Abstract: FR-PO256

Mesenchymal Stem Cells Cultured in Serum-Free Medium Ameliorate Experimental Renal Fibrosis by Their Strong Immunosuppressive Effects

Session Information

  • Stem Cells
    November 03, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Developmental Biology and Inherited Kidney Diseases

  • 402 Stem Cells

Authors

  • Yoshida, Ken, Hiroshima University Hospital, Hiroshima, Japan
  • Nakashima, Ayumu, Hiroshima University Hospital, Hiroshima, Japan
  • Doi, Shigehiro, Hiroshima University Hospital, Hiroshima, Japan
  • Ueno, Toshinori, Hiroshima University Hospital, Hiroshima, Japan
  • Kato, Yukio, Graduate School of Biomedical & Sciences, Hiroshima University, Hiroshima, Japan
  • Higashi, Yukihito, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan
  • Masaki, Takao, Hiroshima University Hospital, Hiroshima, Japan
Background

The mechanism underlying the anti-inflammatory effect of mesenchymal stem cells (MSCs) has been elucidated. However, the anti-inflammatory effect of MSCs cultured in serum-free medium has not been clarified. Here we examined the effects of MSCs cultured in serum-free medium on infiltration of inflammatory cells and interstitial fibrosis induced by unilateral ureteral obstruction (UUO) operation in rats.

Results

At 4 days post-UUO operation, we injected rat MSCs cultured in 10% fetal bovine serum containing DMEM (10%MSCs) or serum-free medium (SF-MSCs) or PBS only (control) through the tail vein. Although retention of MSCs collected from green fluorescent protein-positive rats was only observed for 3 days with no difference between 10%MSCs and SF-MSCs, immunohistochemistry revealed that SF-MSCs strongly ameliorated infiltration of macrophages and interstitial fibrosis. Next we examined whether serum-free culture conditions enhanced the anti-fibrotic and immunosuppressive effects by paracrine manners. Incubation of cultured human kidney-2 cells in human MSC-conditioned medium suppressed transforming growth factor-β1-induced phosphorylation of Smad2 and α-smooth muscle actin, but there was no significant difference in culture from 10%MSCs and SF-MSCs. Co-cultures of human MSCs and human monocytic THP-1 cell-derived pro-inflammatory phenotype (M1) macrophages using a transwell system showed significant increases in cells positive for CD163 and CD206, immunomodulatory phenotype (M2) macrophage markers, in SF-MSCs compared with 10%MSCs.

Conclusion

These results show that transplantation of MSCs cultured in serum-free medium ameliorated infiltration of inflammatory cells and renal fibrosis in UUO rats compared with MSCs cultured in serum containing medium, in part by enhancement of M2 macrophage polarization from MSCs cultured in serum-free medium. The replacement of serum containing medium of MSCs to serum-free medium is thought to reduce the risk of infections, and transplantation of MSCs cultured in serum-free medium may help alleviate renal diseases in which inflammation plays a critical role.