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Abstract: SA-PO433

Mesenchymal Stem Cells Cultured in IFN-γ-Containing Medium Ameliorate Experimental Renal Fibrosis

Session Information

Category: Development, Stem Cells, and Regenerative Medicine

  • 500 Development, Stem Cells, and Regenerative Medicine

Authors

  • Kanai, Ryo, Hiroshima University Hospital, Hiroshima, Japan
  • Nakashima, Ayumu, Hiroshima University, Hiroshima, Japan
  • Doi, Shigehiro, Hiroshima University Hospital, Hiroshima, Japan
  • Ishiuchi, Naoki, Hiroshima University Hospital, Hiroshima, Japan
  • Doi, Toshiki, Hiroshima University Hospital, Hiroshima, Japan
  • Masaki, Takao, Hiroshima University Hospital, Hiroshima, Japan
Background

Mesenchymal stem cells (MSCs) have been reported to promote regeneration of damaged tissues and suppress fibrosis. Recently, interferon-γ (IFN-γ) was reported to enhance the paracrine activities of MSCs. In this study, we investigated the effect of MSCs cultured in IFN-γ-containing medium on inflammation and fibrosis using unilateral ureter obstruction (UUO) and ischemia-reperfusion injury (IRI) models.

Methods

At 4 days after the UUO operation, we injected rat MSCs (3×106 cells/rat) cultured in 10% FBS-containing DMEM (rMSCs) or IFN-γ-containing medium (IFN-γ rMSCs), or PBS only (Control) through the rat tail vein. In addition, we injected rats after an IRI operation through the abdominal aorta with PBS, rMSCs, or IFN-γ rMSCs (5×105 cells/rat). Next, we investigated the effect of IFN-γ human MSC (hMSC)-conditioned medium (CM) on TGF-β1-induced fibrotic changes by western blotting. As an anti-inflammatory mediator, we analyzed CM from IFN-γ hMSCs by an enzyme-linked immunosorbent assay.

Results

Immunohistochemical staining revealed that IFN-γ-rMSCs strongly ameliorated interstitial fibrosis. IFN-γ rMSCs also attenuated renal fibrosis and inflammation more significantly than rMSCs in IRI models. IFN-γ hMSCs-CM decreased the expression of phosphorylated Smad2 and αSMA compared with hMSCs-CM without IFN-γ stimulation. We found that prostaglandin E2 (PGE2) expression was significantly increased in IFN-γ hMSCs-CM. Knockdown of prostaglandin E synthase (PTGES), which is a synthetic enzyme of PGE2, weakened the anti-fibrotic effect of IFN-γ MSCs in IRI models.

Conclusion

Our findings indicate that IFN-γ potentiates the anti-fibrosis and anti-inflammatory abilities of MSCs and administration of MSCs cultured in IFN-γ-containing medium has the potential to be a useful therapy to prevent the progression of renal fibrosis.