*Corresponding author: Abolfazl Khajavi Rad. Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Neuroinflammation Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Tel: +98-51-38828565; Fax: +98-51-38828564; E-mail address: khajavirada@mums.ac.ir Iranian Journal of Basic Medical Sciences ijbms.mums.ac.ir In vivo effects of allogeneic mesenchymal stem cells in a rat model of acute ischemic kidney injury Shahrzad Havakhah 1 , Mojtaba Sankian 2 , Gholam Hosein Kazemzadeh 3 , Keyvan Sadri 4 , Hamid Reza Bidkhori 5 , Hojjat Naderi-Meshkin 5 , Alireza Ebrahimzadeh Bideskan 6 , Saeed Niazmand 1, 7 , Abolfazl Khajavi Rad 1, 7 *, Ahmad Reza Bahrami 8 * 1 Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran 2 Immunobiochemistry Lab, Immunology Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran 3 Department of Vascular Surgery, Vascular and Endovascular Surgery Research Center, Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran 4 Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, Iran 5 Stem Cells and Regenerative Medicine Research Group, Iranian Academic Center of Education, Culture and Research (ACECR)-Khorasan Razavi, Mashhad, Iran 6 Microanatomy Research Center, Mashhad University of Medical Sciences, Mashhad, Iran 7 Neuroinflammation Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran 8 Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran A R T I C L E I N F O A B S T R A C T Article type: Original article Objective(s): : Renal ischemia-reperfusion injury (IRI) as a severe condition of acute kidney injury (AKI) is the most common clinical problem with high mortality rates of 35-60% deaths in hospital. Mesenchymal stem cells (MSC) due to unique regenerative characteristics are ideal candidates for the treatment of the ischemic injuries. This work is focused on the administration of MSC to IRI-induced AKI Wistar rats and evaluating their significance in AKI treatment. Material and Methods: Animals underwent surgical procedure and AKI was induced by 40 min bilateral renal pedicle clamping. Immediately after reperfusion, 2×106 rat bone marrow derived MSCs were injected via intra-parenchymal or intra-aortic route. Results: Animals subjected to AKI after days 1 and 3 showed significant increase in the serum creatinine and blood urea nitrogen (BUN) concentration along with a declined glomerular filtration rate (GFR) when compared with non-ischemic animals. On the other hand, treated animals showed a significant enhanced regeneration as compared to ischemic animals in both administration route groups. Conclusion: According to the results concluded from the renoprotective effects of MSC in IRI/AKI, MSCs could be considered as promising therapeutic approach for AKI in clinical applications. Article history: Received: Accepted: Keywords: Acute kidney injury Acute renal failure Bone marrow-derived mesenchymal stem cell Cell transplantation Ischemic kidney injury Rat ►Please cite this article as: Havakhah Sh, Sankian M, Kazemzadeh GhH, Sadri K, Bidkhori HR, Naderi-Meshkin H, Ebrahimzadeh Bideskan AR, Niazmand S, Khajavi Rad A, Bahrami AR. In vivo effects of allogeneic mesenchymal stem cells in a rat model of acute ischemic kidney injury. Iran J Basic Med Sci 2018; 21: Introduction Acute kidney injury (AKI), a heterogeneous clinical syndrome, refers to the progressively kidney failure and declined glomerular filtration rate (GFR) resulting in the accumulation of urea and creatinine in the body. This accumulation of nitrogen wastes results in the impairment of body fluid, electrolytes, and acid-base homeostasis, which is accompanied by significant morbidity and mortality i.e. 23.9% among adults and 13.8% among children. The incidence of AKI among individuals, who have been hospitalized, is significantly greater than the general population (1, 2) and ischemia- reperfusion injury (IRI) has been known as the most common cause of AKI (3). Early diagnosis of AKI is difficult causing irreversible kidney damages in patients, which is being treated with current applied approaches such as dialysis or transplantation (4, 5). Several cell culturing and pre-clinical approaches in animal models are being used to understand the pathophysiology of AKI and finding novel and effective therapeutic strategies (2). Renal IRI is a common experimental model to induce AKI in rat and mice for experimental purposes (2). As per literature, following the induction of renal IRI, the inflammation process is activated and numerous inflammatory mediators such as cytokines, chemokines, and reactive oxygen species (ROS) are secreted and activated, causing recruitment of inflammatory cells for enhanced inflammation leading towards apoptosis and necrosis (4, 6). For these reasons, fundamental strategies and cures are needed for the management and treatment of AKI. Stem cells especially mesenchymal stem cells (MSCs) are undifferentiated cells having self-renewal and multi-lineage differentiation capabilities (5). These cells have been obtained mainly from bone marrow whereas other sources such as umbilical cord, adipose tissue and other less or non-invasive sources and have potential to treat several diseases, including acute