以脂肪幹細胞分泌之微囊泡改善單邊輸尿管結紮造成的腎臟纖維化

鄭如芳¹、鄭劍廷¹、林威佑^1,2

¹國立臺灣師範大學生命科學院、 ²衛生福利部臺北醫院泌尿科

Adipose Stem Cells-Derived Microvesicles Ameliorate Unilateral Ureteral Obstruction-Induced Renal Fibrosis

Ju-Fang Cheng¹、Chiang-Ting Chien¹、Wei-Yu Lin^1,2

¹ Department of Life Science, National Taiwan Normal University, Taipei, Taiwan

²Department of Urology,Taipei Hospital, Ministry of Health and Welfare, New Taipei City, Taiwan

Purpose:

Chronic Kidney Disease (CKD) is the 12th leading death cause worldwide. CKD itself is also a risk factor of many other diseases such as cardiovascular disease. It has high morbidity and mortality, and yet till this day, still without a cure. Adipose-derived stem cells (ADSCs) show to be a promising therapeutic application, and the microvesicles (MVs) from ADSCs have proved to play an important role in ADSC’s effects of immune regulation and damage repairing. Therefore, this study aims to investigate the therapeutic effects of the microvesicles derived from rat ADSCs in a CKD model and to explore the possible mechanisms behind.

Materials and Methods:

In this study, unilateral ureteral obstruction (UUO) model was used as a model of CKD in the in vivo experiments on Wistar rats. Transforming growth factor-β1 (TGF-β1) and erastin were used to induce fibrosis and ferroptosis in a rat kidney epithelial cell line, NRK-52E. MVs were harvested from rat ADSCs and applied via renal artery injection in vivo and directly added to cell media in vitro. Several assays, such as western blotting, immunohistochemistry, and flow cytometry were used to evaluate the therapeutic effects of ADSC-MVs on renal fibrosis.

Results:

Our preliminary results indicated that by treating injured kidney with ADSC-MVs, renal cell deaths were inhibited via the apoptotic and the ferroptotic pathway. Also, ADSC-MVs treatment was able to alleviate renal fibrosis caused by unilateral ureteral obstruction. In the in vitro experiments, similar results can be achieved. ADSC-MVs can significantly attenuate the profibrotic effect caused by TGF-β1 and the ferroptotic cell death induced by Erastin.

Conclusion:

Our study investigates in the therapeutic effects of ADSC-MVs on reducing renal fibrosis in a CKD model both in vivo and in vitro. Our results suggest that ADSC-MVs have great potential to be an alternative treatment to reduce renal fibrosis in CKD.