Abstract
Ischemia-reperfusion injury (IRI) plays a significant role in the pathogenesis of acute kidney injury (AKI). The complicated interaction between injured tubular cells, activated endothelial cells, and the immune system leads to oxidative stress and systemic inflammation, thereby exacerbating the apoptosis of renal tubular cells and impeding the process of tissue repair. Stem cell therapy is an innovative approach to ameliorate IRI due to its antioxidative, immunomodulatory, and anti-apoptotic properties. Therefore, it is crucial to understand the biological effects and mechanisms of action of stem cell therapy in the context of acute ischemic AKI to improve its therapeutic benefits. The recent finding that treatment with conditioned medium (CM) derived from stem cells is likely an effective alternative to conventional stem cell transplantation increases the potential for future therapeutic uses of stem cell therapy. In this review, we discuss the recent findings regarding stem cell-mediated cytoprotection, with a focus on the anti-inflammatory effects via suppression of oxidative stress and uncompromised immune responses following AKI. Stem cell-derived CM represents a favorable approach to stem cell-based therapy and may serve as a potential therapeutic strategy against acute ischemic AKI.
Highlights
Acute kidney injury (AKI) involves a complex interaction between the kidney parenchyma and immune system that leads to inflammation at the site of the injured tissue and impaired renal function [1]
We further showed that treatment of induced pluripotent stem cells (iPSCs)-conditioned medium (CM) in rats with ischemia-reperfusion induced AKI (IR-AKI) significantly diminished oxidative stress and protected tubular cells against apoptosis [71], supporting the innovation occurring in this field of research
Animal experiments have provided compelling evidence to support a renoprotective role for stem cells in rescuing IR-AKI
Summary
Acute kidney injury (AKI) involves a complex interaction between the kidney parenchyma and immune system that leads to inflammation at the site of the injured tissue and impaired renal function [1]. Renal ischemia is a significant cause of AKI and is characterized by reduced tissue perfusion, which leads to acute tubular injury. Re-establishing the blood supply after prolonged ischemia activates vascular endothelial cells and enhances the generation of reactive oxygen species (ROS). This triggers a myriad of inflammatory consequences and induces apoptosis of tubular epithelial cells (TECs) [2]. This phenomenon is referred to as ischemia-reperfusion induced AKI (IR-AKI) and is characterized by elevated oxidative stress and activation of the immune system in response to ischemic tissue injury [3,4]. Because stem cells release soluble factors and microvesicles in a paracrine manner [13], we discuss the effectiveness of stem cell-derived conditioned medium (CM) as an alternative to stem cell transplantation in the treatment of IR-AKI
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