Effect of Adipose Tissue-Derived Mesenchymal Stem Cells in a Rat Model of Chronic Renal Allograft Rejection.

R. Pepineli, F. Silva, P. Gouveia, G. Tavora, S. Gomes, I. Noronha.

Renal Division, University of Sao Paulo, Sao Paulo, Brazil.

Meeting: 2016 American Transplant Congress

Abstract number: 481

Keywords: Kidney, Rat, Stem cells

Session Information

Session Name: Concurrent Session: Bone Marrow Transplantation and Chimerism: Animal Models

Session Type: Concurrent Session

Date: Tuesday, June 14, 2016

Session Time: 4:30pm-6:00pm

Presentation Time: 5:42pm-5:54pm

Location: Room 313

Adipose tissue-derived mesenchymal stem cells (ASC) may represent a new strategy to prevent allograft rejection after kidney transplantation due to its immunomodulatory properties. In the present study, the effect of ASC on the chronic renal allograft rejection model was analyzed.

The chronic rejection model was developed by performing orthotopic kidney transplantation using Fisher rats (F344) as donors and Lewis rats (LEW) as recipients, without immunosuppression. ASC were isolated from Lewis rats and expanded until the 4^th passage. Rats that underwent transplantation were divided into 3 groups (n=6/group) and followed up for 6 months: Syngeneic (SYNG), untreated LEW rats receiving kidney from LEW rats; Allogeneic (ALLO), LEW rats receiving allogeneic kidney from F344; and ALLO+ASC, ALLO rats treated with ASC (3 doses of 1×10⁶, at 0, 1 and 3 months after transplantation). Blood pressure, urinary protein excretion, creatinine clearance, renal histology, immunohistochemistry for macrophages and T-cells, and qPCR for inflammatory cytokines were analyzed. Results are presented as mean±SEM; *p<0.05 vs SYNG, #p<0.05 vs ALLO.

At 6 months, the ALLO group presented significantly increased levels of blood pressure and urinary protein excretion and decreased creatinine clearance. Treatment with ASC ameliorated all these parameters. ALLO animals developed significantly interstitial fibrosis compared with the SYNG group, reversed by ASC treatment. In addition, ASC also provided amelioration of allograft inflammation, characterized by decreased inflammatory cells and cytokine expression.

SYNG
ALLO

ALLO+ASC

Blood Pressure (mmHg) 145±2 166±1^* 147±2^#

Urinary Protein Excretion (mg/24h) 79±17 167±29^* 119±8^#

Creatinine Clearance (ml/min) 1.2±0.1 0.6±0.4^* 1.5±0.3^#

Interstitial Fibrosis (%) 7.2±0.6 24.4±2.3^* 17.2±0.6^*#

MÃ˜ (cells/mm²) 8±2 31±4^* 4±0^#

T-cells (cells/mm²) 8±3 26±3^* 10±2^#

INF-Î³ 1.0±0.1 2.1±0.2^* 0.4±0.3^#

TNF-Î± 1.0±0.1 2.0±0.4^* 1.0±0.4^#

IL-1ÃŸ 1.0±0.2 2.1±0.3^* 1.0±0.3^#

IL-6 1.0±0.2 5.4±0.3^* 3.0±0.4^*^#

In the chronic allograft rejection model Fisher to Lewis, administration of ASC was effective in protecting kidney allograft function, interstitial fibrosis and tissue inflammation. These findings may have important implications in the clinical settings and need further investigation.

CITATION INFORMATION: Pepineli R, Silva F, Gouveia P, Tavora G, Gomes S, Noronha I. Effect of Adipose Tissue-Derived Mesenchymal Stem Cells in a Rat Model of Chronic Renal Allograft Rejection. Am J Transplant. 2016;16 (suppl 3).

To cite this abstract in AMA style:

Pepineli R, Silva F, Gouveia P, Tavora G, Gomes S, Noronha I. Effect of Adipose Tissue-Derived Mesenchymal Stem Cells in a Rat Model of Chronic Renal Allograft Rejection. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/effect-of-adipose-tissue-derived-mesenchymal-stem-cells-in-a-rat-model-of-chronic-renal-allograft-rejection/. Accessed November 21, 2024.

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