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Stem cells and stem cell-derived extracellular vesicles in acute and chronic kidney diseases: mechanisms of repair.

ABSTRACT: Acute and chronic renal failure have long been described and now renamed as acute kidney injury (AKI) and chronic kidney disease (CKD). New concepts are emerging in the pathophysiology of kidney diseases. AKI is often caused by triggering factors (e.g., toxic, ischemic, immunologic) either individually or combined such as in sepsis (inflammation and hypoxia), and it is initiated at a defined time. Several experimental models of AKI have provided deep insight and have convincingly shown important proof-of-concepts of therapeutic relevance over the years. CKD is now considered a slowly developing disease with often an insidious course, lasting many years whereby co-morbidities (e.g., diabetes, hypertension, dysmetabolic syndrome) may act as worsening factors. It has become increasingly evident that even a single event of AKI may lead to a higher predisposition to develop a progressive CKD. In the present review, we will report studies on the renal protection by adult stem cells in different experimental models and clinical trials. The emerging role of extracellular vesicles (EVs) in cell-to-cell communication and their predominant effect in the paracrine mechanisms of stem cell-dependent actions have prompted several studies on their ability to attenuate both AKI and fibrosis occurring in CKD. We discuss several critical issues that need to be addressed before EVs may have a therapeutic application in humans.

SUBMITTER: Tetta C

PROVIDER: S-EPMC7347774 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Stem cells and stem cell-derived extracellular vesicles in acute and chronic kidney diseases: mechanisms of repair.

Tetta Ciro C Deregibus Maria Chiara MC Camussi Giovanni G

Annals of translational medicine 20200401 8

Acute and chronic renal failure have long been described and now renamed as acute kidney injury (AKI) and chronic kidney disease (CKD). New concepts are emerging in the pathophysiology of kidney diseases. AKI is often caused by triggering factors (e.g., toxic, ischemic, immunologic) either individually or combined such as in sepsis (inflammation and hypoxia), and it is initiated at a defined time. Several experimental models of AKI have provided deep insight and have convincingly shown important ...[more]

PMID: 32775371

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Project description:Abdominal aortic aneurysms (AAA) are localized expansions of the abdominal aorta that develop due to chronic proteolytic disruption of the structural extracellular matrix (ECM) components (elastin and collagen) within the aorta wall. Major limitations in arresting or reversing AAAs lie in naturally poor and aberrant regeneration and repair of elastic matrix structures in the aorta wall. Bone marrow derived mesenchymal stem cells (BM-MSCs) have emerged as a promising regenerative tool and their therapeutic effects are also known to be effected through their paracrine secretions. Extracellular vesicles (EVs) present in these secretions have emerged as critical cellular component in facilitating many therapeutic benefits of MSCs. EV treatment is thus potentially appealing as a stem cell-inspired cell-free approach to avoid possible phenotypic plasticity of MSCs in vivo. In this study, we investigated the thus far unknown effects of BM-MSC derived EVs on vascular elastic matrix repair in the context of AAA treatment. EVs isolated from BM-MSC source were characterized and their pro-regenerative and their anti-proteolytic effects were evaluated on our established in vitro experimental conditions derived from AAA rat model. Our studies revealed the efficacy of BM-MSC derived EVs in attenuating the proteolytic activity and also in imparting elastic matrix regenerative benefits under aneurysmal environment. Interestingly, compared to cell culture conditioned media (CCM), EVs demonstrated superior regenerative and anti-proteolytic benefits in a proteolytic injury culture model of AAA. From these studies, it appears that EVs derived from BM-MSCs could be beneficial in undertaking a reparative effort in AAA induced degeneration of vascular tissue. Statement of Significance Abdominal aortic aneurysms (AAAs) are localized, rupture-prone expansions of the aorta which result from loss of wall flexibility due to enzymatic breakdown of elastic fibers. There are no established alternatives to surgery, which possess high risk for the mostly elderly patients. Our previous studies have established the elastic regenerative and reparative effect of cell culture secretions derived from adult stem cell source. In this study, we propose to isolate extracellular vesicles (exosomes) from these secretions and evaluate their regenerative benefits in AAA smooth muscle cell culture model. This simple and innovative treatment approach has the potential to arrest or reverse AAA growth to rupture, not possible so far.

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Stem cells and stem cell-derived extracellular vesicles in acute and chronic kidney diseases: mechanisms of repair.

Publications

Stem cells and stem cell-derived extracellular vesicles in acute and chronic kidney diseases: mechanisms of repair.

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