Abstract: TH-PO323

TLR3 Activation Enhances the Renoprotective Effect of Low Serum Cultured Adipose Derived Stromal Cell for Anti-GBM Nephritis

Session Information

Category: Acute Kidney Injury

  • 002 AKI: Repair and Regeneration

Authors

  • Kamimura, Yutaka, Nagoya University Graduate School of Medicine, Nagoya, AICHI-KEN, Japan
  • Tsuboi, Naotake, Nagoya University Graduate School of Medicine, Nagoya, AICHI-KEN, Japan
  • Kitagawa, Akimitsu, Nagoya University Graduate School of Medicine, Nagoya, AICHI-KEN, Japan
  • Katsuno, Takayuki, Nagoya University Graduate School of Medicine, Nagoya, AICHI-KEN, Japan
  • Maruyama, Shoichi, Nagoya University Graduate School of Medicine, Nagoya, AICHI-KEN, Japan
Background

We established human adipose tissue-derived stromal cells (hASC) cultured in low (2%) serum (LASC), which demonstrated great therapeutic potential for inflammatory diseases. We have already reported that LASC significantly attenuated rat anti-GBM glomerulonephritis than did hASCs cultured in high (20%) serum (HASC) by promoting the phenotypic conversion of macrophages to immunoregulatory cells. However, the mechanism for LASC to exert greater anti-inflammatory function than HASC was partly evaluated. Based on our DNA microarray data in hASCs, we identified TLR3 as a candidate gene that underlies LASC-mediated immuneregulation. In the current study, we investigated the effect of TLR3 activation of ASC in vitro and in vivo.

Methods

Human abdominal subcutaneous adipose tissue was obtained from patients underwent liposuction or gynecological surgery. Cells were cultured under the two conditions; a low serum culture medium containing 2% fetal bovine serum (FBS) and a high serum culture medium containing 20% FBS. ELISA for HGF, IL-6 and MCP-1 were performed on hASC supernatant cultured with or without poly(I:C) for TLR3 ligand or LPS for TLR4 ligand. Anti-GBM model rats were administered 1×106 hASC primed by poly(I:C) or not on days 0, 2 and 4 via the tail vain and we evaluated BUN, sCr, proteinuria and histologic assessment of glomerular crescent formation on day 7.

Results

LASC secreted more HGF, IL-6 and MCP-1 in response to poly(I:C) than HASC, but not to LPS, and these growth factor and cytokines were increased in a dose dependent manner of poly(I:C). In rat anti-GBM model, significant disease amelioration was verified in less elevation of BUN and sCr, and was further evidenced in significant reduction of glomerular crescent formation in animals treated with TLR3-activated LASCs compared to others.

Conclusion

Our data suggest that LASC can be characterized by immune response through TLR3 activation, and that poly(I:C) priming may enhance LASC-mediated renoprotective effects for anti-GBM nephritis.