Exosomes derived from TRAIL-engineered mesenchymal stem cells with effective anti-tumor activity in a mouse melanoma model

Shamili, Fazileh Hosseini; Bayegi, Houshang Rafatpanah; Salmasi, Zahra; Sadri, Kayvan; Mahmoudi, Mahmoud; Kalantari, Mahmoud Reza; Ramezani, Mohammad; Abnous, Khalil

doi:10.1016/j.ijpharm.2018.07.067

Cited by 59 publications

(49 citation statements)

References 58 publications

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“…MSCs have gained much interest in the therapy for various disorders and have also shown augmented protection in the treatment of neonatal hypoxic-ischemic brain injury [35]. Recently, exosomes derived from MSCs have been found to carry various kinds of mediators, miRNAs and proteins, which can mediate the function of MSCs [10,36,37]. Besides, the reports of altered expression of miRNAs in hypoxic-ischemic brain injury suggest that miRNAs may participate in the pathogenesis of this model [38].…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE:Bone mesenchymal stem cell-derived exosomal microRNA-29b-3p prevents hypoxic-ischemic injury in rat brain by activating the PTEN-mediated Akt signaling pathway

Hou¹,

Li²,

Zhao³

et al. 2020

J Neuroinflammation

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Background: Mesenchymal stem cells (MSCs) are suspected to exert neuroprotective effects in brain injury, in part through the secretion of extracellular vesicles like exosomes containing bioactive compounds. We now investigate the mechanism by which bone marrow MSCs (BMSCs)-derived exosomes harboring the small non-coding RNA miR-29b-3p protect against hypoxic-ischemic brain injury in rats. Methods:We established a rat model of middle cerebral artery occlusion (MCAO) and primary cortical neuron or brain microvascular endothelial cell (BMEC) models of oxygen and glucose deprivation (OGD). Exosomes were isolated from the culture medium of BMSCs. We treated the MCAO rats with BMSC-derived exosomes in vivo, and likewise the OGD-treated neurons and BMECs in vitro. We then measured apoptosis-and angiogenesis-related features using TUNEL and CD31 immunohistochemical staining and in vitro Matrigel angiogenesis assays. Results: The dual luciferase reporter gene assay showed that miR-29b-3p targeted the protein phosphatase and tensin homolog (PTEN). miR-29b-3p was downregulated and PTEN was upregulated in the brain of MCAO rats and in OGD-treated cultured neurons. MCAO rats and OGD-treated neurons showed promoted apoptosis and decreased angiogenesis, but overexpression of miR-29b-3p or silencing of PTEN could reverse these alterations. Furthermore, miR-29b-3p could negatively regulate PTEN and activate the Akt signaling pathway. BMSCs-derived exosomes also exerted protective effects against apoptosis of OGD neurons and cell apoptosis in the brain samples from MCAO rats, where we also observed promotion of angiogenesis.Conclusion: BMSC-derived exosomal miR-29b-3p ameliorates ischemic brain injury by promoting angiogenesis and suppressing neuronal apoptosis, a finding which may be of great significance in the treatment of hypoxic-ischemic brain injury.

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Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE:Bone mesenchymal stem cell-derived exosomal microRNA-29b-3p prevents hypoxic-ischemic injury in rat brain by activating the PTEN-mediated Akt signaling pathway

Hou¹,

Li²,

Zhao³

et al. 2020

J Neuroinflammation

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“…Isolation of TRAIL exosomes and application to tumor-bearing mice significantly reduced the tumor burden [ 49 ]. Exosomes derived from neonatal hUC-MSC have also emerged as potential therapeutic particles [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

Anti-Tumor Effects of Exosomes Derived from Drug-Incubated Permanently Growing Human MSC

