Kidney Week

Abstract: SA-PO805

Bone Marrow Mesenchymal Stem Cells (BMSCs) Ameliorate Experimental Renal Interstitial Fibrosis via Promoting Tertiary Lymphoid Organ Neogenesis

Session Information

• Molecular Mechanisms of CKD - III
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 1903 CKD (Non-Dialysis): Mechanisms

Authors

• Zhu, Fengge, Department of Nephrology, Chinese PLA General Hospital, State Key Laboratory of Kidney Diseases, National Clinical Study Center for Kidney Diseases, Beijing, China

Fengge Zhu,

• Chen, Xiangmei, Department of Nephrology, Chinese PLA General Hospital, State Key Laboratory of Kidney Diseases, National Clinical Study Center for Kidney Diseases, Beijing, China

Xiangmei Chen,

• Duan, Shuwei, Department of Nephrology, Chinese PLA General Hospital, State Key Laboratory of Kidney Diseases, National Clinical Study Center for Kidney Diseases, Beijing, China

Shuwei Duan,

• Zheng, Ying, Department of Nephrology, Chinese PLA General Hospital, State Key Laboratory of Kidney Diseases, National Clinical Study Center for Kidney Diseases, Beijing, China

Ying Zheng,

• Bai, Jiuxu, Department of Nephrology, Chinese PLA General Hospital, State Key Laboratory of Kidney Diseases, National Clinical Study Center for Kidney Diseases, Beijing, China

Jiuxu Bai,

Background

Earlier studies indicate that bone marrow mesenchymal stem cells (BMSCs) is effective in protecting experimental renal interstitial fibrosis. However, the exact mechanism is not clear. We purpose that BMSCs may ameliorate renal interstitial fibrosis via promoting renal tertiary lymphoid organ (TLO) neogenesis.

Methods

We establish unilateral ureteral obstruction model using C57/BL6 male mice. BMSCs is given to animals 4 hours after surgery via tail vein, single time, 10⁶ cells per mouse. Animals are sacrificed at the seventh day after surgery and kidney tissues are harvested for histopathological assessment, immunoflurescence staining, immunohistochemistry staining and Western Blotting protein assay.

Results

BMSCs treatment significantly ameliorates renal tubulointerstitial fibrosis and reduce kidney injury score at the 7^th day after UUO surgery. BMSCs treatment also reduces PDGFRβ⁺ fibroblast and α-SMA⁺ myofibroblast infiltration within the kidney, as well as suppresses the renal expression of extracellular matrix proteins collagen I, vimentin and fibronectin. BMSCs treatment also promotes the formation and neogenesis of tertiary lymphoid organ within the kidney, identified with markers PNAd, LYVE-1, and GL-7. Further more, BMSCs treatment significantly inhibits the renal infiltration of CD3e⁺ T lymphocytes, CD11b⁺ monocytes and Ly6C/Ly6G⁺ neutrophils. Our results indicate a possible role of tertiary lymphoid organ formation and leukocyte trafficking in BMSCs' ability to ameliorate kidney injury and interstitial fibrosis.

Conclusion

BMSCs protection from experimental renal tubulointerstitial fibrosis could at least partly be attributed to their promotion of tertiary lymphid organ neogenesis and leukocyte trafficking within the obstructed kidney.

Funding

• Government Support - Non-U.S.