Adipose-derived stem cell extracellular vesicles: A systematic review✰

Wong, Daniel; Banyard, Derek A.; Santos, Pauline Joy F; Sayadi, Lohrasb; Evans, Gregory R. D.; Widgerow, Alan D.

doi:10.1016/j.bjps.2019.03.008

Cited by 35 publications

(24 citation statements)

References 67 publications

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“…In recent years, it has been brought to the fore, which is mainly due to the remarkable advancement of the identi cation of EVs and related mechanisms have been continuously explored [21]. In particular, hADSC-sEVs have shown great potential in a variety of disease models [22][23][24][25].…”

Section: Discussionmentioning

confidence: 99%

Small Extracellular Vesicles From Human Adipose-derived Stem Cells: A Potential Promoter of Keeping Fat Graft Survival

Chen

Tang

et al. 2020

Preprint

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Background: Small extracellular vesicles (sEVs) with genetic information secreted by cells play a crucial role in the cellular microenvironment. In this study, our purpose is to explore the characteristics of the small extracellular vesicles of human adipose-derived stem cells (hADSC-sEVs) and studied the role of hADSC-sEVs in improving the survival rate of grafted fat.Methods: In the present study, we used the transmission electron microscopy, nano-tracking analysis, nanoflow surface protein analysis, zeta potential value to identify sEVs. SEVs' trajectory was traced dynamically to verify whether hADSC-sEVs can be internalized into human umbilical vein endothelial cells (HUVECs) in vitro. The angiogenic property of hADSC-sEVs was observed by measuring the volume, weight and histological analysis of the grafted fats in nude mice modles. Results: Our research showed that the extracellular vesicles were sEVs with double-layer membrane structure and the diameter of which is within 30-150nm. hADSC-sEVs exert biological influence mainly through internalization into cells. Compared with the control group, the hADSC-sEVs group had a significantly higher survival rate of grafted fat, morphological integrity and a lower degree of inflammation and fibrosis. And immunohistochemistry showed that hADSC-sEVs significantly increased the neovascularisation and the expression of CD34, VEGFR2 and KI-67 in the graft tissue. Conclusions: As a potential nanomaterial, hADSC-sEVs has been explored in the field of cell-free application of stem cell technology. hADSC-sEVs promoted the survival of grafted fats by promoting the formation of new blood vessels, which is another promising progress in the field of regenerative medicine. We believe that hADSC-sEVs will have a broad application prospect in the field of regenerative medicine in the future.

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Section: Discussionmentioning

confidence: 99%

Small Extracellular Vesicles From Human Adipose-derived Stem Cells: A Potential Promoter of Keeping Fat Graft Survival

Chen

Tang

et al. 2020

Preprint

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“…The adherent cells were cultured for 7-14 days until the cells reached 80-90% con uence. The cells were then digested with 0.25% trypsin plus 0.02% EDTA (Invitrogen) and sub- vesicles from normoxic ADSC medium or hypoxic medium followed the multistep ultracentrifugation process as previously reported [31]. Brie y, the conditioned medium containing extracellular vesicles was obtained by centrifugation at 2000 × g for 10 min and 10,000 × g for 30 min at 4 °C to remove dead cells and cell debris, followed by ltering with a sterilized lter (0.22 μm, Millipore).…”

Section: Cell Harvestmentioning

confidence: 99%

Hypoxic ADSCs-derived EVs Promote the Proliferation and Chondrogenic Differentiation of Cartilage Stem/progenitor Cells

Xue

Jiang²,

Zhang³

et al. 2020

Preprint

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Background： Cartilage tissue engineering is a promising option for repairing cartilage defects caused by trauma, inflammation and osteoarthritis, although harvesting a large number of seeding cells with stable phenotypes remains a major challenge. Cartilage stem/progenitor cells (CSPCs) seem to be a promising cell source. Hypoxic extracellular vesicles secreted by mesenchymal stem cells may play a major role in cell-cell and tissue-tissue communication by transporting various RNAs and proteins in mesenchymal stem cell-based therapy. In the current study, we aimed to evaluate the effect of hypoxic adipose-derived stem cells (ADSCs)-derived extracellular vesicles (EVs) on CSPCs proliferation and differentiation. Methods: The characteristics of ADSCs-derived EVs were identified by and flow cytometric analysis. Proliferation, migration, and cartilage-related gene expression of CSPCs were measured with or without the presence of hypoxic ADSCs-derived EVs. The effect of ADSC-derived EVs on CSPCs were evaluated in alginate hydrogel culture, and SEM, histological staining, biochemical and biomechanical analysis were performed to evaluate the effect of hypoxic ADSCs-derived EVs on CSPCs in alginate hydrogel culture. Results: The results indicated that the majority of ADSC-derived EVs exhibited a round-shaped or cup-shaped morphology with a diameter of 40–1000 nm and expressed CD9, CD63, and CD81. CSPCs migration and proliferation were enhanced by hypoxic ADSCs-derived EVs, which also increased the expression of cartilage-related genes. The hypoxic ADSCs-derived EVs induced CSPCs to produce significantly more cartilage matrix and proteoglycan. Conclusions: The present study indicated that hypoxic ADSCs-derived EVs improved the proliferation and chondrogenic differentiation of CSPCs for cartilage tissue engineering.