Melzer

Ohe

Hass

2020

IJMS

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Similar to growth-limited human primary cultures of mesenchymal stroma/stem-like cells (MSC), the continuously proliferating human MSC544 cell line produced extracellular vesicles as characterized by expression of the tetraspanin molecules CD9, CD63, and CD81. Release of these particles was predominantly detectable during continuous cell growth of MSC544 in contrast to confluency-mediated transient growth arrest. For therapeutic use, these particles were isolated from proliferating MSC544 after taxol treatment and applied to different cancer cell cultures. A pronounced cytotoxicity of lung, ovarian, and breast cancer cells was observed primarily with taxol-loaded exosomes, similar to the effects displayed by application of taxol substance. While these findings suggested pronounced cancer cell targeting of MSC544 exosomes, a tumor therapeutic approach was performed using a mouse in vivo breast cancer model. Thus, intravenous injection of taxol-loaded MSC544 exosomes displayed superior tumor-reducing capabilities as compared to application of taxol exosomes by oral gavage. To broaden this therapeutic spectrum, epirubicin was applied to MSC544, and the derived exosomes likewise exhibited significant cytotoxic effects in different cancer cell cultures. These findings suggest an unlimited source for large-scale exosome production with reproducible quality to enable variable drug targeting of tumors or other diseases.

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“…Engineered EVs derived from MSCs have also shown cytotoxic effects on melanoma. Shamili and collaborators 83 engineered MSCs to overexpress TRAIL, a cytokine capable of inducing apoptosis particularly in tumor cells. Exosomes produced by these cells, when taken up by murine melanoma cells, induced cytotoxicity in vitro and in vivo 83 .…”

Section: Extracellular Vesicles and Anticancer Therapymentioning

confidence: 99%

“…Shamili and collaborators 83 engineered MSCs to overexpress TRAIL, a cytokine capable of inducing apoptosis particularly in tumor cells. Exosomes produced by these cells, when taken up by murine melanoma cells, induced cytotoxicity in vitro and in vivo 83 . Moreover, Muhsin‐Sharafaldine and colleagues showed that mice immunized with apoptotic bodies derived from B16F10 cells exogenously pulsed with ovalbumin inhibit tumor growth in vivo 84 .…”

Section: Extracellular Vesicles and Anticancer Therapymentioning

confidence: 99%

Extracellular vesicle-mediated crosstalk between melanoma and the immune system: Impact on tumor progression and therapy response

Pretti

Bernardes

Cruz

et al. 2020

Journal of Leukocyte Biology

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Melanoma is a very lethal tumor type that easily spreads and colonizes regional and distant tissues. Crucial phenotypic changes that favor melanoma metastasis are interposed by the tumor microenvironment (TME), representing a complex network in which malignant cells communicate not only with each other but also with stromal and immune cells. This cell-cell communication can be mediated by extracellular vesicles (EVs), which are lipid bilayer-delimited particles capable of carrying a wide variety of bioactive compounds. Both melanoma-derived or TME-derived EVs deliver important pro-and antitumor signals implicated in various stages of tumor progression, such as proliferation, metastasis, and treatment response. In this review, we highlight the recent advances in EV-mediated crosstalk between melanoma and immune cells and other important cells of the TME, and address different aspects of this bidirectional interaction as well as how this may hinder or trigger the development and progression of melanoma. We also discuss the potential of using EVs as biomarkers and therapeutic strategies for melanoma.

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Exosomes derived from TRAIL-engineered mesenchymal stem cells with effective anti-tumor activity in a mouse melanoma model

Cited by 59 publications

References 58 publications

RETRACTED ARTICLE:Bone mesenchymal stem cell-derived exosomal microRNA-29b-3p prevents hypoxic-ischemic injury in rat brain by activating the PTEN-mediated Akt signaling pathway

RETRACTED ARTICLE:Bone mesenchymal stem cell-derived exosomal microRNA-29b-3p prevents hypoxic-ischemic injury in rat brain by activating the PTEN-mediated Akt signaling pathway

Anti-Tumor Effects of Exosomes Derived from Drug-Incubated Permanently Growing Human MSC

Extracellular vesicle-mediated crosstalk between melanoma and the immune system: Impact on tumor progression and therapy response

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