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Abstract: SA-PO351

The Effects of Regulatory T Cell Induction by Mesenchymal Stem Cells Pretreated with Interferon-Gamma on Renal Inflammation and Fibrosis

Session Information

Category: Development, Stem Cells, and Regenerative Medicine

  • 600 Development, Stem Cells, and Regenerative Medicine

Authors

  • Kurawaki, So, Hiroshima Daigaku Byoin, Hiroshima, Hiroshima, Japan
  • Nakashima, Ayumu, Yamanashi Daigaku Igakubu Fuzoku Byoin, Chuo, Yamanashi, Japan
  • Ishiuchi, Naoki, Hiroshima Daigaku Byoin, Hiroshima, Hiroshima, Japan
  • Kanai, Ryo, Hiroshima Daigaku Byoin, Hiroshima, Hiroshima, Japan
  • Sasaki, Kensuke, Hiroshima Daigaku Byoin, Hiroshima, Hiroshima, Japan
  • Masaki, Takao, Hiroshima Daigaku Byoin, Hiroshima, Hiroshima, Japan
Background

Mesenchymal stem cells (MSCs) exert the anti-inflammatory effect by secreting various humoral factors, which contribute to the regeneration of damaged tissues. Interferon-gamma (IFN-γ) can enhance the anti-inflammatory effect of MSCs, and the enhancement of regulatory T (Treg) cell induction is thought to be an underlying mechanism. In this study, we investigated the effects of Treg cell induction by IFN-γ MSCs on renal inflammation and fibrosis.

Methods

Rats were subjected to contralateral nephrectomy and unilateral renal ischemia reperfusion injury (IRI) by clamping the renal artery. Subsequently, phosphate-buffered saline, untreated MSCs (control MSCs), or IFN-γ MSCs were administered to the renal artery. At 7 or 21 days after administration, rats were sacrificed and their kidneys were collected to examine renal inflammation and fibrosis. In addition, in vitro experiments were performed to examine expression levels of indoleamine 2,3-dioxygenase (IDO), the key regulator of Treg cell induction, in IFN-γ MSCs. Finally, we examined the therapeutic effects of IFN-γ MSCs transfected with IDO1 siRNA in IRI rats.

Results

Administration of IFN-γ MSCs induced Treg cells and inhibited infiltration of inflammatory cells in IRI rats more drastically than control MSCs. In addition, administration of IFN-γ MSCs more significantly attenuated renal fibrosis compared with administration of control MSCs. IDO expression levels in conditioned medium from MSCs were enhanced by pretreatment with IFN-γ. Functional experiments demonstrated that IDO1 knockdown in IFN-γ MSCs reduced their anti-inflammatory and anti-fibrotic effects in IRI rats by reducing Treg cell induction.

Conclusion

Our findings suggest that the increase of Treg cells induced by enhanced secretion of IDO by IFN-γ MSCs played a pivotal role in their anti-fibrotic effects. Administration of IFN-γ MSCs may potentially be a useful therapy to prevent renal fibrosis progression.