Isolation of Exosome-Enriched Extracellular Vesicles Carrying Granulocyte-Macrophage Colony-Stimulating Factor from Embryonic Stem Cells

Meng, Shuhan; Whitt, Aaron G.; Tu, Allison; Eaton, John W.; Li, Chi; Yaddanapudi, Kavitha

doi:10.3791/60170

Cited by 3 publications

(3 citation statements)

References 26 publications

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“…Meng et al proved the presence of large amounts of granulocyte-macrophage colony-stimulating factor (GM-CSF) in exosomes, which have the potential to enhance immunomodulatory function and benefit SCI repair. 224 Zhou et al showed that anti-inflammatory microgliaderived M2-Exos had a better ability to promote the recovery of functional behavior, increasing axon regeneration and reducing the level of pyroptosis in spinal cord neurons after SCI. M2-Exos rich in miR-672-5p could inhibit the AIM2/ASC/caspase-1 signaling pathway by inhibiting AIM2 activity to inhibit neuronal pyroptosis and ultimately promote the recovery of functional behavior in mice with SCI.…”

Section: Intervention and Repair Of Scimentioning

confidence: 99%

Spinal cord injury: molecular mechanisms and therapeutic interventions

Ren

et al. 2023

Sig Transduct Target Ther

165

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Spinal cord injury (SCI) remains a severe condition with an extremely high disability rate. The challenges of SCI repair include its complex pathological mechanisms and the difficulties of neural regeneration in the central nervous system. In the past few decades, researchers have attempted to completely elucidate the pathological mechanism of SCI and identify effective strategies to promote axon regeneration and neural circuit remodeling, but the results have not been ideal. Recently, new pathological mechanisms of SCI, especially the interactions between immune and neural cell responses, have been revealed by single-cell sequencing and spatial transcriptome analysis. With the development of bioactive materials and stem cells, more attention has been focused on forming intermediate neural networks to promote neural regeneration and neural circuit reconstruction than on promoting axonal regeneration in the corticospinal tract. Furthermore, technologies to control physical parameters such as electricity, magnetism and ultrasound have been constantly innovated and applied in neural cell fate regulation. Among these advanced novel strategies and technologies, stem cell therapy, biomaterial transplantation, and electromagnetic stimulation have entered into the stage of clinical trials, and some of them have already been applied in clinical treatment. In this review, we outline the overall epidemiology and pathophysiology of SCI, expound on the latest research progress related to neural regeneration and circuit reconstruction in detail, and propose future directions for SCI repair and clinical applications.

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Section: Intervention and Repair Of Scimentioning

confidence: 99%

Spinal cord injury: molecular mechanisms and therapeutic interventions

Ren

et al. 2023

Sig Transduct Target Ther

165

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“…Exosomes are rich in a large number of bioactive molecules, which exert many important functions both in vitro and in vivo. Meng et al proved the presence of large amounts of granulocyte–macrophage colony stimulating factor (GM-CSF) in exosomes, which have the potential to enhance the immunomodulatory function [ 44 ]. Sun et al demonstrated that patients with metastatic colorectal cancer had higher serum levels of exosome-derived ADAM17 and that exosomal ADAM17 could facilitate colorectal cancer cell migration by cleaving the E-cadherin junction [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Biocompatible exosome-modified fibrin gel accelerates the recovery of spinal cord injury by VGF-mediated oligodendrogenesis

Yang

Dong

et al. 2022

J Nanobiotechnol

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Exosomes show potential for treating patients with spinal cord injury (SCI) in clinical practice, but the underlying repair mechanisms remain poorly understood, and biological scaffolds available for clinical transplantation of exosomes have yet to be explored. In the present study, we demonstrated the novel function of Gel-Exo (exosomes encapsulated in fibrin gel) in promoting behavioural and electrophysiological performance in mice with SCI, and the upregulated neural marker expression in the lesion site suggested enhanced neurogenesis by Gel-Exo. According to the RNA-seq results, Vgf (nerve growth factor inducible) was the key regulator through which Gel-Exo accelerated recovery from SCI. VGF is related to myelination and oligodendrocyte development according to previous reports. Furthermore, we found that VGF was abundant in exosomes, and Gel-Exo-treated mice with high VGF expression indeed showed increased oligodendrogenesis. VGF was also shown to promote oligodendrogenesis both in vitro and in vivo, and lentivirus-mediated VGF overexpression in the lesion site showed reparative effects equal to those of Gel-Exo treatment in vivo. These results suggest that Gel-Exo can thus be used as a biocompatible material for SCI repair, in which VGF-mediated oligodendrogenesis is the vital mechanism for functional recovery.

