Exosomes derived from human bone marrow mesenchymal stem cells promote tumor growth in vivo

Zhu, Wei; Huang, Ling; Li, Yahong; Zhang, Xu; Gu, Jianmei; Yan, Yongmin; Xu, Xiaomeng; Wang, Mei; Qian, Hui; Xu, Wenrong

doi:10.1016/j.canlet.2011.10.002

Cited by 413 publications

(331 citation statements)

References 31 publications

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“…82 One study at 2013 reported that MSC-DEs due to enriched with miR-16, suppress tumor progression and angiogenesis via down-regulation of the expression of vascular endothelial growth factor (VEGF) in tumor cells 83 and another study at 2012 was reported that MSC-DEs promoted tumor growth in in vivo through the increasing VEGF expression by activating extracellular signal-regulated kinase1/2 (ERK1/2) pathway in tumor cells. 84 Xin et al showed that intravenous infusion of MSCderived exosomes after stroke improves neurogenesis, neurite remodeling and angiogenesis. 85 Exosomes have multimodal neuroprotective effects because they can pass over the blood-brain barrier in spite of most drugs.…”

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confidence: 99%

Mesenchymal Stem Cell-Derived Exosomes: New Opportunity in Cell-Free Therapy

2016

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confidence: 99%

Mesenchymal Stem Cell-Derived Exosomes: New Opportunity in Cell-Free Therapy

2016

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“…hucMSC-Ex was prepared and purified as described previously. 22 Nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) analyses confirmed spheroid morphology of hucMSC-Ex (diameter 30-100 nm; Figures S2A and S2B). Western blot results confirmed expression of exosomal markers CD9, CD61, and CD63 in hucMSC-Ex ( Figure S2C).…”

Section: Hucmsc-ex Rescued CCL 4 -Induced Liver Failurementioning

confidence: 76%

“…22 Briefly, bovine exosomes and protein aggregates in DMEM/10% FBS were removed by ultracentrifugation at 100,000 Â g for 16 hr at 4 C. hucMSCs and HFL-1-conditional medium (MSC-CM and HFL-CM) were collected after 48 hr culture and centrifuged for 20 min at 2,000 Â g to remove cell debris. Then supernatant was transferred to an ultracentrifuge tube underlain with 30% sucrose/ D 2 O cushion (density 1.210 g/cm 3 ), followed by ultracentrifugation at 100,000 Â g for 1 hr at 4 C. Exosomes were collected from the bottom of the tube and concentrated using 100 KDa molecular weight cutoff ultrafiltration membrane (MWCO) (Millipore) at 1,000 Â g for 30 min.…”

Section: Isolation and Characterization Of Exosomesmentioning

confidence: 99%

hucMSC Exosome-Derived GPX1 Is Required for the Recovery of Hepatic Oxidant Injury

et al. 2017

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Exosomes are small biological membrane vesicles secreted by various cells, including mesenchymal stem cells (MSCs). We previously reported that MSC-derived exosomes (MSC-Ex) can elicit hepatoprotective effects against toxicant-induced injury. However, the success of MSC-Ex-based therapy for treatment of liver diseases and the underlying mechanisms have not been well characterized. We used human umbilical cord MSC-derived exosome (hucMSC-Ex) administrated by tail vein or oral gavage at different doses and, in engrafted liver mouse models, noted antioxidant and anti-apoptotic effects and rescue from liver failure. A single systemic administration of hucMSC-Ex (16 mg/kg) effectively rescued the recipient mice from carbon tetrachloride (CCl 4 )-induced liver failure. Moreover, hucMSC-Ex-derived glutathione peroxidase1 (GPX1), which detoxifies CCl 4 and H 2 O 2 , reduced oxidative stress and apoptosis. Knockdown of GPX1 in hucMSCs abrogated antioxidant and anti-apoptotic abilities of hucMSC-Ex and diminished the hepatoprotective effects of hucMSC-Ex in vitro and in vivo. Thus, hucMSC-Ex promote the recovery of hepatic oxidant injury through the delivery of GPX1.

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“…However, it is also shown that MSC-derived EVs stimulate tumor vascularization and tumor growth, which might induce undesirable off-target effects [180]. Besides MSCs, immature DCs have also been proposed as an interesting EV source due to their low immunogenicity, immunosuppressive effects and the ease with which autologous sources can be obtained [109,181].…”

Section: (Nct02138331)mentioning

confidence: 99%

Therapeutic and diagnostic applications of extracellular vesicles

Stremersch

Smedt

Raemdonck

2016

Journal of Controlled Release

157

103

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During the past two decades, extracellular vesicles (EVs) have been identified as important mediators of intercellular communication, enabling the functional transfer of bioactive molecules from one cell to another. Consequently, it is becoming increasingly clear that these vesicles are involved in many (patho)physiological processes, providing opportunities for therapeutic applications. Moreover, it is known that the molecular composition of EVs reflects the physiological status of the producing cell and tissue, rationalizing their exploitation as biomarkers in various diseases. In this review the composition, biogenesis and diversity of EVs is discussed in a therapeutic and diagnostic context. We describe emerging therapeutic applications, including the use of EVs as drug delivery vehicles and as cell-free vaccines, and reflect on future challenges for clinical translation. Finally, we discuss the use of EVs as a biomarker source and highlight recent studies and clinical successes.

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Exosomes derived from human bone marrow mesenchymal stem cells promote tumor growth in vivo

Cited by 413 publications

References 31 publications

Mesenchymal Stem Cell-Derived Exosomes: New Opportunity in Cell-Free Therapy

Mesenchymal Stem Cell-Derived Exosomes: New Opportunity in Cell-Free Therapy

hucMSC Exosome-Derived GPX1 Is Required for the Recovery of Hepatic Oxidant Injury

Therapeutic and diagnostic applications of extracellular vesicles

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