Mesenchymal stromal/stem cell-derived extracellular vesicles in tissue repair: challenges and opportunities

Varderidou-Minasian, Suzy; Lorenowicz, Magdalena J.

doi:10.7150/thno.40122

Cited by 160 publications

(150 citation statements)

References 174 publications

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“…Recently, the role of EVs in tissue repair and regeneration has been extensively studied. In particular, MSC-derived EVs have shown a pro-regenerative effect in several tissues, including heart, lung, bone, skin, brain, kidney, and liver (Fiore et al, 2018;Varderidou-Minasian and Lorenowicz, 2020). As reported for MSCs, also MSC-EVs exhibit therapeutic effects in several preclinical models of hepatic fibrosis ( Table 2).…”

Section: Msc-ev Effects In Liver Fibrosismentioning

confidence: 64%

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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Section: Msc-ev Effects In Liver Fibrosismentioning

confidence: 64%

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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“…MSCs may exert their effects via paracrine mechanisms involving soluble factors [ 72 , 73 ], or via extracellular vesicles [ 74 ]. Therefore, conditioned media (HGM, MCD, or C16:0) were collected separately from HCs, MSCs, and co-cultures of both after 48 h of culture.…”

Section: Resultsmentioning

confidence: 99%

Mitochondrial Transfer by Human Mesenchymal Stromal Cells Ameliorates Hepatocyte Lipid Load in a Mouse Model of NASH

et al. 2020

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Mesenchymal stromal cell (MSC) transplantation ameliorated hepatic lipid load; tissue inflammation; and fibrosis in rodent animal models of non-alcoholic steatohepatitis (NASH) by as yet largely unknown mechanism(s). In a mouse model of NASH; we transplanted bone marrow-derived MSCs into the livers; which were analyzed one week thereafter. Combined metabolomic and proteomic data were applied to weighted gene correlation network analysis (WGCNA) and subsequent identification of key drivers. Livers were analyzed histologically and biochemically. The mechanisms of MSC action on hepatocyte lipid accumulation were studied in co-cultures of hepatocytes and MSCs by quantitative image analysis and immunocytochemistry. WGCNA and key driver analysis revealed that NASH caused the impairment of central carbon; amino acid; and lipid metabolism associated with mitochondrial and peroxisomal dysfunction; which was reversed by MSC treatment. MSC improved hepatic lipid metabolism and tissue homeostasis. In co-cultures of hepatocytes and MSCs; the decrease of lipid load was associated with the transfer of mitochondria from the MSCs to the hepatocytes via tunneling nanotubes (TNTs). Hence; MSCs may ameliorate lipid load and tissue perturbance by the donation of mitochondria to the hepatocytes. Thereby; they may provide oxidative capacity for lipid breakdown and thus promote recovery from NASH-induced metabolic impairment and tissue injury.

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“…8 MSC-derived extracellular vesicles (EVs) are membranous structures loaded with proteins, lipids, carbohydrates and nucleic acids, which play an important role in cellcell communication and advances tissue repair. 9 The abilities of stem cell-secreted EVs to shape tumour microenvironment, regulate immunomodulation and stimulate endogenous repair processes during tissue damage have been investigated. 10 Moreover, EVs derived from human umbilical cord-blood MSCs have been reported to accelerate human skin regeneration.…”

Section: Introductionmentioning

confidence: 99%

Extracellular vesicle‐carried microRNA‐27b derived from mesenchymal stem cells accelerates cutaneous wound healing via E3 ubiquitin ligase ITCH

Cheng

Chen

et al. 2020

J Cellular Molecular Medi

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Mesenchymal stromal/stem cell-derived extracellular vesicles in tissue repair: challenges and opportunities

Cited by 160 publications

References 174 publications

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

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

Mitochondrial Transfer by Human Mesenchymal Stromal Cells Ameliorates Hepatocyte Lipid Load in a Mouse Model of NASH

Extracellular vesicle‐carried microRNA‐27b derived from mesenchymal stem cells accelerates cutaneous wound healing via E3 ubiquitin ligase ITCH

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