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“…This includes several ligands for major receptor families, such as the TNF family receptor ligands (e.g., CD95L (FasL) (Audo et al, 2012;Kim et al, 2005), TRAIL (Wajant, 2006), TNF alpha (Zhang et al, 2006), CD40L (Martínez et al, 2022), OX40L (Neyrinck-Leglantier et al, 2022, CD70 (Himbert et al, 2020), CD30L (Hansen et al, 2014(Hansen et al, , 2016 and RANKL (Wnt (Gross et al, 2012;Holliday et al, 2021))) and Wnt ligands (Torres et al, 2021) as well as ligands belonging to the Ig superfamily (e.g., PD-L1 (Martínez et al, 2022), CD80 (Liu et al, 2023), and CD66a/CEACAM1 (Igami et al, 2022)). Additionally, ligands for receptor tyrosine kinases such as VEGF (Zeng & Fu, 2019), colony-stimulating factors (Meng et al, 2021), and epidermal growth factors (Frawley & Piskareva, 2020) 2008; Li et al, 1999;Matsumoto et al, 2015;Richter et al, 2012;Suda et al, 1997). This is likely due to the VIRS effect, which can potentiate the local accumulation of the corresponding receptors, thereby enhancing their signalling capacity.…”

Section:  the Ev Membrane As Protein Presentation Platformmentioning

confidence: 99%

Membranes on the move: The functional role of the extracellular vesicle membrane for contact‐dependent cellular signalling

Jahnke,

Staufer

2024

J of Extracellular Vesicle

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Extracellular vesicles (EVs), lipid‐enclosed structures released by virtually all life forms, have gained significant attention due to their role in intercellular and interorganismal communication. Despite their recognized importance in disease processes and therapeutic applications, fundamental questions about their primary function remain. Here, we propose a different perspective on the primary function of EVs, arguing that they serve as essential elements providing membrane area for long‐distance, contact‐dependent cellular communication based on protein‐protein interaction. While EVs have been recognized as carriers of genetic information, additional unique advantages that they could provide for cellular communication remain unclear. Here, we introduce the concept that the substantial membrane area provided by EVs allows for membrane contact‐dependent interactions that could be central to their function. This membrane area enables the lateral diffusion and sorting of membrane ligands like proteins, polysaccharides or lipids in two dimensions, promoting avidity‐driven effects and assembly of co‐stimulatory architectures at the EV‐cell interface. The concept of vesicle‐induced receptor sequestration (VIRS), for example, describes how EVs confine and focus receptors at the EV contact site, promoting a dense local concentration of receptors into signalosomes. This process can increase the signalling strength of EV‐presented ligands by 10‐1000‐fold compared to their soluble counterparts. The speculations in this perspective advance our understanding of EV‐biology and have critical implications for EV‐based applications and therapeutics. We suggest a shift in perspective from viewing EVs merely as transporters of relevant nucleic acids and proteins to considering their unique biophysical properties as presentation platforms for long‐distance, contact‐dependent signalling. We therefore highlight the functional role of the EV membrane rather than their content. We further discuss how this signalling mechanism might be exploited by virus‐transformed or cancer cells to enhance immune‐evasive mechanisms.

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Isolation of Exosome-Enriched Extracellular Vesicles Carrying Granulocyte-Macrophage Colony-Stimulating Factor from Embryonic Stem Cells

Cited by 3 publications

References 26 publications

Spinal cord injury: molecular mechanisms and therapeutic interventions

Spinal cord injury: molecular mechanisms and therapeutic interventions

Biocompatible exosome-modified fibrin gel accelerates the recovery of spinal cord injury by VGF-mediated oligodendrogenesis

Membranes on the move: The functional role of the extracellular vesicle membrane for contact‐dependent cellular signalling

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