Kidney Week

Abstract: SA-PO091

Tonsil-Derived Mesenchymal Stem Cells Protect the Kidney from Nephrotoxin-Induced AKI by an Amelioration of Oxidative Stress via Incorporation into Damaged Renal Tubules

Session Information

• AKI: Mechanisms - Primary Injury and Repair - II
  November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 103 AKI: Mechanisms

Authors

• Kang, Duk-Hee, Ewha University College of Medicine, Seoul, Korea (the Republic of)

Duk-Hee Kang,

• Ryu, Eun sun, Ewha University College of Medicine, Seoul, Korea (the Republic of)

Eun sun Ryu,

• Jung, Sung min, Ewha University College of Medicine, Seoul, Korea (the Republic of)

Sung min Jung,

• Kim, Dal-ah, Ewha University College of Medicine, Seoul, Korea (the Republic of)

Dal-ah Kim,

Background

The therapeutic effect of mesenchymal stem cells (MSCs) in repairing damaged renal cells in AKI has been demonstrated. Tonsil-derived MSCs (T-MSCs) derived from tonsillar tissues are reported to be effective in acute liver injury. The aim of this study is to investigate the therapeutic potential of T-MSCs in gentamicin-induced AKI

Methods

Twenty male Sprague-Dawley rats were divided into four groups: Control, GM (140 mg/kg/day, intraperitoneal injection for 10 days for 10 days), GM+T-MSCs (1x10⁷ cells, intravenous injection at 1 day after the 1st GM injection), and T-MSC group. To examine the intra-renal localization of T-MSCs, T-MSCs were labeled with PKH-26 red fluorescence before infusion. Measurement of BUN, Cr, proteinuria and histologic analysis including TUNEL staining were performed on 16 days of GM injection. Effect of T-MSC on renal tubular cells was also evaluated using a transwell co-culture system of NRK cells and T-MSC. Intracellular ROS was analyzed by measuring NOX activity, H₂O₂ generation, NOX mRNA expressions with DCF-DA staining

Results

The infusion of T-MSCs in animal model of GM-induced AKI preserved renal function with a decrease in proteinuria. T-MSCs also ameliorated renal tubular dilatation and reduced apoptosis of renal tubular cells, which was associated with decreased number of apoptotic cells, down-regulating apoptotic genes and up-regulating anti-apoptotic gene. In addition, T-MSCs resulted in suppression of oxidative stress as reflected by a decrease in the level of urinary 8-OHdG with an increase in antioxidant enzymes (GPx and catalase) in the renal tissue. PKH-26-labeled T-MSCs were identified within the renal cortex and localized primarily in the renal tubules. The in-vitro study revealed that T-MSC and/or T-MSC-conditioned media ameliorated GM-induced NOX-1 expression, H₂O₂ generation, and apoptosis of NRK cells.

Conclusion

Our study demonstrated that T-MSCs ameliorated GM-induced AKI by directly incorporating into the damaged renal tubules, exerting anti-apoptotic and anti-oxidative effects