair of injured mesothelial cells.
- The conditioned medium from MSCs, especially TSG-6, mimicked the therapeutic effects of MSCs.
Conclusions:
- MSCs attenuate peritoneal injury and fibrosis through mesothelial cell repair and reduced inflammation.
- The therapeutic benefits of MSCs are mainly attributed to secreted factors like TSG-6, rather than cell engraftment.
