Mesenchymal stem cell and derived exosome as small RNA carrier and Immunomodulator to improve islet transplantation

Wen, Di; Peng, Yang; Liu, Di; Weizmann, Yossi; Mahato, Ram I.

doi:10.1016/j.jconrel.2016.07.044

Cited by 140 publications

(114 citation statements)

References 50 publications

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“…One underlying mechanism could be that SC-EVs inhibit T cell differentiation into Th1 cells (98) or Th2 cells (52) ( Table 1) while promoting Treg differentiation (91) ( Table 1) by inducing phenotypic transformation of APCs (52,77,91,(97)(98)(99). Another underlying mechanism could be that SC-EVs regulate the expression of the related genes involved in inflammation and immune cell development; for example, they could upregulate miR-let-7b and miR-let-7d and downregulate miR-155 in Treg cells (119). Additionally, the study on MSC transplantation (MSCT) in tight-skin mice model demonstrated that BM-MSCs in recipients could take up and reuse miR-151-5p loaded in the MSC-EVs of donors to inhibit IL4Rα/mTOR pathway, downregulate IL-4, inhibit Th2 cell differentiation and infiltration, and contribute to the rebuilding of BM-MSC function and BM homeostasis (78) ( Table 1).…”

Section: Stem Cell-derived Extracellular Vesicles Inhibit Naive T Celmentioning

confidence: 99%

Immunoregulatory Effects of Stem Cell-Derived Extracellular Vesicles on Immune Cells

Xie

Wang²,

She

et al. 2020

Front. Immunol.

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Recent investigations on the regulatory action of extracellular vesicles (EVs) on immune cells in vitro and in vivo have sparked interest on the subject. As commonly known, EVs are subcellular components secreted by a paracellular mechanism and are essentially a group of nanoparticles containing exosomes, microvesicles, and apoptotic bodies. They are double-layer membrane-bound vesicles enriched with proteins, nucleic acids, and other active compounds. EVs are recognized as a novel apparatus for intercellular communication that acts through delivery of signal molecules. EVs are secreted by almost all cell types, including stem/progenitor cells. The EVs derived from stem/progenitor cells are analogous to the parental cells and inhibit or enhance immune response. This review aims to provide its readers a comprehensive overview of the possible mechanisms underlying the immunomodulatory effects exerted by stem/progenitor cell-derived EVs upon natural killer (NK) cells, dendritic cells (DCs), monocytes/macrophages, microglia, T cells, and B cells.

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Section: Stem Cell-derived Extracellular Vesicles Inhibit Naive T Celmentioning

confidence: 99%

Immunoregulatory Effects of Stem Cell-Derived Extracellular Vesicles on Immune Cells

Xie

Wang²,

She

et al. 2020

Front. Immunol.

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“…4 Studies have shown that MSCs can achieve a therapeutic effect in vivo via paracrine action 5, 6 and direct differentiation. Subsequent studies indicated that MSC-secreted extracellular vesicles (EVs), including microvesicles (MVs; 0.1–1 mm in diameter) and exosomes (40–100 nm in diameter), 7, 8 may contribute to the therapeutic potency of MSCs by mediating cell–cell micro-communication and transporting paracrine factors during angiogenesis, tissue regeneration and immune regulation. 9, 10, 11, 12 …”

Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cell-derived exosomes as a new therapeutic strategy for liver diseases

et al. 2017

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The administration of mesenchymal stem cells (MSCs) as a therapy for liver disease holds great promise. MSCs can differentiate into hepatocytes, reduce liver inflammation, promote hepatic regeneration and secrete protective cytokines. However, the risks of iatrogenic tumor formation, cellular rejection and infusional toxicity in MSC transplantation remain unresolved. Accumulating evidence now suggests that a novel cell-free therapy, MSC-secreted exosomes, might constitute a compelling alternative because of their advantages over the corresponding MSCs. They are smaller and less complex than their parent cells and, thus, easier to produce and store, they are devoid of viable cells, and they present no risk of tumor formation. Moreover, they are less immunogenic than their parent cells because of their lower content in membrane-bound proteins. This paper reviews the biogenesis of MSC exosomes and their physiological functions, and highlights the specific biochemical potential of MSC-derived exosomes in restoring tissue homeostasis. In addition, we summarize the recent advances in the role of exosomes in MSC therapy for various liver diseases, including liver fibrosis, acute liver injury and hepatocellular carcinoma. This paper also discusses the potential challenges and strategies in the use of exosome-based therapies for liver disease in the future.

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“…In a recent study, endothelial progenitor cell-derived exosomes containing abundant miRNA-126-3p and 5p could attenuate organ injury and vascular permeability in cecal ligation and puncture (CLP)-induced sepsis [103]. In another study, Wen et al utilized human bone marrow mesenchymal stem cells (hBMSCs) and their exosomes (which are rich in siFas and anti-miRNA-375) to restrain islet apoptosis and primary nonfunction (PNF) during islet transplantation in humanized NOD scid gamma (NSG) mice [104]. However, the large-scale production of exosomes is not easily available due to cost.…”

Section: Cell-derived Membrane Vesiclesmentioning

confidence: 99%

Recent progress in microRNA-based delivery systems for the treatment of human disease

Chen

Huang

2019

ExRNA

132

118

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MicroRNAs (miRNAs) are naturally occurring, small non-coding RNAs that mediate posttranscriptional regulation. Based on the level of sequence complementarity, miRNAs lead to the degradation of target mRNAs or the suppression of mRNA translation, thereby inhibiting the synthesis of proteins and achieving the regulation of genes. miRNAs, which exhibit tissue-and temporal-specific expression, are important negative regulatory RNAs that decrease the levels of other functional genes. miRNAs play a crucial role in disease progression and prognosis and thus exhibit potential for developing novel therapeutics. Due to the instability of miRNAs and their complex environment, including degradation by nucleases in vivo, the safety and effectiveness of miRNA delivery has become the focus of recent attention. Therefore, we discuss some representative advances related to the application of viral-and nonviral-mediated miRNA delivery systems and provide a new perspective on the future of miRNA-based therapeutic strategies.

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Mesenchymal stem cell and derived exosome as small RNA carrier and Immunomodulator to improve islet transplantation

Cited by 140 publications

References 50 publications

Immunoregulatory Effects of Stem Cell-Derived Extracellular Vesicles on Immune Cells

Immunoregulatory Effects of Stem Cell-Derived Extracellular Vesicles on Immune Cells

Mesenchymal stem cell-derived exosomes as a new therapeutic strategy for liver diseases

Recent progress in microRNA-based delivery systems for the treatment of human disease

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