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“…Numerous studies using EVs from mouse or human cells have isolated cell lines for loading and delivering drugs, including EL-4 (mouse lymphoma cell line), RAW264.7 (mouse macrophage cell line) [ 16 ], LNCaP and PC-3 (prostate cancer cell lines) [ 17 ], and U937 cells (monocyte cell line) [ 18 ], as well as other MSCs (human bone marrow-derived mesenchymal stem cell lines) [ 19 ]. However, studies that isolate and characterize drug loading and delivery in primary human ADSCs are very few in number [ 20 ]. Herein, we reported a methodical approach for the isolation, enrichment, and characterization of EVs from primary human ADSC-derived EVs for use in drug delivery nano-transporters.…”

Section: Introductionmentioning

confidence: 99%

Extracellular Vesicles Act as Nano-Transporters of Tyrosine Kinase Inhibitors to Revert Iodine Avidity in Thyroid Cancer

et al. 2021

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A new approach for using extracellular vesicles (EVs) to deliver tyrosine kinase inhibitors (TKIs) to enhance iodine avidity in radioactive iodine-refractory thyroid cancer is needed. We isolated and characterized primary human adipose-derived stem cells (ADSCs) and isolated their EVs. The EVs were characterized by transmission electron microscopy, nanoparticle tracking analysis, and western blotting. A new TKI was loaded into the EVs by incubation (37 °C; 10 min) or sonication (18 cycles; 4 s per cycle) with 2 s intervals and a 2 min ice bath every six cycles. TKI loading was confirmed and measured by mass spectrometry. EV uptake into radioactive iodine-refractory thyroid cancer cells (SW1736 cells) was confirmed by microscopy. We treated the SW1736 cells with vehicle, TKI, or TKI-loaded EVs (sonication TKI-loaded EVs [EVsTKI(S)]) and examined the expression of iodide-metabolizing proteins and radioiodine uptake in the SW1736 cells. ADSCs cells showed >99% of typical stem cell markers, such as CD90 and CD105. The EVs displayed a round morphology, had an average size of 211.4 ± 3.83 nm, and were positive for CD81 and Alix and negative for cytochrome c. The mass spectrometry results indicate that the sonication method loaded ~4 times more of the TKI than did the incubation method. The EVsTKI(S) were used for further experiments. Higher expression levels of iodide-metabolizing mRNA and proteins in the EVsTKI(S)-treated SW1736 cells than in TKI-treated SW1736 cells were confirmed. EVsTKI(S) treatment enhanced 125I uptake in the recipient SW1736 cells compared with free-TKI treatment. This is the first study that demonstrated successful delivery of a TKI to radioactive iodine-refractory thyroid cancer cells using EVs as the delivery vehicle. This approach can revert radioiodine-resistant thyroid cancer cells back to radioiodine-sensitive thyroid cancer cells.

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Adipose-derived stem cell extracellular vesicles: A systematic review✰

Cited by 35 publications

References 67 publications

Small Extracellular Vesicles From Human Adipose-derived Stem Cells: A Potential Promoter of Keeping Fat Graft Survival

Small Extracellular Vesicles From Human Adipose-derived Stem Cells: A Potential Promoter of Keeping Fat Graft Survival

Hypoxic ADSCs-derived EVs Promote the Proliferation and Chondrogenic Differentiation of Cartilage Stem/progenitor Cells

Extracellular Vesicles Act as Nano-Transporters of Tyrosine Kinase Inhibitors to Revert Iodine Avidity in Thyroid Cancer

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Adipose-derived stem cell extracellular vesicles: A systematic review✰

Cited by 35 publications

References 67 publications

Small Extracellular Vesicles From Human Adipose-derived Stem Cells: A Potential Promoter of Keeping Fat Graft Survival

Small Extracellular Vesicles From Human Adipose-derived Stem Cells: A Potential Promoter of Keeping Fat Graft Survival

Hypoxic ADSCs-derived EVs&nbsp;Promote the Proliferation and Chondrogenic Differentiation of Cartilage Stem/progenitor Cells

Extracellular Vesicles Act as Nano-Transporters of Tyrosine Kinase Inhibitors to Revert Iodine Avidity in Thyroid Cancer

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Hypoxic ADSCs-derived EVs Promote the Proliferation and Chondrogenic Differentiation of Cartilage Stem/progenitor Cells