Early reno-protective antioxidant activity of bone marrow-derived mesenchymal stem cells single dose in renal ischemia-reperfusion in rats

Abstract

Background & Aim Backgrounds/Aims Ischemia-reperfusion injury (IRI) remains one of the leading causes of acute kidney injury (AKI) in both native and transplanted kidneys. Rapid homing of bone marrow derived mesenchymal stem cells (BMSCs) and early Reno-protective activity in IRI reported. We aimed to evaluate an early Reno protective antioxidant activity of a single dose BMSCs against renal IRI and the consequent 14th day functional and histopathological results in rats. Methods, Results & Conclusion Materials and Methods This study was conducted on male Sprague-Dawley. Rats were randomly assigned to three main groups: (1) sham-operated control group; IRI + culture media group, in which rats were subjected to IRI and were administered culture media after 4 hr of IRI; and (3) IRI +BMSCs treated group, in which rats were administered 1 × 106 BMSCs after 4 hr of IRI. Each main group was further divided according to the timing of scarification into four subgroups 6 rats for each to be sacrified at day1, day3, day7 and day14 respectively. Renal function tests; serum creatinine, creatinine clearance and malondialdehyde (MDA) which was determined in the serum and renal tissue. Histopathological changes analyzed in the different regions of the kidney (cortex, outer strip of the outer medulla “OSOM”, inner strip of the outer medulla “ISOM” and inner medulla. In each layer, the scoring system considered active injury changes, regenerative changes and chronic changes separately. Results The BMSCS were defined and their capability of differentiation was proved. When compared to sham-operated rats, IRI resulted in a significant increase in plasma creatinine, serum and tissue MDA and a significant decrease in creatinine clearance. These changes were attenuated by the use of BMSCs. Prominent histopathological injury scores in the cortex, ISOM and OSOM were significantly evident in the positive control group. The use of BMSCs was associated with significantly lowered injury score early at day1 before the development of regenerative activities resulting diminution of the 14th day fibrotic activity. Conclusion BMSCs protect early against renal injury and dysfunction associated with IRI, which suggested to be mediated by an antioxidant activity.