Limits...
Transplantation of endothelial progenitor cells in treating rats with IgA nephropathy.

Guo W, Feng JM, Yao L, Sun L, Zhu GQ - BMC Nephrol (2014)

Bottom Line: 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.And the expression levels of HIF-1α and MCP-1 were significantly down-regulated, while the expression of CD105 was up-regulated.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Nephrology, The First Affiliated Hospital of China Medical University, Shenyang 110001, China. fengjiangm@163.com.

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.

Show MeSH

Related in: MedlinePlus

Representative images of histological staining of renal sections. The renal sections were stainied by H&E staining (A, B, C) , PAS staining (D, E, F) and Immunofluorescence staining for IgA (G, H, I), respectively. Normal group, there was no significant histological abnormality after saline solution injection (A, D, G), IgAN group after saline solution injection, the pathological changes were increased number of cells in the glomeruli, and moderate to severe hyperplasia of mesangial matrix and cells. There was significiant green fluorescence in the glomeruli. (B, E, H). EPCs group after EPCs transplantation, hyperplasia of mesangial matrix and cells was decreased, green fluorescence in the glomeruli was weaken than IgAN group, (C, F, I).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4109798&req=5

Figure 5: Representative images of histological staining of renal sections. The renal sections were stainied by H&E staining (A, B, C) , PAS staining (D, E, F) and Immunofluorescence staining for IgA (G, H, I), respectively. Normal group, there was no significant histological abnormality after saline solution injection (A, D, G), IgAN group after saline solution injection, the pathological changes were increased number of cells in the glomeruli, and moderate to severe hyperplasia of mesangial matrix and cells. There was significiant green fluorescence in the glomeruli. (B, E, H). EPCs group after EPCs transplantation, hyperplasia of mesangial matrix and cells was decreased, green fluorescence in the glomeruli was weaken than IgAN group, (C, F, I).

Mentions: Morphology of glomerular, tubular, and renal interstitial remainined normal in normal group. While, in IgAN groups, the number of glomerular mesangial cells increased, mesangial matrix widened, the shape of renal tubules became irregular. In EPCs group, pathological changes of renal mesangial matrix and tubules were significantly alleviated (shown in Figure 5).


Transplantation of endothelial progenitor cells in treating rats with IgA nephropathy.

Guo W, Feng JM, Yao L, Sun L, Zhu GQ - BMC Nephrol (2014)

Representative images of histological staining of renal sections. The renal sections were stainied by H&E staining (A, B, C) , PAS staining (D, E, F) and Immunofluorescence staining for IgA (G, H, I), respectively. Normal group, there was no significant histological abnormality after saline solution injection (A, D, G), IgAN group after saline solution injection, the pathological changes were increased number of cells in the glomeruli, and moderate to severe hyperplasia of mesangial matrix and cells. There was significiant green fluorescence in the glomeruli. (B, E, H). EPCs group after EPCs transplantation, hyperplasia of mesangial matrix and cells was decreased, green fluorescence in the glomeruli was weaken than IgAN group, (C, F, I).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4109798&req=5

Figure 5: Representative images of histological staining of renal sections. The renal sections were stainied by H&E staining (A, B, C) , PAS staining (D, E, F) and Immunofluorescence staining for IgA (G, H, I), respectively. Normal group, there was no significant histological abnormality after saline solution injection (A, D, G), IgAN group after saline solution injection, the pathological changes were increased number of cells in the glomeruli, and moderate to severe hyperplasia of mesangial matrix and cells. There was significiant green fluorescence in the glomeruli. (B, E, H). EPCs group after EPCs transplantation, hyperplasia of mesangial matrix and cells was decreased, green fluorescence in the glomeruli was weaken than IgAN group, (C, F, I).
Mentions: Morphology of glomerular, tubular, and renal interstitial remainined normal in normal group. While, in IgAN groups, the number of glomerular mesangial cells increased, mesangial matrix widened, the shape of renal tubules became irregular. In EPCs group, pathological changes of renal mesangial matrix and tubules were significantly alleviated (shown in Figure 5).

Bottom Line: 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.And the expression levels of HIF-1α and MCP-1 were significantly down-regulated, while the expression of CD105 was up-regulated.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Nephrology, The First Affiliated Hospital of China Medical University, Shenyang 110001, China. fengjiangm@163.com.

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.

Show MeSH
Related in: MedlinePlus