Tracking tools of extracellular vesicles for biomedical research

Liu, Qisong; Huang, Jianghong; Xia, Jiang; Liang, Yujie; Li, Guangheng

doi:10.3389/fbioe.2022.943712

Cited by 17 publications

(14 citation statements)

References 104 publications

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“…Even specific exosomes hide numerous problems due to the wrapping of various complex molecules, including the uncontrollability of the effects produced by unknown molecules and the quantification of miRNA, lncRNA, and circRNA in MSC-Exos [ 168 ]. In addition, there is still a lack of pharmacokinetics and biodistribution of exosomes in vivo [ 169 , 170 ]. Undeniably, several organizations, including the International Society for Extracellular Vesicles, are try to develop guidelines for MSC-Exos for the treatment of OA [ 171 ].…”

Section: Conclusion and Prospectsmentioning

confidence: 99%

Enhancement of the therapeutic efficacy of mesenchymal stem cell-derived exosomes in osteoarthritis

Zhang,

Zhao,

Sun

et al. 2023

Cell Mol Biol Lett

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Osteoarthritis (OA), a common joint disorder with articular cartilage degradation as the main pathological change, is the major source of pain and disability worldwide. Despite current treatments, the overall treatment outcome is unsatisfactory. Thus, patients with severe OA often require joint replacement surgery. In recent years, mesenchymal stem cells (MSCs) have emerged as a promising therapeutic option for preclinical and clinical palliation of OA. MSC-derived exosomes (MSC-Exos) carrying bioactive molecules of the parental cells, including non-coding RNAs (ncRNAs) and proteins, have demonstrated a significant impact on the modulation of various physiological behaviors of cells in the joint cavity, making them promising candidates for cell-free therapy for OA. This review provides a comprehensive overview of the biosynthesis and composition of MSC-Exos and their mechanisms of action in OA. We also discussed the potential of MSC-Exos as a therapeutic tool for modulating intercellular communication in OA. Additionally, we explored bioengineering approaches to enhance MSC-Exos’ therapeutic potential, which may help to overcome challenges and achieve clinically meaningful OA therapies.

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Section: Conclusion and Prospectsmentioning

confidence: 99%

Enhancement of the therapeutic efficacy of mesenchymal stem cell-derived exosomes in osteoarthritis

Zhang,

Zhao,

Sun

et al. 2023

Cell Mol Biol Lett

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“…One possibility is to use naturally derived particles with lipid membranes to deliver therapeutics across the BBB. Extracellular vesicles (EVs) are small particles naturally released from cells that carry and deliver bioactive molecules as a method of cell-to-cell communication, and EVs from various types of cells have been shown to target tumors and cross the BBB 12,13 . EVs can be classified by mechanism of biogenesis, size, function, or composition; examples of EVs classified by biogenesis include exosomes, microvesicles, and apoptotic bodies 14 .…”

Section: Introductionmentioning

confidence: 99%

Magnetic particle imaging reveals that iron-labeled extracellular vesicles accumulate in brains of mice with metastases

Toomajian,

Tundo,

Ural

et al. 2024

Preprint

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The incidence of breast cancer remains high worldwide and is associated with a significant risk of metastasis to the brain that can be fatal; this is due, in part, to the inability of therapeutics to cross the blood brain barrier (BBB). Extracellular vesicles (EVs) have been found to cross the BBB and further, have been used to deliver drugs to tumors. EVs from different cell types appear to have different patterns of accumulation and retention as well as efficiency of bioactive cargo delivery to recipient cells in the body. Engineering EVs as delivery tools to treat brain metastases, therefore, will require an understanding of the timing of EV accumulation, and their localization relative to metastatic sites. Magnetic particle imaging (MPI) is a sensitive and quantitative imaging method that directly detects superparamagnetic iron. Here, we demonstrate MPI as a novel tool to characterize EV biodistribution in metastatic disease after labeling EVs with superparamagnetic iron oxide (SPIO) nanoparticles. Iron-labeled EVs (FeEVs) were collected from iron-labeled parental primary 4T1 tumor cells and brain-seeking 4T1BR5 cells, followed by injection into mice with orthotopic tumors or brain metastases. MPI quantification revealed that FeEVs were retained for longer in orthotopic mammary carcinomas compared to SPIOs. MPI signal due to iron could only be detected in brains of mice bearing brain metastases after injection of FeEVs, but not SPIOs, or FeEVs when mice did not have brain metastases. These findings indicate the potential use of EVs as a therapeutic delivery tool in primary and metastatic tumors.

