Abstract: SA-PO442
Cell Sheet Therapy to Suppress Renal Vascular Injury and Fibrosis in Rat Unilateral Ureteral Obstruction and Ischemia-Reperfusion Injury Models
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
- Oka, Masatoshi, University of Utah, Salt Lake City, Utah, United States
- Imafuku, Aya, Tokyo Women''s Medical University, Shinjuku-ku, Tokyo, Japan
- Nitta, Kosaku, Tokyo Women's Medical University, Shinjuku-ku, TOKYO, Japan
- Okano, Teruo, Tokyo Women''s Medical University, Shinjuku-ku, Tokyo, Japan
Background
CKD is a growing and unsolved problem and a new strategy to suppress renal fibrosis is required. In CKD, lack of vasoprotective factors such as VEGF and HGF causes renal vascular injury and subsequent progressive fibrosis. Recently, many researchers reported that administration of vasoprotective factors or the cells producing those factors suppressed vascular injury and fibrosis in preclinical studies. However, the therapeutic effects were limited due to their short half-life in circulation or low retention of the transplanted cells in the kidneys. To solve this problem, we applied cell sheet technology for kidney diseases. We aimed to suppress renal vascular injury and fibrosis by long-term and direct supply of vasoprotective factors secreted form cell sheets.
Methods
Using a temperature responsive culture dish, HGF transgenic mesothelial cell sheet (HGF-tg MC sheet) and rat bone marrow derived mesenchymal stromal cell sheets (MSC sheet) were prepared. In rat UUO or IRI models, the renal capsule was removed and cell sheets were transplanted onto the kidney surface. We analyzed the behavior of the transplanted cells (immunostaining, in vivo imaging system), morphology of the kidney/renal microvascular density/ renal artery blood flow rate (US, CT), and renal fibrosis. The effects were compared between those in receiving intravenous administration of rHGF protein or MSCs.
Results
Transplantation of HGF-tg MC sheets significantly protected microvascular density, maintained renal artery blood flow, and suppressed renal fibrosis compared with intravenous administration of rHGF protein. Transplantation of MSC sheets showed superior survival of the donor cells in the kidney compared with intravenous administration of MSCs, resulted in strong suppression of renal fibrosis and protection of microvascular density in the whole kidney.
Conclusion
Transplantation of cell sheets onto the kidney surface ameliorated renal vascular injury and suppressed renal fibrosis in UUO and IRI by long-term and direct supply of vasoprotective factors secreted from grafted cells. Renal treatment with cell sheets would be a promising strategy.
Funding
- Commercial Support – CellSeed, Inc.