Received: 21 September 2018 | Accepted: 3 December 2018 DOI: 10.1002/jcp.27998 REVIEW ARTICLE Extracellular micro/nanovesicles rescue kidney from ischemia‐reperfusion injury Saeed Farzamfar 1 | Akram Hasanpour 2 | Niloufar Nazeri 2 | Hengameh Razavi 1 | Majid Salehi 3,4 | Shilan Shafei 5 | Vajiheh T. Nooshabadi 6 | Ahmad Vaez 1 | Arian Ehterami 7 | Hamed Sahrapeyma 8 | Jafar Ai 1 1 Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran 2 Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran 3 Department of Tissue Engineering, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran 4 Tissue Engineering and Stem Cells Research Center, Shahroud University of Medical Sciences, Shahroud, Iran 5 Department of Molecular Medicine, School of Advanced Technologies in Medicine, International Campus of Tehran University of Medical Sciences, Tehran, Iran 6 Department of Applied Cell Sciences, Kashan University of Medical Sciences, Kashan, Iran 7 Department of Mechanical and Aerospace Engineering, Science and Research Branch, Islamic Azad University, Tehran, Iran 8 Department of Biomaterial Engineering, Science and Research Branch, Islamic Azad University, Tehran, Iran Correspondence Jafar Ai, Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. Email: jafar_ai@tums.ac.ir Majid Salehi, Department of Tissue Engineering, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran. Email: salehi.m@shmu.ac.ir Abstract Acute renal failure (ARF) is a clinical challenge that is highly resistant to treatment, and its high rate of mortality is alarming. Ischemia–reperfusion injury (IRI) is the most common cause of ARF. Especially IRI is implicated in kidney transplantation and can determine graft survival. Although the exact pathophy- siology of renal IRI is unknown, the role of inflammatory responses has been elucidated. Because mesenchymal stromal cells (MSCs) have strong immunomo- dulatory properties, they are under extensive investigation as a therapeutic modality for renal IRI. Extracellular vesicles (EVs) play an integral role in cell‐ to‐cell communication. Because the regenerative potential of the MSCs can be recapitulated by their EVs, the therapeutic appeal of MSC‐derived EVs has dramatically increased in the past decade. Higher safety profile and ease of preservation without losing function are other advantages of EVs compared with their producing cells. In the current review, the preliminary results and potential of MSC‐derived EVs to alleviate kidney IRI are summarized. We might be heading toward a cell ‐free approach to treat renal IRI. KEYWORDS exosomes, extracellular vesicles (EVs), ischemia‐reperfusion injury (IRI), microvesicles (MVs), renal failure 1 | INTRODUCTION Acute renal failure (ARF) is a clinical challenge that is highly resistant to treatment, and its high rate of mortality is alarming (Rodríguez et al., 2017). ARF is a syndrome characterized by a rapid decline in kidney function, resulting from a number of different causes (van Spil, Steenbergen, & Verhave, 2016; Yalavarthy, Edelstein, & Teitelbaum, 2007). Ischemia‐reperfusion injury (IRI) is the most common cause for this condition (Malek & Nematbakhsh, 2015). The term ischemia‐ reperfusion describes a situation in which blood supply returns to the tissue after a period of insufficient perfusion (Sanderson, Reynolds, Kumar, Przyklenk, & Hüttemann, 2013). Reperfusion of ischemic tissue J Cell Physiol. 2018;1–11. wileyonlinelibrary.com/journal/mar © 2018 Wiley Periodicals, Inc. | 1