PSC-MSC-Derived Exosomes Protect against Kidney Fibrosis In Vivo and In Vitro through the SIRT6/ β-Catenin Signaling Pathway

Int J Stem Cells. 2021 Aug 30;14(3):310-319. doi: 10.15283/ijsc20184.

Abstract

Background and objectives: Chronic kidney disease (CKD) has a major impact on the quality of life of patients, and renal fibrosis is a critical pathological change in the disease. It is very important to control the process of renal fibrosis to improve the quality of life of patients with CKD. The pathological mechanism of renal fibrosis is very complicated, and the current treatment strategy also has many flaws.

Methods and results: To explore a better treatment, we collected exosomes from pluripotent stem cell (PSC)-derived mesenchymal stem cells (MSC) and verified their therapeutic effect on renal fibrosis through in vivo and in vitro experiments. In this study, we found that PSC-MSC-derived comes could prevent the epithelial differentiation of NRK-52E cells, and with increasing exosome concentrations, the effect was improved. Furthermore, PSC-MSC-derived exosomes could reduce the pathological process of renal fibrosis, reduce inflammatory reactions and improve renal function in UUO mice. Moreover, the protective effect of exosomes against renal fibrosis may be achieved by increasing the expression of SIRT6 and decreasing the expression of β-catenin and its downstream products.

Conclusions: These findings suggest the possibility of PSC-MSC-derived exosomes as a new, effective therapeutic tool for kidney fibrosis.

Keywords: Exosomes; Renal fibrosis; SIRT6; UUO.