Stem Cell Extracellular Vesicles and their Potential to Contribute to the Repair of Damaged CNS Cells

Branscome, Heather; Paul, Siddhartha; Khatkar, Pooja; Kim, Yuriy; Barclay, Robert A.; Pinto, Daniel O.; Yin, Dameng; Zhou, Weidong; Liotta, Lance A.; El‐Hage, Nazira

doi:10.1007/s11481-019-09865-y

Cited by 27 publications

(35 citation statements)

References 113 publications

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“…Proteomic analysis showed that iPSC-EVs contained proteins involved in EGFR interactions and receptor tyrosine kinase signaling, while MSC-EVs contained proteins involved in insulin-like growth factor, Janus kinase ( JAK)signal transducer and activator of transcription (STAT), and Ras-related protein 1 pathways. 73 Three cytokines, FGF-2, VEGF, and IL-4, were observed to display significantly higher association with iPSC-EVs than MSC-EVs.…”

Section: Ipsc-derived Evs/exosomesmentioning

confidence: 92%

Human Pluripotent Stem Cell-Derived Extracellular Vesicles: Characteristics and Applications

Jeske

Bejoy

Marzano

et al. 2020

Tissue Engineering Part B: Reviews

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Extracellular vesicles (EVs), including exosomes and microvesicles, are found to play an important role in various biological processes and maintaining tissue homeostasis. Because of the protective effects, stem cellderived EVs can be used to reduce oxidative stress and apoptosis in the recipient cells. In addition, EVs/ exosomes have been used as directional communication tools between stem cells and parenchymal cells, giving them the ability to serve as biomarkers. Likewise, altered EVs/exosomes can be utilized for drug delivery by loading with proteins, small interfering RNAs, and viral vectors, in particular, because EVs/exosomes are able to cross the blood-brain barrier. In this review article, the properties of human induced pluripotent stem cell (iPSC)-derived EVs are discussed. The biogenesis, that is, how EVs originate in the endosomal compartment or from the cell layer of microvesicles, EV composition, the available methods of purification, and characterizations of EVs/exosomes are summarized. In particular, EVs/exosomes derived from iPSCs of different lineage specifications and the applications of these stem cell-derived exosomes in neurological diseases are discussed.

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Section: Ipsc-derived Evs/exosomesmentioning

confidence: 92%

Human Pluripotent Stem Cell-Derived Extracellular Vesicles: Characteristics and Applications

Jeske

Bejoy

Marzano

et al. 2020

Tissue Engineering Part B: Reviews

View full text Add to dashboard Cite

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“…Coculturing of donor infected cells with target cells is another widely used assay to identify cell-to-cell transmission. In this assay, infected target cells are harvested and cocultured with uninfected target cells under conditions that prevent infection by cell-free virus such as addition of neutralizing antibodies or blocking receptor binding ( Branscome et al, 2019 ; El Najjar et al, 2016 ; Martinez and Kielian, 2016 ; Xiao et al, 2014 ; Zhong et al, 2013 ). A fluorescent dye is usually used to differentiate target cells from donor cells, and quantification of cell spread is determined microscopically or by flow cytometry of a reporter virus or a labeled viral antigen.…”

Section: Experimental Approaches For Studying Cell-to-cell Spreadmentioning

confidence: 99%

Viral cell-to-cell spread: Conventional and non-conventional ways

Cifuentes-Muñoz

Najjar

Dutch

2020

Virus Assembly and Exit Pathways

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A critical step in the life cycle of a virus is spread to a new target cell, which generally involves the release of new viral particles from the infected cell which can then initiate infection in the next target cell. While cell-free viral particles released into the extracellular environment are necessary for long distance spread, there are disadvantages to this mechanism. These include the presence of immune system components, the low success rate of infection by single particles, and the relative fragility of viral particles in the environment. Several mechanisms of direct cell-to-cell spread have been reported for animal viruses which would avoid the issues associated with cell-free particles. A number of viruses can utilize several different mechanisms of direct cell-to-cell spread, but our understanding of the differential usage by these pathogens is modest. Although the mechanisms of cell-to-cell spread differ among viruses, there is a common exploitation of key pathways and components of the cellular cytoskeleton. Remarkably, some of the viral mechanisms of cell-to-cell spread are surprisingly similar to those used by bacteria. Here we summarize the current knowledge of the conventional and non-conventional mechanisms of viral spread, the common methods used to detect viral spread, and the impact that these mechanisms can have on viral pathogenesis.

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“…Moreover, we have observed distinct differences in EV-associated cytokines and lncRNAs among MSC and iPSC EVs (Branscome et al, 2019). This is a new and exciting area of research which deserves further attention to better characterize the effects of iPSC EVs both in vitro and in vivo in the context of CNS repair.…”

Section: Engineered Evsmentioning

confidence: 77%

“…Additionally, we recently detected VEGF and FGF-2, out of a total of 40 cytokines, as the two highest iPSC EV-associated cytokines. In an in vitro angiogenesis co-culture assay, significant increases in tubular length were observed in response to treatment with iPSC EVs (Branscome et al, 2019). A recent review has also highlighted other pro-angiogenic proteins that have been associated with MSC EVs; these include TGF-β1, IL-8, thrombopoietin, and MMPs (Merino-González et al, 2016).…”

Section: Proteomic Profiling Of Stem Cell Evsmentioning

confidence: 99%

Use of Stem Cell Extracellular Vesicles as a “Holistic” Approach to CNS Repair

Branscome

Paul

Yin

et al. 2020

Front. Cell Dev. Biol.

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Neurodegeneration is a hallmark of many diseases and disorders of the central nervous system (CNS). High levels of neuroinflammation are often associated with irreparable damage to CNS cells due to the dysregulation of signaling cascades that are unable to restore a homeostatic balance. Due to the inherent complexity of the CNS, development of CNS-related therapeutics has met limited success. While stem cell therapy has been evaluated in the context of CNS repair, the mechanisms responsible for their functional properties have not been clearly defined. In recent years, there has been growing interest in the use of stem cell extracellular vesicles (EVs) for the treatment of various CNS pathologies as these vesicles are believed to mediate many of the functional effects associated with their donor stem cells. The potency of stem cell EVs is believed to be largely driven by their biological cargo which includes various types of RNAs, proteins, and cytokines. In this review, we describe the characteristic properties of stem cell EVs and summarize their reported neuroprotective and immunomodulatory functions. A special emphasis is placed on the identification of specific biological cargo, including proteins and non-coding RNA molecules, that have been found to be associated with stem cell EVs. Collectively, this review highlights the potential of stem cell EVs as an alternative to traditional stem cell therapy for the repair of cellular damage associated with diverse CNS pathologies.

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Stem Cell Extracellular Vesicles and their Potential to Contribute to the Repair of Damaged CNS Cells

Cited by 27 publications

References 113 publications

Human Pluripotent Stem Cell-Derived Extracellular Vesicles: Characteristics and Applications

Human Pluripotent Stem Cell-Derived Extracellular Vesicles: Characteristics and Applications

Viral cell-to-cell spread: Conventional and non-conventional ways

Use of Stem Cell Extracellular Vesicles as a “Holistic” Approach to CNS Repair

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