Extracellular micro/nanovesicles rescue kidney from ischemia‐reperfusion injury

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 pathophysiology of renal IRI is unknown, the role of inflammatory responses has been elucidated. Because mesenchymal stromal cells (MSCs) have strong immunomodulatory 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.

Extracellular vesicles for acute kidney injury in preclinical rodent models: a meta-analysis

“…However, the prognosis of this disease, which may occur under various circumstances, has not been significantly improved since the mid-1990s [2]. Due to the lack of efficient therapeutic methods, patients with renal ischaemia reperfusion injury (IRI) are mostly treated by supportive manoeuvres, such as renal replacement therapy [3].…”

“…Recently, data in the literature have highlighted that the delivery of MSC-derived EVs can ameliorate AKI in preclinical models [3, 6, 8]. EVs are secreted by almost all types of cells and can be subdivided into exosomes, microvesicles, and apoptotic bodies [9].…”

“…EVs contain proteins, lipids, carbohydrates, mRNAs, and miRNAs and may influence different cell types acting on physiological processes such as proliferation and immune escape [11]. Compared with MSCs, the small size of MSC-derived EVs allows them to avoid the pulmonary first-pass effect and to penetrate deep inside most body barriers [3]. Therefore, MSC-derived EVs are expected to be an effective treatment for AKI.…”

“…Many animal studies have been performed to investigate the efficacy of EVs on an AKI model with various cell origins and different injection doses, delivery routes, and therapy times [3, 12]. To provide the most recent available evidence for clinical studies, we performed this meta-analysis to investigate the efficacy of EVs on preclinical rodent models.…”

Mesenchymal Stromal Cells’ Therapy for Polyglutamine Disorders: Where Do We Stand and Where Should We Go?

“…In 2010, the therapeutic potential of MSC-derived EVs was tested in a mouse model of ischemia (Lai et al, 2010 ). Since then, EVs have been investigated in several other disease models, such as cardiovascular disorders (Wang N. et al, 2017 ), kidney injury (Aghajani Nargesi et al, 2017 ; Farzamfar et al, 2019 ), immune diseases (Lai et al, 2018 , 2019 ), tumor growth (Wu et al, 2013 ; Zhang et al, 2017 ) and neurological diseases (Wang et al, 2018 ; Gorabi et al, 2019 ), obtaining encouraging results (Yu et al, 2014 ).…”