Abstract
Introduction: Acute tubular necrosis (ATN) is the most prevalent cause of acute renal failure (ARF). Mesenchymal stem cell transplantation has been studied as a potential treatment for renal dysfunction due to ATN. Inducible nitric oxide synthase (iNOS), bone morphogenetic protein-7 (BMP-7) and B-cell lymphoma 2 (Bcl-2) are surrogate markers of renal tubular epithelial regeneration and subsequent recovery of renal function following ATN. Methods: Serum creatinine (Scr) and blood urea nitrogen (BUN), as well as expression of iNOS, BMP-7 and Bcl-2 in gentamycin-induced ATN rat kidneys was investigated after human umbilical cord-derived mesenchymal stem cell (HUC-MSC) transplantation. Immunohistochemical staining was performed in 3 groups of rats: gentamycin-induced ATN treated with HUC-MSC, gentamycin-induced ATN without HUC-MSC, and untreated rats not receiving any treatments. Results: HUC-MSC transplantation led to a reduction in Scr and BUN in the kidneys of rats with gentamycin-induced ATN. Expression of iNOS in the HUC-MSC treated group occurred later and the expression levels were much lower during gentamycin-induced ATN compared to rats with ATN that were not treated with HUC-MSC. The expression of BMP-7 and Bcl-2 in the MSC-transplanted group was significantly increased compared to both control groups of rats with injured and healthy renal tubules. Conclusions: HUC-MSCs induce renal protection in a rat model of gentamycin-induced ATN, which is associated with reduced iNOS expression and up-regulation of Bcl-2 and BMP-7.
Highlights
Acute tubular necrosis (ATN) is the most prevalent cause of acute renal failure (ARF)
The blood urea nitrogen (BUN) levels increased at 1d in the animals with ATN that received human umbilical cord-derived mesenchymal stem cell (HUC-Mesenchymal stem cells (MSCs)) and those received no cell therapy, peaked at 1 w and returned to normal at 2 w (Table 1)
The BUN levels in gentamycin-treated rats were higher in the untreated group as compared to the HUC-MSC-transplanted group at all time points and the comparison was statistically significant at 1 d, 4 d and 1 w (p < 0.05/3 = 0.0167) (Table 1)
Summary
Acute tubular necrosis (ATN) is the most prevalent cause of acute renal failure (ARF). Mesenchymal stem cell transplantation has been studied as a potential treatment for renal dysfunction due to ATN. Inducible nitric oxide synthase (iNOS), bone morphogenetic protein-7 (BMP-7) and B-cell lymphoma 2 (Bcl-2) are surrogate markers of renal tubular epithelial regeneration and subsequent recovery of renal function following ATN. Methods: Serum creatinine (Scr) and blood urea nitrogen (BUN), as well as expression of iNOS, BMP-7 and Bcl-2 in gentamycin-induced ATN rat kidneys was investigated after human umbilical cord-derived mesenchymal stem cell (HUC-MSC) transplantation. Mesenchymal stem cells (MSCs) promote the renewal of renal tubular epithelial cells and possibly restore renal tubule structure to ameliorate renal injury, which may contribute significantly to the treatment of acute and chronic kidney diseases [6,7]. One study demonstrated a critical role of MSCsecreted insulin-like growth factor 1 (IGF-1) in renal protection, downstream effects of this growth factor are not known [8]
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