Mesenchymal Stem Cells Attenuate Peritoneal Injury through Secretion of TSG-6

Abstract

BackgroundMesothelial 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 FindingsRat bone marrow-derived MSCs (5 ×106) 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/SignificanceCollectively, 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.

Cell-Derived Polymer/Extracellular Matrix Composite Scaffolds for Cartilage Regeneration, Part 1: Investigation of Cocultures and Seeding Densities for Improved Extracellular Matrix Deposition

“…One possible reason that the four chondrocyte containing constructs exhibited better cellular infiltration and distribution of matrices than the MSC generated constructs is that chondrocytes are smaller than MSCs; 10-15 mm in diameter compared to 20-30 mm. [55][56][57] Thus, it is probable that the chondrocytes penetrated the scaffold through the interconnected pores more readily than the MSCs, which remained primarily trapped at the surface of the scaffold.…”

Adenovirus-Mediated Over-Expression of Nrf2 Within Mesenchymal Stem Cells (MSCs) Protected Rats Against Acute Kidney Injury

“…5,6 According to numerous studies, MSCs exert their repairing effects on kidney via two important mechanisms including repopulation and paracrine actions. [6][7][8] The pathogenesis of AKI is complex, however, it has been shown that ischemia/reperfusion triggers AKI, mainly via aggravating stresses, inflammation and activation of renin-angiotensin system (RAS). 9 Hypoxia, serum deprivation and oxidative stress are important factors in the pathogenesis of AKI.…”

Adipose-derived mesenchymal stem cells transplantation facilitate experimental peritoneal fibrosis repair by suppressing epithelial–mesenchymal transition

“…Since MSCs possess many characteristics, including a multi-lineage potential [7], immunomodulatory properties [8], and self-renewal capability in vitro [9], they have been found to decrease fibrosis in the heart [10], lungs [11] and kidneys [12]. Moreover, injected bone marrow-derived MSCs (BMSCs) have been shown to differentiate into peritoneal mesothelial cells [13] and repair PF morphologically and functionally in animal models through anti-inflammatory and anti-EMT effects [14][15][16].…”