Exosomes Transfer Among Different Species Cells and Mediating miRNAs Delivery

Zhou, Yueyuan; Tian, Tian; Zhu, Ye; Ali, Doulathunnisa Jaffar; Hu, Feihu; Qi, Yuhua; Sun, Bo; Zhang, Xiao

doi:10.1002/jcb.26077

Cited by 39 publications

(22 citation statements)

References 41 publications

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“…We could not detect CpG island on the promoter of these three miRNAs, indicating that these may not be directly targeted by Tet1 and Tet2. MSCs can secrete a large number of exosomes 32 , which can transfer proteins, mRNAs, and miRNAs to mediate physiological and pathological processes 19 , 33 , 34 . We therefore sought to test whether exosome secretion is involved in miRNA accumulation in Tet DKO BMMSCs.…”

Section: Resultsmentioning

confidence: 99%

Tet1 and Tet2 maintain mesenchymal stem cell homeostasis via demethylation of the P2rX7 promoter

et al. 2018

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Ten-eleven translocation (Tet) family-mediated DNA oxidation represents an epigenetic modification capable of converting 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC), which regulates various biological processes. However, it is unknown whether Tet family affects mesenchymal stem cells (MSCs) or the skeletal system. Here we show that depletion of Tet1 and Tet2 results in impaired self-renewal and differentiation of bone marrow MSCs (BMMSCs) and a significant osteopenia phenotype. Tet1 and Tet2 deficiency reduces demethylation of the P2rX7 promoter and downregulates exosome release, leading to intracellular accumulation of miR-297a-5p, miR-297b-5p, and miR-297c-5p. These miRNAs inhibit Runx2 signaling to impair BMMSC function. We show that overexpression of P2rX7 rescues the impaired BMMSCs and osteoporotic phenotype in Tet1 and Tet2 double knockout mice. These results indicate that Tet1 and Tet2 play a critical role in maintaining BMMSC and bone homeostasis through demethylation of P2rX7 to control exosome and miRNA release. This Tet/P2rX7/Runx2 cascade may serve as a target for the development of novel therapies for osteopenia disorders.

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Section: Resultsmentioning

confidence: 99%

Tet1 and Tet2 maintain mesenchymal stem cell homeostasis via demethylation of the P2rX7 promoter

et al. 2018

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“…Exosomes deliver their surface protein and cytoplasm to the recipient cell by fusing with the target-cell membrane at which point they open up. Many studies show that exosomes enter cells, release their cargo and mediate many physiological and pathological processes [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Recent advancements in the use of exosomes as drug delivery systems

et al. 2018

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Extracellular vesicles (EVs) are the substances that are released by most types of cells and have an important role in cell to cell communication. Among the most highly researched EVs are exosome. Recent studies show that exosomes derived from cells have different roles and targets. Many studies show that exosome can efficiently deliver many different kinds of cargo to the target cell. Therefore, they are often used to deliver therapeutic cargo for treatment. The exosomes that have been used include both natural ones and those that have been modified with other substances to increase the delivery ability. This article provides a review of both exosomes derived from various cells and modified exosome and their ability in delivering the many kinds of cargo to the target cell.

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“…The culture media of C9HuH-7, LC9-293 and HN3LC9-293 cells were collected and the exosomes were isolated as previously described (Zhou et al, 2017). Total protein was isolated from 20 µL of exosomes using RIPA buffer (Beyotime Biotechnology, China) and quantified using Micro BCA protein assay kit (CoWin Biotechnology, China) as per the manufacturer's protocol.…”

Section: Isolation Of Exosomesmentioning

confidence: 99%

Engineering of HN3 increases the tumor targeting specificity of exosomes and upgrade the anti-tumor effect of sorafenib on HuH-7 cells

Ali

et al. 2020

PeerJ

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Safe, efficient and cancer cell targeted delivery of CRISPR/Cas9 is important to increase the effectiveness of available cancer treatments. Although cancer derived exosomes offer significant advantages, the fact that it carries cancer related/inducing signaling molecules impedes them from being used as a reliable drug delivery vehicle. In this study, we report that normal epithelial cell-derived exosomes engineered to have HN3 (HN3LC9-293exo), target tumor cells as efficiently as that of the cancer cell-derived exosomes (C9HuH-7exo). HN3LC9-293exo were quickly absorbed by the recipient cancer cell in vitro. Anchoring HN3 to the membrane of the exosomes using LAMP2, made HN3LC9-293exo to specifically enter the GPC3+ HuH-7 cancer cells than the GPC3− LO2 cells in a co-culture model. Further, sgIQ 1.1 plasmids were loaded to exosomes and surprisingly, in combination with sorafenib, synergistic anti-proliferative and apoptotic effect of loaded HN3LC9-293exo was more than the loaded C9HuH-7exo. While cancer-derived exosomes might induce the drug resistance and tumor progression, normal HEK-293 cells-derived exosomes with modifications for precise cancer cell targeting like HN3LC9-293exo can act as better, safe and natural delivery systems to improve the efficacy of the cancer treatments.

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Exosomes Transfer Among Different Species Cells and Mediating miRNAs Delivery

Cited by 39 publications

References 41 publications

Tet1 and Tet2 maintain mesenchymal stem cell homeostasis via demethylation of the P2rX7 promoter

Tet1 and Tet2 maintain mesenchymal stem cell homeostasis via demethylation of the P2rX7 promoter

Recent advancements in the use of exosomes as drug delivery systems

Engineering of HN3 increases the tumor targeting specificity of exosomes and upgrade the anti-tumor effect of sorafenib on HuH-7 cells

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