Kidney Week

Abstract: TH-PO0577

Protective Effect of Tonsil-Derived Mesenchymal Stem Cells on Peritoneal Fibrosis by Inhibiting Oxidative Stress

Session Information

• Development, Stem Cells, and Regenerative Medicine
  November 06, 2025 | Location: Exhibit Hall, 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, Department of Internal Medicine of Ewha Womans University, Seoul, Korea (the Republic of)

Duk-Hee Kang, MD, PhD

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

Dal-Ah Kim, PhD

• Jo, Chor ho, Division of Nephrology, Department of Internal Medicine of Ewha Womans University, Seoul, Korea (the Republic of)

Chor ho Jo, PhD

• Lee, Yoonseo, Division of Nephrology, Department of Internal Medicine of Ewha Womans University, Seoul, Korea (the Republic of)

Yoonseo Lee

• Im, Huigyeong, Division of Nephrology, Department of Internal Medicine of Ewha Womans University, Seoul, Korea (the Republic of)

Huigyeong Im

Background

Mesenchymal stem cells (MSCs) have regenerative capability and exert paracrine actions on damaged tissues and have recently received a new attention due to its preventive effect on organ fibrosis by inhibiting epithelial-to-mesenchymal transition (EMT). The EMT of mesothelial cells (MCs) is an early mechanism of peritoneal dysfunction in peritoneal dialysis (PD). This study was undertaken to investigate the role of Tonsil-derived MSCs (T-MSCs) in TGFβ-induced EMT of human peritoneal mesothelial cells (HPMCs) and its mechanism.

Methods

Transwell co-culture system was used in which MCs were cultured with T-MSCs or T-MSC-conditioned medium (CM). EMT was evaluated by the changes in morphology and markers of epithelial and mesenchymal cells. ROS generation was assessed by DCF-DA and MitoSox^R staining. The effects of T-MSC on the expression of antioxidant enzymes and anti-fibrotic proteins were compared with adipose (AD)-derived MSCs and bone marrow (BM)-derived MSCs. Animal model of PD was established by daily infusion of 4.25% glucose-based dialysate with MGO for 3 weeks via intraperitoneal catheter in Sprague-Dawley rats. T-MSC (5.0x10⁶ cells, i.p.) was injected at 14 days, and peritoneal tissue was isolated in 7 days of T-MSC injection. Markers of oxidative stress and anti-fibrotic were evaluated with peritoneal equilibrium test and histologic analysis.

Results

T-MSC or T-MSC-CM inhibited TGFβ-induced EMT (increased ZO-1 and E-cadherin, decreased αSMA) and oxidative stress (decreased ROS generation). Compared to AD- and BM-MSCs, T-MSCs exhibited higher expression of antioxidant enzymes (catalase, GPx, and SOD) and anti-fibrotic proteins (HGF and BMP-7). T-MSC-CM also restored TGF-β-induced suppression of antioxidant enzymes and anti-fibrotic factors in HPMCs. T-MSC-treated rats had a higher D₂/D₀ glucose and a lower D₂/P₂ creatinine. Anti-human nuclei staining confirmed T-MSC engraftment along the mesothelial layer. T-MSCs alleviated EMT and peritoneal fibrosis with an amelioration of oxidative stress, as evidenced by decreased expression of 8-OHdG, NT, and HNE, along with increased GSH and SOD2.

Conclusion

T-MSCs represent a promising approach to prevent peritoneal fibrosis by providing anti-fibrosis and anti-oxidant effects in the peritoneal cavity and ameliorating the phenotype transition of peritoneal mesothelial cells.

Funding

• Government Support – Non-U.S.

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025g0jrbwft