Abstract: SA-PO698
Comparison of Mesenchymal Stem Cells (MSCs) and Extracellular Vesicles (EVs) in the Treatment of Experimental Peritoneal Fibrosis
Session Information
- Peritoneal Dialysis - II
November 04, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Dialysis
- 608 Peritoneal Dialysis
Authors
- Gouveia, Priscila Q, University of São Paulo, São Paulo, Brazil
- Silva, Cleonice, University of São Paulo, São Paulo, Brazil
- Noronha, Irene L., University of São Paulo, São Paulo, Brazil
Background
Long-term peritoneal dialysis is associated with the development of structural and functional changes in the peritoneal membrane, leading to fibrosis and ultrafiltration failure. Infusion of MSCs represents a potential strategy to treat fibrotic processes, due to paracrine effects. EVs released by MSCs are responsible for cell-cell interactions and possibly for the therapeutic effects of MSCs on tissue regeneration. Our aim was to compare the effects of MSCs with EV in an experimental model of peritoneal fibrosis (PF).
Methods
PF was induced in male Wistar rats by intraperitoneal (IP) injections of 0.1% chlorhexidine gluconate (CG), on alternate days for 30 days. MSCs obtained from adipose tissue were isolated and characterized by flow cytometry and in vitro differentiation. EVs obtained from MSCs supernatants were isolated by differential ultracentrifugation and characterized by Bradford assay, Zetasizer Nano and scanning electron microscopy. MSCs or EVs were administrated IP on days 3 and 10 after PF induction. The study groups consisted of: Control (n=6), normal rats receiving only vehicle (saline); PF (n=9), rats receiving CG injections to develop PF; PF+MSC (n=7), PF rats treated with 2x106 MSCs and PF+EV (n=7), PF rats treated with 30µg EVs.
Results
Administration of MSCs or EVs prevented peritoneal thickening and ameliorated ultrafiltration. Both treatments significantly decreased the expression of genes associated with fibrosis (TGF-β,FSP-1 and SMAD3). In addition, both treatments reduced the inflammatory infiltrate and the expression of TNF-α and VEGF.
Conclusion
We conclude that MSCs and EVs are equally efficient in blocking the PF process in this experimental model of PF.
| Control | PF | PF+MSC | PF+VE | |
| Peritoneal Thickness(μm) | 26±0 | 64±14* | 23±2# | 26±6# |
| Ultrafiltration(mL) | 13±1 | 3±1* | 5±1*# | 6±1*#§ |
| TGF-β(mRNA) | 1±1 | 12±1* | 3±1# | 1±0# |
| FSP-1(mRNA) | 1±1 | 18±1* | 1±0# | 1±0# |
| Smad-3(mRNA) | 1±0 | 8±1* | 1±0# | 1±1# |
| Macrophages(cells/mm2) | 106±35 | 404±122* | 263±49*# | 147±17# |
| T-cells(cell/mm2) | 4±1 | 87±31* | 7±3# | 11±4# |
| VEGF(mRNA) | 1±1 | 21±2* | 4±3# | 2±1# |
| TNF-α(mRNA) | 1±1 | 14±1* | 1±1# | 1±1# |
*p<0.05vsControl;#p<0.05vsPF;§<0.05vsFP+MSC
Funding
- Government Support - Non-U.S.