Therapeutic and Diagnostic Translation of Extracellular Vesicles in Cardiovascular Diseases

Sahoo, Susmita; Adamiak, Marta; Mathiyalagan, Prabhu; Kenneweg, Franziska; Kafert-Kasting, Sabine; Thum, Thomas

doi:10.1161/circulationaha.120.049254

Cited by 147 publications

(127 citation statements)

References 185 publications

(167 reference statements)

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“…Despite this potential, EV diagnostics are still slowly being accepted by the public, regulatory agencies, and investors and, thus, to be integrated into long-term clinical strategies [218]. Several reviews and position papers in the literature have highlighted the open challenges that need to be faced to stimulate the EXO translational process to the clinic [6,[218][219][220][221][222][223]. Based on these papers, we feel that an agreement exists that standardization is the priority line of action.…”

Section: Discussion and Perspectivesmentioning

confidence: 99%

“…The above-mentioned characteristics make these microdevices perfectly suited for purifying exosomes for downstream analysis with the label-free characterization techniques discussed above. As can also be inferred from the excellent recent review by Sahoo and collaborators [222], the direct comparison between these devices and conventional isolation methods is not straightforward, because advantages and limitations depend on the specific device working principle. As a general comment, this approach for EXO isolation and enrichment is endowed with exceptional versatility, because custom devices can be designed for a wide range of specific purposes.…”

Section: Discussion and Perspectivesmentioning

confidence: 99%

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Recent Advances in the Label-Free Characterization of Exosomes for Cancer Liquid Biopsy: From Scattering and Spectroscopy to Nanoindentation and Nanodevices

et al. 2021

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Exosomes (EXOs) are nano-sized vesicles secreted by most cell types. They are abundant in bio-fluids and harbor specific molecular constituents from their parental cells. Due to these characteristics, EXOs have a great potential in cancer diagnostics for liquid biopsy and personalized medicine. Despite this unique potential, EXOs are not yet widely applied in clinical settings, with two main factors hindering their translational process in diagnostics. Firstly, conventional extraction methods are time-consuming, require large sample volumes and expensive equipment, and often do not provide high-purity samples. Secondly, characterization methods have some limitations, because they are often qualitative, need extensive labeling or complex sampling procedures that can induce artifacts. In this context, novel label-free approaches are rapidly emerging, and are holding potential to revolutionize EXO diagnostics. These methods include the use of nanodevices for EXO purification, and vibrational spectroscopies, scattering, and nanoindentation for characterization. In this progress report, we summarize recent key advances in label-free techniques for EXO purification and characterization. We point out that these methods contribute to reducing costs and processing times, provide complementary information compared to the conventional characterization techniques, and enhance flexibility, thus favoring the discovery of novel and unexplored EXO-based biomarkers. In this process, the impact of nanotechnology is systematically highlighted, showing how the effectiveness of these techniques can be enhanced using nanomaterials, such as plasmonic nanoparticles and nanostructured surfaces, which enable the exploitation of advanced physical phenomena occurring at the nanoscale level.

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Section: Discussion and Perspectivesmentioning

confidence: 99%

Section: Discussion and Perspectivesmentioning

confidence: 99%

Recent Advances in the Label-Free Characterization of Exosomes for Cancer Liquid Biopsy: From Scattering and Spectroscopy to Nanoindentation and Nanodevices

et al. 2021

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“…In addition, they are associated with tumorigenesis and tumor microenvironment [ 175 – 177 ]. Consequently, these unique functions and biology of the EVs in cell-to-cell communications through the delivery of cargo, including mRNAs, miRNAs, and lncRNAs, make them attractive as potential therapeutics and biomarkers in various diseases [ 178 , 179 ].…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNAs in brain tumors: roles and potential as therapeutic targets

et al. 2021

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Brain tumors are associated with adverse outcomes despite improvements in radiation therapy, chemotherapy, and photodynamic therapy. However, treatment approaches are evolving, and new biological phenomena are being explored to identify the appropriate treatment of brain tumors. Long non-coding RNAs (lncRNAs), a type of non-coding RNA longer than 200 nucleotides, regulate gene expression at the transcriptional, post-transcriptional, and epigenetic levels and are involved in a variety of biological functions. Recent studies on lncRNAs have revealed their aberrant expression in various cancers, with distinct expression patterns associated with their instrumental roles in cancer. Abnormal expression of lncRNAs has also been identified in brain tumors. Here, we review the potential roles of lncRNAs and their biological functions in the context of brain tumors. We also summarize the current understanding of the molecular mechanisms and signaling pathways related to lncRNAs that may guide clinical trials for brain tumor therapy.

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“…Further investigations into cEV origins, both cell and organ, will provide insight into biodistribution and interorgan communication to develop our understanding of systemic pathologies. Additionally, isolation of cEVs from models of cardiac pathologies will provide insights into disease mechanisms, allowing development of therapeutic strategies [49,108].…”

Section: Once Blood Has Clearedmentioning

confidence: 99%

Proteome characterisation of extracellular vesicles isolated from heart

et al. 2021

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Cardiac intercellular communication is critical for heart function and often dysregulated in cardiovascular diseases. While cardiac extracellular vesicles (cEVs) are emerging mediators of signalling, their isolation remains a technical challenge hindering our understanding of cEV protein composition. Here, we utilised Langendorffcollagenase-based enzymatic perfusion and differential centrifugation to isolate cEVs from mouse heart (yield 3-6 µg/heart). cEVs are ∼200 nm, express classical EV markers (Cd63/81/9 + , Tsg101 + , Pdcd6ip/Alix + ), and are depleted of blood (Alb/Fga/Hba) and cardiac damage markers (Mb, Tnnt2, Ldhb). Comparison with mechanically-derived EVs revealed greater detection of EV markers and decreased cardiac damage contaminants. Mass spectrometry-based proteomic profiling revealed 1721 proteins in cEVs, implicated in proteasomal and autophagic proteostasis, glycolysis, and fatty acid metabolism; essential functions often disrupted in cardiac pathologies. There was striking enrichment of 942 proteins in cEVs compared to mouse heart tissue -implicated in EV biogenesis, antioxidant activity, and lipid transport, suggesting active cargo selection and specialised function. Interestingly, cEVs contain marker proteins for cardiomyocytes, cardiac progenitors, B-cells, T-cells, macrophages, smooth muscle cells, endothelial cells, and cardiac fibroblasts, suggesting diverse cellular origin. We present a method of cEV isolation and provide insight into potential functions, enabling future studies into EV roles in cardiac physiology and disease.

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Therapeutic and Diagnostic Translation of Extracellular Vesicles in Cardiovascular Diseases

Cited by 147 publications

References 185 publications

Recent Advances in the Label-Free Characterization of Exosomes for Cancer Liquid Biopsy: From Scattering and Spectroscopy to Nanoindentation and Nanodevices

Recent Advances in the Label-Free Characterization of Exosomes for Cancer Liquid Biopsy: From Scattering and Spectroscopy to Nanoindentation and Nanodevices

Long non-coding RNAs in brain tumors: roles and potential as therapeutic targets

Proteome characterisation of extracellular vesicles isolated from heart

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