Kidney Week

Abstract: TH-PO416

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

Session Information

• Development, Organoids, Injury, and Regeneration
  October 24, 2024 | 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, Ewha Womans University College of Medicine, Seoul, Korea (the Republic of)

Duk-Hee Kang, MD, PhD

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

Dal-Ah Kim, PhD

• Jo, Chor ho, Ewha Womans University College of Medicine, Seoul, Korea (the Republic of)

Chor ho Jo, PhD

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 (T-MSC-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. Animal model of PD was established by daily infusion of 4.25% glucose-based dialysate with methylglyoxal for 3 weeks via intraperitoneal catheter in Sprague-Dawley rats. T-MSC (1.0 x 10⁷cells, i.p.) was injected at 14 days of catheter insertion, and peritoneal tissue was isolated in 7 days of T-MSC injection. Markers of oxidative stress, ER-stress, apoptosis, and NLRP3 inflammasome were evaluated with peritoneal equilibrium test (PET) and histologic analysis.

Results

Co-culture of HPMCs and T-MSC or T-MSC-CM inhibited TGFβ-induced EMT (increased ZO-1 and E-cadherin and decreased αSMA) and oxidative stress (decreased ROS generation). In PD, T-MSCs alleviated EMT and peritoneal fibrosis and reduced Bax, cleaved caspase and increased Bcl-2, and also decreased 8-OHdG with an increase in GSH and SOD2. T-MSC led to a decrease in proteins of ER stress and NLRP3 inflammasome. T-MSCs treated rats had a higher D₂/D₀ glucose and a lower D₂/P₂ creatinine. Anti-human nuclei staining revealed scattered positive staining along peritoneal mesothelial layer.

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.