Abstract: FR-PO257
Amniotic Fluid-Derived Mesenchymal Stem Cells (AFSCs) Are Renoprotective in Established Experimental CKD
Session Information
- Stem Cells
November 03, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Developmental Biology and Inherited Kidney Diseases
- 402 Stem Cells
Authors
- Cavaglieri, Rita de Cassia, University of São Paulo, São Paulo, SP, Brazil
- Prado, Thalita, University of São Paulo, São Paulo, SP, Brazil
- Albuquerque, Luísa, University of São Paulo, São Paulo, SP, Brazil
- Zugaib, Marcelo, University of São Paulo, São Paulo, SP, Brazil
- Bydlowski, Sergio P., University of São Paulo, São Paulo, SP, Brazil
- Noronha, Irene L., University of São Paulo, São Paulo, SP, Brazil
Background
AFSCs are a class of stem cells that present characteristics intermediate between embryonic stem cells (ESC) and adult mesenchymal stem cells (MSC). Given that the amniotic fluid consists of fetal urine, stem cell populations present in the amniotic fluid are likely derived from the fetal kidney. These characteristics have aroused great interest in the potential protective effects of AFSCs in renal diseases. The aim of this study was to analyze the effects of AFSCs in an experimental model of CKD, the 5/6 nephrectomy (Nx) model , after the disease has been established, in order to more closely resemble the clinical settings in humans.
Methods
Human AFSCs were isolated from second trimester amniocentesis samples by plastic adhesion and characterized as MSC. Male Wistar rats (n= 38) underwent 5/6 Nx or were Sham-operated. After 15 days, 14 rats were euthanized and renal disease was confirmed (Nx-15d). In subsequent experiments, the remaining 31 rats received 5x105 AFSCs or saline, injected under the kidney capsule, and were followed for an additional 15 days. These rats were divided into 4 groups: Sham 30d, Sham+AFSC 30d, sham rats receiving AFSCs; Nx, 5/6 nephrectomy; and Nx+AFSC, Nx rats receiving AFSCs. The table shows the parameters analyzed.
Results
Nx rats with established CKD and treated with AFSCs displayed significant reductions in blood pressure, albuminuria and glomerulosclerosis. In addition, they showed lower expression of α-SMA and ED-1, as well as higher expression of WT-1, in comparison with untreated Nx rats.
Conclusion
These results demonstrate that inoculation of AFSCs ameliorate renal disease in established chronic kidney disease.
| EXPERIMENTS AFTER ESTABLISHED CKD | ||||||
| 15 DAYS | 30 DAYS | |||||
| Sham 15d (n=7) | Nx 15d (n=7) | Sham 30d (n=6) | Sham+AFSC 30d (n=6) | Nx 30d (n=10) | Nx+AFSC30d (n=9) | |
| BP (mmHg) | 131±2 | 159±3* | 126±2 | 133±3a | 188±2a,b | 169±7a,b,c |
| uAlb (mg/24h) | 2±1 | 27±8* | 1±0 | 1±0 | 110±13a,b | 43±9c |
| Glomerulosclerosis (%) | 1.5±1 | 10.3±3 | 0.3±1 | 0.0±1 | 29.2±7a,b | 3.5±1c |
| Interstitial Fibrosis (%) | 2±0.3 | 6±0.5* | 4±1.1 | 3±0.4 | 11±0.4a,b | 11±0.6a,b |
| WT1 (cells/glom) | 11±1 | 7±0* | 11±1 | 11±0 | 6±0a,b,d | 9±1 |
| α-SMA (%) | 0.7±0.2 | 3.2±0.6* | 0.1±0.0 | 0.2±0.1 | 5.3±0.8a,b | 1.3±0.4c |
| ED1+ (cells/mm2) | 18±4 | 38±11 | 15±1 | 7±2 | 59±13a,b | 16±4c |
Mean±SEM: *p<0.05 vs Sham 15d; ap<0.01 vs Sham 30d; bp<0.001 vs Sham+AFSC 30d; cp<0.01 vs Nx 30d
Funding
- Government Support - Non-U.S.