Kidney Week

Abstract: SA-PO352

Tonsil-Derived Mesenchymal Stem Cells Alleviate Gentamicin (GM)-Induced AKI by an Amelioration of Oxidative Stress and Apoptosis via an Incorporation into Damaged Renal Tubules

Session Information

• Development, Organoids, Vascularized Kidneys, Nephrons, and More
  November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Development, Stem Cells, and Regenerative Medicine

• 600 Development, Stem Cells, and Regenerative Medicine

Authors

• Kang, Duk-Hee, Division of Nephrology, Ewha Womans University School of Medicine, Seoul, Korea (the Republic of)

Duk-Hee Kang,

• Yu, Mina, Division of Nephrology, Ewha Womans University School of Medicine, Seoul, Korea (the Republic of)

Mina Yu,

• Kim, Dal-Ah, Division of Nephrology, Ewha Womans University School of Medicine, Seoul, Korea (the Republic of)

Dal-Ah Kim,

• Jo, Chor ho, Hanyang Biomedical Research Institute, Hanyang University College of Medicine, Seoul, Korea (the Republic of)

Chor ho Jo,

Background

The therapeutic effect of mesenchymal stem cells (MSCs) in repairing damaged renal cells in AKI has been demonstrated. Human palatine tonsil is an attractive alternative high-yield source of adult stem cells since they are readily available from surgically removed waste tissue. The aim of this study is to investigate the therapeutic potential of T-MSCs in GM-induced AKI.

Methods

Twenty male Sprague-Dawley rats were divided into four groups: Control, GM (140 mg/kg/day, intraperitoneal injection 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 GM-induced AKI rats preserved renal function with a decrease in proteinuria. T-MSCs injection decreased apoptotic cells and the expression of Bax, cytochrome C, and cleaved caspase and increased Bcl-2. T-MSCs suppressed oxidative stress as reflected by a decrease in the level of urinary 8-OHdG with an increase in antioxidant enzymes (glutathione peroxidase and catalase) in the kidneys. Anti-human nuclei and PHK-26 staining demonstrated the localization of T-MSCs in the tubules of renal cortex. In-vitro study revealed that T-MSC 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.

Funding

• Government Support – Non-U.S.