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Abstract: PO0405

Subcutaneous Adipose Stromal Cell-Derived Secretome Improves Renal Function and Inflammation in Established AKI

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Ullah, Md Mahbub, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Collett, Jason Andrieu, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Traktuev, Dmitry, University of Florida, Gainesville, Florida, United States
  • Coleman, Michael E., Theratome Bio, Inc, Indianapolis, IN, Indiana, United States
  • Basile, David P., Indiana University School of Medicine, Indianapolis, Indiana, United States
Background

Previous studies demonstrated that human adipose derived stromal cells (ASC) attenuated the development of acute kidney injury (AKI) and preserved vascular density, when administered in the suprarenal aorta immediately following ischemia reperfusion (IRI). Recently, stem cell derived secretome, has received attention for the potential treatment of renal disease. We hypothesized that cell-free, concentrated fraction of ASC-derived secretome would improve renal function in a well-established rat model of AKI.

Methods

Male Sprague Dawley rats underwent bilateral IRI-40 min to induce AKI. 24 hours later, renal function was evaluated (serum creatinine; SCre) and rats were randomized into vehicle or secretome-treated groups. Rats received subcutaneous (SQ) injection either secretome (2 mg/kg in 1 ml) or saline (1 ml) on day 1 and day 3 post IRI. After 5 days of IRI, kidneys were collected for further analysis.

Results

At 24 h post IRI, SCre levels were 3.3±0.2 mg/dl in vehicle treated rats and 3.1±0.1 mg/dl in secretome treated rats (P=0.31). SCre level significantly (P=0.03) decreased in secretome treated ratscompared to the vehicle treated rats across 5 days study period. After 24 h administration of first secretome injection, there was a significant reduction of SCre level (27.8%, P>0.001) in secretome treated rats compared to their baseline. There was a significant increase of infiltration of dendritic/macrophage cells following IRI which was significantly reduced in secretome group (IRI; 1.2 X106 vs. secretome; 5.0 X105 cells/g kidney; p<0.05). Additionally, there was a significant reduction of TH-17 cells (CD4+IL-17+) following secretome treatment compared to vehicle group (secretome: 2.0 X104 vs. IRI: 4.6 X104 cells/g kidney; p<0.05). Kidney tissue stained with periodic acid-Schiff reagent shown secretome treatment improved the degree of tubular damage following IRI.

Conclusion

These data indicate that SQ injection of secretome following established AKI hastens recovery of renal function and reduces infiltration of renal inflammatory cells. Thus, secretome might represent a useful option to treat AKI.

Funding

  • NIDDK Support