Abstract: TH-PO311

The Protective Effect of Transplanting Bone Marrow Mesenchymal Stem Cells with Over Expressed Klotho Gene for Kidney Injury

Session Information

Category: Acute Kidney Injury

  • 001 AKI: Basic

Authors

  • Wan, Xin, Nanjing Hospital Affiliated to Nanjing Medical University (Nanjing First Hospital), Nanjing, China
  • Cao, Changchun, Sir Run Run Hospital Affiliated to Nanjing Medical University, Nanjing, JIANGSU , China
Background

The bone marrow mesenchymal stem cell (BMSC) is a kind of cell with multi-directional differentiation ability and has potent immuno-regulation ability which was confirmed in alleviating acute kidney injury(AKI). Klotho is a protein associated with aging and thought as an antagonist of Wnt/β-catenin pathways which can induce renal fibrosis. Thus a hypothesis was make that modify BMSCs with over expressed Klotho gene and then transplant the BMSCs to individuals with AKI can protect the kidney more efficiency.

Methods

BMSCs was isolated from mice and was cultured to the third generation, the BMSCs were transfected with adenovirus carrying Klotho gene in three days and harvested Klotho-BMSCs. A total of 18 healthy C57BL/6 male mice were used to establish renal IRI model by clamping unilateral renal pedicle for 60 minutes followed by reperfusion. The IRI mice were divided into three groups which was transplanted with PBS, BMSCs and Klotho-BMSCs separately. Kidney tissue and blood samples were collected at 3,14 days after AKI.Renal histological changes were estimated by HE staining and Masson staining.The expression of collagen III and IDO were determined by immunohistochemistry, the location of CD68 was observed by immunofluorescence.

Results

Compared with normal mice, classical tubular damage was found in IRI groups,accompanied by a lot of macrophage infiltrate.The mice transplant with Klotho-BMSCs have the lowest BUN and Cr serum level, while the PBS injected mice have the highest BUN and Cr serum level. The extent of kidney fibrosis at 14 days showed that the Klotho-BMSCs group was the mildest while the fibrosis of BMSCs group was better than PBS group.Compared with normal groups, the injury kidney expressed CD68 significantly which means macrophage infiltrated in kidney, and the infiltration was downregulated by transplanting BMSCs or Klotho-BMSCs. In vivo, Klotho-BMSCs showed more obviously proliferative capacity compared with BMSCs, while the Wnt pathway was significantly suppressed in Klotho-BMSCs.

Conclusion

Over expression of Klotho in BMSCs can improve the proliferative capacity of the BMSCs. That leads to potent down-regulated effect to macrophage cells. At the same time, secrete Klotho is an antagonism to kidney fibrosis. So Klotho-BMSCs exhibit synergistic effect and it can be a new medicine in therapy of kidney fibrosis after AKI.