Human umbilical cord perivascular cells-derived extracellular vesicles mediate the transfer of IGF-I to the liver and ameliorate hepatic fibrogenesis in mice

Fiore, Esteban; Domínguez, Luciana; Bayo, Juan; Malvicini, Mariana; Atorrasagasti, Catalina; Rodríguez, Marcelo M.; Cantero, María José; Garcı́a, Mariana; Yannarelli, Gustavo; Mazzolini, Guillermo

doi:10.1038/s41434-019-0102-7

Cited by 27 publications

(29 citation statements)

References 35 publications

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“…EVs from human tonsil-derived mesenchymal stromal cells reduced expression of αSMA , TGF-β , CCN2 and vimentin in human LX2 HSC in vitro and attenuated collagen deposition and profibrotic gene expression in CCl 4 -induced liver fibrosis in mice, with the therapeutic effect attributed to elevated levels of EV miR-486-5p which suppressed Smo Hh receptor expression and signaling in HSC [ 281 ]. EVs from human umbilical cord perivascular cells were antifibrotic and inhibited fibrosis-related gene expression in TAA-induced hepatic fibrosis in vivo but these effects were augmented upon prior loading of the EVs with IGF-1 by adenoviral transduction of the donor cells [ 282 ]. These EVs were also inhibitory for fibrogenesis in HSC in vitro as well as modulating inflammatory mediators (iNOS, arginase, IL-6, TNF-α) in cultured macrophages [ 282 ].…”

Section: Hepatic Fibrosismentioning

confidence: 99%

“…EVs from human umbilical cord perivascular cells were antifibrotic and inhibited fibrosis-related gene expression in TAA-induced hepatic fibrosis in vivo but these effects were augmented upon prior loading of the EVs with IGF-1 by adenoviral transduction of the donor cells [ 282 ]. These EVs were also inhibitory for fibrogenesis in HSC in vitro as well as modulating inflammatory mediators (iNOS, arginase, IL-6, TNF-α) in cultured macrophages [ 282 ].…”

Section: Hepatic Fibrosismentioning

confidence: 99%

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Extracellular Vesicles in Organ Fibrosis: Mechanisms, Therapies, and Diagnostics

Brigstock

2021

Cells

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Fibrosis is the unrelenting deposition of excessively large amounts of insoluble interstitial collagen due to profound matrigenic activities of wound-associated myofibroblasts during chronic injury in diverse tissues and organs. It is a highly debilitating pathology that affects millions of people globally and leads to decreased function of vital organs and increased risk of cancer and end-stage organ disease. Extracellular vesicles (EVs) produced within the chronic wound environment have emerged as important vehicles for conveying pro-fibrotic signals between many of the cell types involved in driving the fibrotic response. On the other hand, EVs from sources such as stem cells, uninjured parenchymal cells, and circulation have in vitro and in vivo anti-fibrotic activities that have provided novel and much-needed therapeutic options. Finally, EVs in body fluids of fibrotic individuals contain cargo components that may have utility as fibrosis biomarkers, which could circumvent current obstacles to fibrosis measurement in the clinic, allowing fibrosis stage, progression, or regression to be determined in a manner that is accurate, safe, minimally-invasive, and conducive to repetitive testing. This review highlights the rapid and recent progress in our understanding of EV-mediated fibrotic pathogenesis, anti-fibrotic therapy, and fibrosis staging in the lung, kidney, heart, liver, pancreas, and skin.

