Abstract: SA-PO439
Systematic Implantation of Dedifferentiated Fat Cells (DFAT) Ameliorated the Monoclonal Antibody 1-22-3-Induced Glomerulonephritis with Stimulation of TSG-6
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
Author
- Maruyama, Takashi, Nihon University School of Medicine, Tokyo, Japan
Background
Implantation of mesenchymal stem cells has recently been reported to repair tissue injuries
through anti-inflammatory and immunosuppressive effects. We established dedifferentiated fat cells that
show identical characteristics to MSCs.
Methods
We examined the effects of 106 of DFAT cells infused through renal artery or tail vein on monoclonal
antibody 1-22-3-induced glomerulonephritis and adriamycin-induced nephropathy in rats. The mAb 1-22-3-injected rats were also implanted with 106 of DFAT cells transfected with TSG-6 siRNA through tail vein.
Results
Although DFAT cells transfused into blood circulation through the tail vein were trapped mainly in lungs
without reaching the kidneys, implantation of DFAT cells reduced proteinuria and improved glomerulosclerosis and
interstitial fibrosis. Implantation of DFAT cells through the tail vein significantly decreased expression of kidney injury
molecule-1, collagen IV and fibronectin mRNAs, whereas nephrin mRNA expression was increased. Implantation of
DFAT cells did not improve adriamycin-induced nephropathy, but significantly decreased the glomerular influx of
macrophages, common leukocytes and pan T cells. However, the glomerular influx of helper T cells, was increased.
Implantation of DFAT cells decreased expression of interleukin-6 and IL-12β mRNAs and increased expression of
TNF-stimulated gene-6 mRNA in renal cortex from mAb 1-22-3-injected rats. The basal level of TSG-6 protein was
significantly higher in DFAT cells than in fibroblasts. Expression of TSG-6 mRNA in MCs cocultured with DFAT cells
was significantly higher than in mesangial cells or DFAT cells alone. Systematic implantation of DFAT cells with
TSG-6 siRNA through tail vein did not improve proteinuria, renal dysfunction and renal degeneration in the mAb
1-22-3-injected rats.
Conclusion
Systematic implantation of DFAT cells effectively ameliorated mAb 1-22-3-induced glomerulonephritis
through immunosuppressive effects accompanied by the suppression of macrophage infiltration and expression of
IL-6, IL-10 and IL-12β, and increased production of serum and renal TSG-6 that improved the mAb 1-22-3-induced renal
degeneration by the immunosuppressive effects of TSG-6. Thus DFAT cells will be suitable cell source for the treatment
of immunological progressive renal diseases.