Abstract: SA-PO441
Spleen Is the Key Organ for the Renoprotective Potential of Adipose-Derived Mesenchymal Stromal Cells
Session Information
- Development and Regenerative Medicine
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Development, Stem Cells, and Regenerative Medicine
- 500 Development, Stem Cells, and Regenerative Medicine
Authors
- Shimamura, Yuko, Nagoya University Graduate School of Medicine, Nagoya, Japan
- Furuhashi, Kazuhiro, Nagoya University, Nagoya, Japan
- Tsuboi, Naotake, Fujita Health University School of Medicine, Toyoake, AICHI-KEN, Japan
- Maruyama, Shoichi, Nagoya University Graduate School of Medicine, Nagoya, Japan
Background
Administration of mesenchymal stromal cells (MSCs), which exert immunomodulatory function, is considerable therapeutic agents for inflammatory disorders. However, it remains unknown where MSCs are distributed and act after administration. In this study, we evaluated the therapeutic efficacy of human adipose derived stromal cells (ASCs) on anti-GBM nephritis rats and where they exert therapeutic effects.
Methods
Anti-GBM nephritis was induced by monoclonal anti-glomerular basement membrane antibody, to female WKY/NCrj rats. We administrated human ASCs or bone marrow derived MSCs (BMMSCs) to them intravenously on day 0, 2, 4 and sacrificed on day 7. Therapeutic efficacy was evaluated by serum Cre, BUN, histological renal damage on day 7. To track MSCs, we also administrated MSCs labeled with DiD to the diseased rats and observed their distribution by flow cytometry and fluorescence microscope. Next, we inhibited MSCs accumulation in organs to reveal where they act.
Results
Human ASC-treatment decreased serum Cre and BUN in anti GBM antibody-induced renal dysfunction compared with BMMSCs. Histologically, crescent formation and accumulations of total macrophages in inflamed glomeruli were significantly decreased in ASC-treated groups. DiD positive cells are observed in lungs, kidneys, spleens and livers. The therapeutic efficacy was preserved even after reduction of ASCs accumulation in lungs. Interestingly, splenectomy counteracted the effectiveness of ASCs completely, while sham operation did not affect their therapeutic effects.
Conclusion
Human ASCs have therapeutic potential for anti-GBM nephritis compared with BMMSCs. Spleen is a key organ for the therapeutic effect of MSCs. The elucidation of this mechanism would lead to the efficacy and safety of MSC based therapy.