Abstract: SA-PO429
Engineered Bone Marrow Stem Cell-Sheets Alleviate Renal Fibrosis in a Chronic Glomerulonephritic Rat Model
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
- Huang, Yufeng, University of Utah, Salt Lake City, Utah, United States
Background
Although mesenchymal stem cell (MSC)-based regenerative therapy is currently being developed for treatment of kidney diseases, it is ineffective due to a few functional cells present at the target tissue. Thus, we developed an MSC-engineered cell sheet technology using the temperature-responsive cell culture surfaces to release cultured MSCs as confluent living cell-sheets. We hypothesized that this new technology would improve MSC transplantation efficiency and therapeutically reduce kidney disease.
Methods
. Three experimental groups included normal, untreated disease control but received sham surgery, and allogeneic bone marrow-derived MSC-sheets treated diseased rats. The chronic glomerulonephritis was induced by two injections of anti-Thy 1.1 antibody (OX-7) in rats. The MSC-sheets were prepared and transplanted as patches onto the surface of the two kidneys of each rat in the treated group at 24h after the first injection of OX-7.
Results
At 4 weeks, retention of the transplanted MSC-sheets was confirmed and animals with MSC-sheets showed significant reductions in proteinuria, glomerular staining for periodic acid-Schiff positive materials, collagen III and fibronectin, and in renal TGFß1, PAI-1, collagen I and fibronectin mRNA and protein levels. Treatment also altered renal overexpression of KIM-1 and NGAL mRNAs and reversed disease induced reduction of WT-1, podocin and nephrin mRNAs. Furthermore, treatment enhanced regenerative gene expression, and IL-10, Bcl-2, and HO-1 mRNA levels but reduced TSP-1 levels, NF-kB and NAPDH oxidase production in the kidney, which were consistent with the reduction of glomerular macrophage cell infiltration and glomerular and tubular cell apoptosis.
Conclusion
These observations strongly support our hypothesis that MSC-sheets facilitated MSC transplantation and effectively retarded progressive renal fibrosis through paracrine or autocrine signaling involved cellular inflammation, oxidative stress, apoptosis and regeneration.