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Section: Hepatic Fibrosismentioning

confidence: 99%

Section: Hepatic Fibrosismentioning

confidence: 99%

Extracellular Vesicles in Organ Fibrosis: Mechanisms, Therapies, and Diagnostics

Brigstock

2021

Cells

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“…In addition, UC-MSC-EVs reduced the mRNA expression of pro-inflammatory cytokines TNF-α, IL-1β, and IFN-gamma in schistosome-infected liver tissue. Also, EVs obtained from UC-PVCs can effectively reduce both fibrosis and inflammation in a TAA-induced model of chronic liver injury (Fiore et al, 2020). Interestingly, EVs derived from UC-PVCs that were transduced by an adenovirus vector to produce human IGF-1 exhibited a stronger anti-fibrotic effect with respect to their green fluorescent protein (GFP)transfected counterpart.…”

Section: Msc-ev Effects In Liver Fibrosismentioning

confidence: 99%

Molecular Pathways Modulated by Mesenchymal Stromal Cells and Their Extracellular Vesicles in Experimental Models of Liver Fibrosis

Chiabotto

Pasquino

Camussi

et al. 2020

Front. Cell Dev. Biol.

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End-stage liver fibrosis is common to all chronic liver diseases. Since liver transplantation has several limitations, including lack of donors, immunological rejection, and high medical costs, therapeutic alternatives are needed. The administration of mesenchymal stromal cells (MSCs) has been proven effective in tissue regeneration after damage. However, the risk of uncontrolled side effects, such as cellular rejection and tumorigenesis, should be taken into consideration. A safer alternative to MSC transplantation is represented by the MSC secretome, which retains the same beneficial effect of the cell of origin, without showing any considerable side effect. The paracrine effect of MSCs is mainly carried out by secreted particles in the nanometer range, known as extracellular vesicles (EVs) that play a fundamental role in intercellular communication. In this review, we discuss the current literature on MSCs and MSC-EVs, focusing on their potential therapeutic action in liver fibrosis and on their molecular content (proteins and RNA), which contributes in reverting fibrosis and prompting tissue regeneration.

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“…Interestingly, MSC-EVs express CCR2 chemokine, bind and reduce the concentration of the free pro-inflammatory CCL2 ligand, and therefore prevent the activation and recruitment of M1 macrophages ( Shen et al, 2016 ). MSC-EVs may also trigger the anti-inflammatory phenotype in hepatic macrophages through IGF-1 ( Fiore et al, 2020 ).…”

Section: Msc-evs and Immunomodulationmentioning

confidence: 99%

Extracellular Vesicle-Dependent Communication Between Mesenchymal Stromal Cells and Immune Effector Cells

Kamga

Tanasi

Krampera

2020

Front. Cell Dev. Biol.

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Mesenchymal stem/stromal cells (MSCs) are multipotent cells residing in the stromal tissues of the body and capable of promoting tissue repair and attenuating inflammatory processes through their immunomodulatory properties. Preclinical and clinical observations revealed that not only direct intercellular communication mediates MSC properties; in fact, a pivotal role is also played by the release of soluble and bioactive factors, such as cytokines, growth factor and extracellular vesicles (EVs). EVs are membrane-coated vesicles containing a large variety of bioactive molecules, including lipids, proteins, and nucleic acids, such as RNA. EVs release their contents into target cells, thus influencing cell fate through the control of intracellular processes. In addition, MSC-derived EVs can mediate modulatory effects toward different effector cells belonging to both innate and adaptive immunity. In this review, we will discuss the literature data concerning MSC-derived EVs, including the current standardized methods for their isolation and characterization, the mechanisms supporting their immunoregulatory properties, and their potential clinical application as alternative to MSC-based therapy for inflammatory reactions, such as graft-versus-host disease (GvHD).

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Human umbilical cord perivascular cells-derived extracellular vesicles mediate the transfer of IGF-I to the liver and ameliorate hepatic fibrogenesis in mice

Cited by 27 publications

References 35 publications

Extracellular Vesicles in Organ Fibrosis: Mechanisms, Therapies, and Diagnostics

Extracellular Vesicles in Organ Fibrosis: Mechanisms, Therapies, and Diagnostics

Molecular Pathways Modulated by Mesenchymal Stromal Cells and Their Extracellular Vesicles in Experimental Models of Liver Fibrosis

Extracellular Vesicle-Dependent Communication Between Mesenchymal Stromal Cells and Immune Effector Cells

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