title: Protective effect of adipose-derived mesenchymal stem cells against acute kidney injury induced by ischemia-reperfusion in Sprague-Dawley rats.
abstract: Acute kidney injury (AKI) is a complex clinical condition associated with significant morbidity and mortality and lacking effective management. Ischemia-reperfusion injury (IRI) remains one of the leading causes of AKI in native and transplanted kidneys. The aim of this study was to evaluate the efficacy of adipose-derived mesenchymal stem cells (ADSCs) in the prevention of renal IRI in rats. The study was conducted on male Sprague-Dawley rats (n=72) weighing 250-300 g. Rats were randomly assigned to three main groups: i) Sham-operated control group (n=24); ii) positive control group, in which rats were subjected to IRI and were administered culture media following 4 h of IRI (n=24); and iii) ADSC group (n=24), in which rats were administered 1×106ADSCs via the tail vein following 4 h of IRI. Each main group was further divided according to the timing after IRI into four equal-sized subgroups. Renal function was tested via the measurement of serum creatinine levels and creatinine clearance. In addition, malondialdehyde (MDA) levels were determined in serum and renal tissue homogenate as an indicator of oxidative stress. Histopathological changes were analyzed in different regions of the kidney, namely the cortex, outer stripe of the outer medulla (OSOM), inner stripe of the outer medulla (ISOM) and inner medulla. In each region, the scoring system considered active injury changes, regenerative changes and chronic changes. The ADSCs were assessed and their differentiation capability was verified. IRI resulted in a significant increase in serum creatinine, serum and tissue MDA levels and a significant reduction in creatinine clearance compared with those in sham-operated rats,. These changes were attenuated by the use of ADSCs. The prominent histopathological changes in the cortex, ISOM and OSOM were reflected in the injury score, which was significantly evident in the positive control group. The use of ADSCs was associated with significantly lowered injury scores at days 1 and 3; however, no significant effect was observed on day 7. These results indicate that the use of ADSCs ameliorates renal injury and dysfunction associated with IRI in rats.
authors.affiliation: Urology and Nephrology Center, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.
authors.forename: Hussein
authors.initials: H
authors.lastname: Sheashaa
authors.affiliation: Medical Experimental Research Center (MERC), Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Lotfy
authors.affiliation: Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.
authors.forename: Fatma
authors.initials: F
authors.lastname: Elhusseini
authors.affiliation: Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.
authors.forename: Azza Abdel
authors.initials: AA
authors.lastname: Aziz
authors.affiliation: Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.
authors.forename: Azza
authors.initials: A
authors.lastname: Baiomy
authors.affiliation: Medical Experimental Research Center (MERC), Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.
authors.forename: Samah
authors.initials: S
authors.lastname: Awad
authors.affiliation: Medical Experimental Research Center (MERC), Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.
authors.forename: Aziza
authors.initials: A
authors.lastname: Alsayed
authors.affiliation: Department of Public Health, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.
authors.forename: Abdel-Hady
authors.initials: AH
authors.lastname: El-Gilany
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.
authors.forename: Mohamed-Ahdy A A
authors.initials: MA
authors.lastname: Saad
authors.affiliation: Urology and Nephrology Center, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.
authors.forename: Khaled
authors.initials: K
authors.lastname: Mahmoud
authors.affiliation: Biochemistry Department, Faculty of Science, Zagazig University, Zagazig 44516, Egypt.
authors.forename: Faten
authors.initials: F
authors.lastname: Zahran
authors.affiliation: Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.
authors.forename: Dalia A
authors.initials: DA
authors.lastname: Salem
authors.affiliation: Urology and Nephrology Center, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Sarhan
authors.affiliation: Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.
authors.forename: Hassan Abdel
authors.initials: HA
authors.lastname: Ghaffar
authors.affiliation: Urology and Nephrology Center, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt; Medical Experimental Research Center (MERC), Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Sobh
keywords: acute kidney injury; adipose derived mesenchymal stem cell; ischemia reperfusion injury; rats