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Kidney Week

Abstract: FR-PO363

Effects of Bone Marrow Mesenchymal Stem Cell-Derived Exosomes on Renal Fibrosis by Regulating Macrophage Phenotypic Transformation

Session Information

  • CKD: Mechanisms - II
    November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Author

  • Chen, Xiaolan, The Affiliated Hospital of Nantong university, Nantong, China
Background

In recent years, bone marrow mesenchymal stem cells (BM-MSCs) have received extensive attention due to their biological characteristics such as self-replication, high proliferative potential and multi-directional differentiation . This hinders the clinical transformation of MSCs in the treatment of kidney disease. Recent studies have shown that homing of MSCs to the injury site in the circulatory system is not the main mechanism for their continued therapeutic effects.

Methods

Establishment of unilateral ureteral obstruction (UUO) model in mice and random grouping: (1) sham operation group; (2)UUO group; (3)UUO+PBS group; (4)UUO+MSC(1×106/animal); (5)UUO+ exosomes (30μg/animal) group. Stem cells and exosomes were injected intravenously in the caudal vein on the day of modeling.Specimen collection and detection: HE staining and Masson staining were used to detect the pathological changes of renal tissue in each group of mice. Western Blot was used to detect the expression of α-SMA protein . Immunohistochemistry was used to detect renal interstitial fibrosis, macrophage infiltration and phenotype in each group. Flow cytometry was used to detectmacrophage subtypes.

Results

In vivo: Compared with UUO group, the renal pathology of the two groups of mice intervened by MSC and exosomes tail vein injection was significantly improved. the expression level of CD86 was significantly decreased after MSC and exosomes intervention, while the expression level of CD206 was increased;the ratio M2/M1 of macrophage subtypes in MSC and exosomes intervention groups was significantly increased.In vitro: the proliferation ability of macrophages in LPS group was significantly decreased. the secretion of IL-12 by macrophages in LPS group increased significantly, but the secretion of IL-10 did not change significantly(P>0.05).the expression of iNOS and ARG1mRNA in LPS group increased . Compared with LPS group, the proliferation ability of macrophages increased after exosomes intervention. the expression of IL-12 decreased and the expression of IL-10 increased after exosome intervention. iNOSmRNA expression was down-regulated and ARG1mRNA expression was up-regulated after exosomes intervention.

Conclusion

Exosomes derived from bone marrow mesenchymal stem cells can regulate macrophage phenotypic transformation, thus improving renal fibrosis.