Mesenchymal Stem Cell-Derived Extracellular Vesicles: A Potential Therapeutic Strategy for Acute Kidney Injury

Abstract

Acute kidney injury (AKI) is a common and potential life-threatening disease in patients admitted to hospital, affecting 10%–15% of all hospitalizations and around 50% of patients in the intensive care unit. Severe, recurrent, and uncontrolled AKI may progress to chronic kidney disease or end-stage renal disease. AKI thus requires more efficient, specific therapies, rather than just supportive therapy. Mesenchymal stem cells (MSCs) are considered to be promising cells for cellular therapy because of their ease of harvesting, low immunogenicity, and ability to expand in vitro. Recent research indicated that the main therapeutic effects of MSCs were mediated by MSC-derived extracellular vesicles (MSC-EVs). Furthermore, compared with MSCs, MSC-EVs have lower immunogenicity, easier storage, no tumorigenesis, and the potential to be artificially modified. We reviewed the therapeutic mechanism of MSCs and MSC-EVs in AKI, and considered recent research on how to improve the efficacy of MSC-EVs in AKI. We also summarized and analyzed the potential and limitations of EVs for the treatment of AKI to provide ideas for future clinical trials and the clinical application of MSC-EVs in AKI.

Klotho and Mesenchymal Stem Cells: A Review on Cell and Gene Therapy for Chronic Kidney Disease and Acute Kidney Disease

“…Studies have demonstrated, for example, that in comparison with sham controls, in which the vesicles accumulate mainly in the liver, the damaged tissue uptakes the MSC-EVs more efficiently [296,297]. Furthermore, the treatment mitigates AKI in a dose-dependent manner through the reduction of serum creatinine levels, interstitial infiltrate and apoptosis, as well as through the promotion of tubular cell proliferation and antioxidant effects [296,298].…”

Potential Therapeutic Effect and Mechanisms of Mesenchymal Stem Cells-Extracellular Vesicles in Renal Fibrosis

“…They have pro-angiogenic, immunosuppressive, and anti-fibrotic properties ( Farge et al, 2021 ), inhibit inflammation, and promote tissue repair ( Shi et al, 2018 ). In addition, MSCs are easy to harvest, have low immunogenicity and can be expanded in vitro , all characteristics of a cell population capable of treating organ fibrosis ( Li et al, 2021 ). However, MSC therapy requires cell transplantation, which could possess safety problems ( Zhang et al, 2020 ; Racchetti and Meldolesi, 2021 ), such as cell rejection, unexpected immune responses, toxicity, carcinogenicity, and viral contamination, as well as the need for cell transportation and storage before transplantation ( Lelek and Zuba-Surma, 2020 ), which therefore limit the application of MSCs.…”

“…MSC-EVs are able to transfer functional proteins and genetic material directly to recipient cells, achieving the same therapeutic effect as MSCs ( Wang et al, 2020a ; Thalakiriyawa et al, 2021 ). On the other hand, compared with MSCs, MSC-EVs have lower immunogenicity, easy preservation, and the potential for being artificially modified ( Li et al, 2021 ), and lack potentially dangerous properties, such as self-replication, ectopic differentiation, tumor formation, and genetic instability ( Jafarinia et al, 2020 ). Therefore, MSC-EVs can replace MSCs in the treatment of inflammation and immune-related diseases ( Wang et al, 2020a ), such as organ fibrosis ( Huang and Yang, 2021 ).…”

Fatty Acid β-Oxidation in Kidney Diseases: Perspectives on Pathophysiological Mechanisms and Therapeutic Opportunities

“…Several reports have demonstrated that mesenchymal stem cells (MSCs) and their constituents, extracellular vesicles (EVs), are a novel therapeutic target for kidney diseases ( Yea et al, 2021 ; Li et al, 2021a ; Peng et al, 2022 ). Recently, it has been demonstrated that MSCs and MSC-EVs can regulate the lipid metabolism by increasing the expression of FAO-related genes and reducing fatty acid uptake (CD36) in metabolic diseases ( Li et al, 2019a ; El-Derany and AbdelHamid, 2021 ).…”