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“…20 Several research groups have investigated the feasibility of using EV to transport pharmaceuticals, nucleic acids, and proteins for therapeutic purposes. 21,22 In this study, we identified potential candidate genes using an in vivo genetic loss-of-function screening approach based on CRISPR-Cas9 genome editing to identify genes that increase the sensitivity or cause radioresistance in an orthotopic GBM model. Ferroptosis, triggered by the enzyme glutathione synthetase (GSS), has been shown to be a determinant in radiosensitization.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, EV proteins include CD47, a transmembrane protein linked with integrins that helps shield cells from phagocytosis . Several research groups have investigated the feasibility of using EV to transport pharmaceuticals, nucleic acids, and proteins for therapeutic purposes. , …”

Section: Introductionmentioning

confidence: 99%

Engineered Extracellular Vesicle-Delivered CRISPR/Cas9 for Radiotherapy Sensitization of Glioblastoma

Liu,

Cao,

Wang

et al. 2023

ACS Nano

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Radiotherapy is a mainstay of glioblastoma (GBM) treatment; however, the development of therapeutic resistance has hampered the efficacy of radiotherapy, suggesting that additional treatment strategies are needed. Here, an in vivo loss-of-function genome-wide CRISPR screen was carried out in orthotopic tumors in mice subjected to radiation treatment to identify synthetic lethal genes associated with radiotherapy. Using functional screening and transcriptome analyses, glutathione synthetase (GSS) was found to be a potential regulator of radioresistance through ferroptosis. High GSS levels were closely related to poor prognosis and relapse in patients with glioma. Mechanistic studies demonstrated that GSS was associated with the suppression of radiotherapy-induced ferroptosis in glioma cells. The depletion of GSS resulted in the disruption of glutathione (GSH) synthesis, thereby causing the inactivation of GPX4 and iron accumulation, thus enhancing the induction of ferroptosis upon radiotherapy treatment. Moreover, to overcome the obstacles to broad therapeutic translation of CRISPR editing, we report a previously unidentified genome editing delivery system, in which Cas9 protein/sgRNA complex was loaded into Angiopep-2 (Ang) and the trans-activator of the transcription (TAT) peptide dual-modified extracellular vesicle (EV), which not only targeted the blood–brain barrier (BBB) and GBM but also permeated the BBB and penetrated the tumor. Our encapsulating EVs showed encouraging signs of GBM tissue targeting, which resulted in high GSS gene editing efficiency in GBM (up to 67.2%) with negligible off-target gene editing. These results demonstrate that a combination of unbiased genetic screens, and CRISPR-Cas9-based gene therapy is feasible for identifying potential synthetic lethal genes and, by extension, therapeutic targets.

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Tracking tools of extracellular vesicles for biomedical research

Cited by 17 publications

References 104 publications

Enhancement of the therapeutic efficacy of mesenchymal stem cell-derived exosomes in osteoarthritis

Enhancement of the therapeutic efficacy of mesenchymal stem cell-derived exosomes in osteoarthritis

Magnetic particle imaging reveals that iron-labeled extracellular vesicles accumulate in brains of mice with metastases

Engineered Extracellular Vesicle-Delivered CRISPR/Cas9 for Radiotherapy Sensitization of Glioblastoma

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