Although many efforts have been made to deal with this problem, such as new drugs and modern dialysis techniques, innovative interventions beyond supportive therapy are not available yet[5]; therefore, a potent therapeutic intervention for ischemia AKI is imperative. In recent years, a promising Varespladib price approach to manage renal IRI is the use of mesenchymal stem cells (MSCs). Their use in treating different kind of diseases as immunological, vascular, cardiac and renal diseases has been extensively explored[6,7]. MSCs can be isolated from various sources, such as bone marrow or adipose tissue, but other organs have their

own niches of MSC-like cells, such as the kidney. Besides their broad distribution in the body and an easy isolation, the interest in MSC was originally raised by their capacity to differentiate into other cell types, suggesting that they could be a source of healthy cells to repair/replace injured tissue[8]. There is evidence from both in vitro studies and animal models of AKI that MSCs can promote regenerative responses in the injured kidney, leading to tissue repair and improvement of renal function[9-11]. These beneficial effects have been initially ascribed to the trans-differentiation

of MSCs into organ specific cells. However, at least in the kidney, this is a very rare event and the kidney-protective effects of MSCs have been attributed mainly to paracrine mechanisms[12]. This review will focus on the application of cell therapy in AKI, and it will summarize the recent preclinical and clinical results about the use of MSCs in renal IRI (Figure ​(Figure11). Figure 1 Therapeutic potential of mesenchymal stem cells and their derivatives. MSCs: Mesenchymal stem cells; GDNF: Glial derived-cell line neurotrophic factor; VEGF: Vascular endothelial

growth factor. THERAPEUTIC POTENTIAL OF MESENCHYMAL STEM CELLS Mesenchymal stem cells are undifferentiated adult stem cells derived from mesodermal embryonic layer that can differentiate into a broad range of different mesenchymal tissues, including cartilage, bone, muscle, stroma, fat, tendon, and other connective Entinostat tissues[13]. These cells have been originally isolated from bone marrow where they regulate the self-renewal, maturation and recruitment of hematopoietic stem cells to vascular compartment[14], thanks to their peculiar property to adhere to tissue culture plastic[15]. MSCs are able to in vitro differentiate into cells of mesodermal lineages, such as adipocytes, chondrocytes and osteocytes by the exposure to appropriate conditioning media. A variety of protocols for isolation and expansion are currently used to prepare mesenchymal stem cells for preclinical and clinical use.