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Open Access Research article

Transplantation of endothelial progenitor cells in treating rats with IgA nephropathy

Wei Guo12, Jiang-Min Feng2*, Li Yao2, Li Sun2 and Guang-Qing Zhu3

Author Affiliations

1 Department of Nephrology, The Fourth Hospital of People, Shenyang 110020, China

2 Department of Nephrology, The First Affiliated Hospital of China Medical University, Shenyang 110001, China

3 Department of Meical Ultrasound, The Fourth Hospital of People, Shenyang 110020, China

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BMC Nephrology 2014, 15:110  doi:10.1186/1471-2369-15-110

Published: 9 July 2014

Abstract

Background

Therapeutic options in IgAN are still limited. The aim of this study is to explore the feasibility of using endothelial progenitor cell to treat IgAN in rat model.

Methods

Rat bone marrow mononuclear cells (BM-MNCs) obtained with density gradient centrifugation were cultured in vitro, and induced into endothelial progenitor cells (EPCs). EPCs were identified by surface marker CD34, CD133 and VEGFR2 (FLK-1) and by Dil-Ac-LDL/FITC-UEA-1 double staining. EPCs were labeled with PKH26 prior to transplantation. Rat model of IgAN was established by oral administration of bovine serum albumin together with lipopolysaccharide via the caudal vein and subcutaneous injection of CCL4. Kidney paraffin sections were stained by H&E and PAS. Immunofluorescence was used to assess IgA deposition in the glomeruli. Peritubular capillary (PTC) density was determined by CD31 staining. Monocyte chemoattrant protein-1 (MCP-1), hypoxia-inducible factor-1α (HIF-1α) and CD105 were also measured by immunohistochemistry, western blotting and real-time fluorescent quantitative PCR.

Results

The transplanted BM-EPCs were successfully located in IgAN rat kidney. After transplantation, Urinary red blood cell, urine protein, BUN, Scr and IgA serum level were significantly decreased, so were the areas of glomerular extracellular matrix and the IgA deposition in the glomeruli. In addition, PTC density was elevated. And the expression levels of HIF-1α and MCP-1 were significantly down-regulated, while the expression of CD105 was up-regulated. All these changes were not observed in control groups.

Conclusion

The BM-EPCs transplantation significantly decreases the expansion of glomerular extracellular matrix and the deposition of IgA in the glomeruli; lowers the expression of inflammatory factors; increases PTC density; improves ischemic-induced renal tissue hypoxia, all of which improves the renal function and slows the progress of IgA nephropathy.

Keywords:
Endothelial progenitor cells; IgA nephropathy; Peritubular capillary; Transplantation