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Abstract: SA-OR038

Therapeutic Efficacy and Safety of Human Adipose-Derived Stem Cells for Anti-GBM Nephritis

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Shimamura, Yuko, Nagoya University Graduate School of Medicine, Nagoya, Japan
  • Tsuboi, Naotake, Nagoya University Graduate School of Medicine, Nagoya, Japan
  • Kamimura, Yutaka, Nagoya University Graduate School of Medicine, Nagoya, Japan
  • Maruyama, Shoichi, Nagoya University Graduate School of Medicine, Nagoya, Japan
Background

Mesenchymal stem cells (MSCs), which exert immunomodulatory function, would be one of the promising therapeutic agents for inflammatory disorders. We have been intensively studied adipose derived stem cells (ASCs) cultured under low serum conditions (LASCs) and recently demonstrated that systemic administration of syngeneic LASCs ameliorated anti-GBM nephritis in rats more effectively than ACSs grown under high serum conditions (HASCs). In the current study, we investigated therapeutic potency of human LASCs for rat anti-GBM nephritis.

Methods

Anti-GBM nephritis was induced by intravenous injection of TF78, a monoclonal anti-glomerular basement membrane antibody, to female WKY/NCrj rats. 2×106 human LASCs, HASCs or bone marrow derived MSCs (BMMSCs) were administrated to them on day 0, 2, 4 and sacrificed on day 7. Therapeutic efficacy was evaluated by proteinuria during observation period and serum creatinine (sCr), BUN, histological renal damage on day 7. Distribution of administrated MSCs was observed by In Vivo Imaging System. The clotting time after addition of MSCs into plasma was measured. The expression of tissue factor on the MSC surface was analyzed by flow cytometry.

Results

ASC-treatment demonstrated significant amelioration in TF78-induced renal dysfunction. Histologically, crescent formation and
accumulations of CD68+ or CD163+ macrophages in inflamed glomeruli were significantly decreased in ASC-treated groups compared with the BMMSC-treated group. Although the therapeutic efficacy of HASC slightly surpassed that of LASC, therapy-related animal death caused by pulmonary accumulations of administrated-ASCs occurred in 4 out of 12 HASC-treated rats, while none in LASC-treated animals. Procoagulant function, which has emerged as a critical aspect in clinical application of ASCs, was remarkably diminished in LASCs compared with HASCs as evidenced with similar clotting time and tissue factor expression to BMMSCs.

Conclusion

Human ASCs have therapeutic potential for anti-GBM nephritis as well as syngeneic ASCs compared with BMMSCs. Although HASCs shows slightly superior efficacy, it has a serious safety drawback compared with LASCs. From a comprehensive perspective, LASCs would be advantageous in therapeutic potential for clinical use.