Abstract

Acute renal failure has a 50% - 80% mortality rate. Currently, treatment options for this life-threatening disease are limited. Low-level laser therapy (LLLT) has been found to modulate biological activity. The aim of the present study was to investigate the possible beneficial effects of laser application to stem cells in the bone marrow, on the kidneys of rats that had undergone ischemia-reperfusion injury (IRI). IRI was induced by occlusion of the renal artery to 3- and 7-month-old rats for 15 or 30 minutes. In an additional experiment IRI was applied to both kidneys for 20 min each in 2-3-month-old rats. Rats were then divided randomly into two groups of control and laser-treated. Laser therapy (Ga-Al-As 810 nm, 200 mW output for 2 min) was applied to the bone marrow 1 and 7 days post-IRI to the kidneys, and rats were sacrificed 2 weeks later. Histomorphometry and immunohistochemistry were performed on kidney sections and blood markers for kidney function. Quantitative histomorphometric analysis revealed a reduction in dilatation of the renal tubules, restored structural integrity of the renal tubules, and reduced necrosis in the laser-treated rats as compared to the control, non-laser-irradiated group. C-kit positive cell density in kidneys post-IRI and laser-treatment was significantly (p = 0.015) 3.2-fold higher compared to the control group. Creatinine and blood urea nitrogen content were significantly lower in the laser-treated rats as compared to control. It is concluded that LLLT application to the bone marrow (BM) causes a significant increase in the density of mesenchymal stem cells in the kidneys post-IRI, probably by induction of stem cells in the BM, which subsequently migrate to the IRI kidney, significantly reducing the pathological features of the kidney and increasing kidney function post IRI.

Highlights

  • Acute kidney injury (AKI) is a common clinical issue with high morbidity and mortality

  • In the group of 2-3-month-old rats the histopathological changes visible in the control, non-laser-treated, histological sections consisted mainly in tubular dilatation, loss of contour of those tubules, and necrosis, as well as some blood cells in the interstitial tissue of the kidney (Figure 1). In those rats that received level laser therapy (LLLT) to the bone marrow (BM) post-ischemia/reperfusion injury (IRI) to the kidney, the contour of renal tubules remained clear, almost no tubular dilatation was observed, and necrosis was barely discernible

  • The present study indicates that LLLT has reno-protective effects post moderate IRI to the rat kidney

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Summary

Introduction

Acute kidney injury (AKI) is a common clinical issue with high morbidity and mortality. Cell-based therapy offers an exciting potential for kidney regeneration [1]-[10] In both mice and humans there is evidence that cells of bone marrow (BM) origin take part in tubular epithelium regeneration [1]. The evidence that mesenchymal stem cells, by virtue of their reno-protective property, restore renal tubular structure and renal function during experimental acute renal failure, offers the potential for therapeutic intervention [1]. In addition to the contribution to kidney repair by bone-marrow-derived stem cells, and putative renal tubular epithelial stem cells, the original hypothesis still stands that viable tubular epithelial cells that have survived the ischemic insult, proliferate and thereby generate new tubular epithelial cells that replace the damaged ones [4]. The involvement of c-kit in the above processes was established

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