Kidney Week

Abstract: SA-PO438

Extracellular Vesicles of Adipose-Derived Stem Cells from Obese Patients Drive ROS-Dependent Premature Senescence in Renal Tubular Cells

Session Information

• Development and Regenerative Medicine
  November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Development, Stem Cells, and Regenerative Medicine

• 500 Development, Stem Cells, and Regenerative Medicine

Authors

• Luo, Ting, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China

Ting Luo,

• Meng, Yu, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China

Yu Meng,

Background

Premature tubular cell senescence is characteristic of obesity-associated renal injury. Extracellular vesicles from adipose-derived stem cells (ADSC-EVs) are highly abundant, while their role in obesity-associated disorders remain unclear. We hypothesized that ADSC-EVs with obese patients were involved in renal tubular cell senescence, possibly via a ROS-dependent pathway.

Methods

ADSCs were isolated from the omental adopts from patients with morbid obesity and healthy volunteers (n=7 each). ADSC-EVs were co-cultured with HK-2 cells. The level of cellular senescence was assessed as senescence-associated β-galactosidase (SA-β-gal) activity using fluorescent quantitative detection, target gene expression using RT-PCR or western blot analysis, and reactive oxygen species (ROS) generation using CMH₂DCFDA staining. The next-generation mRNA sequencing was performed on ADSC-EVs to predict the enriched biological process (DAVID 6.8).

Results

Compared with the control, ADSC-EVs from obesity induced upregulation of SA-β-gal activity, p16^INK4A, TGFβ-1 and α-SMA in HK-2 cells. The mRNA levels of IL-1β, IL-6, and TNF-α also increased (Figure). Totally 56 up-regulated genes were found in ADSC-EVs from the obese compare to the control, and enriched the ROS-related biological processes (Figure). ADSC-EVs from obese patients could induce ROS formation in HK-2 cells. Conversely, ROS inhibitor N-acetylcysteine prevented the premature tubular cell senescence induced by ADSC-EVs from obese patients (Figure).

Conclusion

These findings suggest that EVs from the ex vivo ADSCs of obese patients induce premature tubular cell senescence through a ROS-mediated mechanism. Targeting ADSC-EV shedding may provide opportunities to limit the dysfunction of renal tubular cell post-obesity.

Figure

Funding

• Government Support - Non-U.S.