Loading of metal isotope-containing intercalators for mass cytometry-based high-throughput quantitation of exosome uptake at the single-cell level

Wang, Jinheng; Tu, Chenggong; Zhang, Hui; Zhang, Jian; Feng, Yueyuan; Deng, Yangyang; Huo, Yongliang; Xie, Maobin; Yang, Bin; Zhou, Miao; Liu, Jinbao

doi:10.1016/j.biomaterials.2020.120152

Cited by 15 publications

(9 citation statements)

References 48 publications

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“…Since bilirubin significantly improves atherosclerosis which is closely associated with the immune response, it is likely that bilirubin also has an effect on the immune system. Thus, we used a high-throughput single cell technology, mass cytometry [ 31 , 35 ], to simultaneously measure the expression of 26 markers on immune cells from the spleen or peripheral blood at the single cell level. ViSNE analysis of CD45 + cells from the spleen was performed to visualize these high-dimensional mass cytometry data in two dimensions.…”

Section: Resultsmentioning

confidence: 99%

Bilirubin ameliorates murine atherosclerosis through inhibiting cholesterol synthesis and reshaping the immune system

et al. 2022

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Atherosclerosis is a chronic inflammatory disease caused mainly by lipid accumulation and excessive inflammatory immune response. Although the lipid-lowering and cardioprotective properties of bilirubin, as well as the negative relationship between bilirubin and atherosclerosis, were well documented, it is not yet clear whether bilirubin can attenuate atherosclerosis in vivo. In this study, we investigated the role of bilirubin in improving atherosclerosis. We found that mildly elevated bilirubin significantly reduced the risk factors of atherosclerosis, such as plasma glucose, total cholesterol, and low-density lipoprotein cholesterol, and the formation of atherosclerotic plaques, liver total cholesterol, and cholesterol ester concentration in apolipoprotein E-deficient (ApoE−/−) mice fed a western-type (high fat) diet. It was further found that bilirubin could promote the degradation of 3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMGCR), a rate-limiting enzyme for endogenous cholesterol synthesis. Using mass cytometry-based high dimensional single cell analysis, we observed a decrease of natural killer cells and an increase of dendritic cells and myeloid-derived suppressor cells, which all are closely associated with atherosclerosis risk factors and contribute to the improvement of atherosclerosis, in ApoE−/− mice treated with bilirubin. By in-depth analysis, modulation of multiple spleen or peripheral blood T cell clusters exhibiting either positive or negative correlations with total cholesterol or low-density lipoprotein cholesterol was detected after bilirubin treatment. In this study, we demonstrate that bilirubin serves as a negative regulator of atherosclerosis and reduces atherosclerosis by inhibiting cholesterol synthesis and modulating the immune system.

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Section: Resultsmentioning

confidence: 99%

Bilirubin ameliorates murine atherosclerosis through inhibiting cholesterol synthesis and reshaping the immune system

et al. 2022

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“…It enables EVs to fuse with the plasma membrane and release the contents directly into the cytoplasm membrane. In the microenvironment of cancerous tissues, the membrane fusion in response to acidic pH is considered to be a possible mechanism of content transfer 39 , 40 . At present, the mechanism of EVs uptake is still under further study, and there is no systematic study to explore whether the uptake of EVs by tumor cells is different from that of other normal cells.…”

Section: Tumor-derived Extracellular Vesiclesmentioning

confidence: 99%

Tumor-derived extracellular vesicles as messengers of natural products in cancer treatment

Xu¹,

Feng²,

Zhao³

et al. 2022

Theranostics

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Extracellular vesicles (EVs) are kinds of two-layer vesicles secreted by cells. They play significant roles in mediating component exchange between cells, signal transduction, and pathological development. Among them, the tumor-derived EVs (TDEVs) are found related to the tumor microenvironment and cancer development. TDEVs can be designed as a natural drug carrier with high tumor targeting and permeability. In recent years, drug delivery systems (DDS) based on TDEVs for cancer treatments have received considerable attention. In this review, the biological characteristics of TDEVs are introduced, especially the effect on the tumor. Furthermore, the various approaches to constructing DDS based on TDEVs are summarized. Then we listed examples of TDEVs successfully constructing treatment systems. The use of chemical drugs, biological drugs, and engineered drugs as encapsulated drugs are respectively introduced, particularly the application progress of active ingredients in traditional Chinese medicine. Finally, this article introduces the latest clinical research progress, especially the marketed preparations and challenges of clinical application of TDEVs.

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“…Recently, we reported the development of an engineering approach that involves loading of metal isotope‐containing intercalators into exosomes to quantify exosome uptake at the single‐cell level. [ 95 ] Exos can also be used to deliver small interfering RNAs (siRNAs) or pharmacologically active substances. [ 96 ] Excitingly, Exos are small and native in vivo, which can avoid phagocytosis, fuse with cell membranes, and bypass lysosomal phagocytosis.…”

Section: Exos As a Drug Carrier For Delivering Cargomentioning

confidence: 99%

Exosomes targeted towards applications in regenerative medicine

Xie

et al. 2021

Nano Select

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Exosomes are membrane‐bound nanovesicles containing complex cargoes including proteins, lipids, and nucleic acids (mRNAs and microRNAs), which can be derived from most cells. Increasing evidence has implicated exosomes as key players in intercellular and even interorganismal communications. Exosomes confer stability and can direct their cargoes to specific cell types for promoting cell growth and tissue regeneration. Exosome cargoes also appear to act in a combinatorial manner to communicate directives to other cells. This Review focuses on recent developments and findings of exosomes applied towards applications in tissue engineering and regenerative medicine, including healing of the skin, cardiovascular, skeletal, nervous, and visceral systems. The underlying mechanisms of action of exosomes in tissue regeneration are also discussed. In addition, we highlight examples whereby exosomes have been integrated with hydrogels for biofabrication and other related biomedical utilities such as drug delivery.

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Loading of metal isotope-containing intercalators for mass cytometry-based high-throughput quantitation of exosome uptake at the single-cell level

Cited by 15 publications

References 48 publications

Bilirubin ameliorates murine atherosclerosis through inhibiting cholesterol synthesis and reshaping the immune system

Bilirubin ameliorates murine atherosclerosis through inhibiting cholesterol synthesis and reshaping the immune system

Tumor-derived extracellular vesicles as messengers of natural products in cancer treatment

Exosomes targeted towards applications in regenerative medicine

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