Exosomes as therapeutics: The implications of molecular composition and exosomal heterogeneity

Ferguson, Scott; Nguyen, Juliane

doi:10.1016/j.jconrel.2016.02.037

Cited by 305 publications

(249 citation statements)

References 114 publications

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“…Detection of EVs in biological fluids can be used as diagnostic, prognostic, and treatment monitoring biomarker [36]. EVs lipid bilayer membrane includes transmembrane proteins and encloses soluble proteins and nucleic acids derived from the cell of origin [37]. EVs are able to shuttle protein, lipids, carbohydrates, messenger RNAs, long noncoding RNAs, microRNAs, mitochondrial DNA, and chromosomal DNA into target cells [38, 39].…”

Section: Cell-derived Vesiclesmentioning

confidence: 99%

“…Albeit several regulatory and technical issues in achieving highly purified and extensively characterized EVs preparations suitable for use in humans need to be solved [37, 50], several clinical trials have been conducted. Ohno et al [41] recently reviewed the results of the phase I clinical trials of EVs-based therapies.…”

Section: Cell-derived Vesiclesmentioning

confidence: 99%

“…In biodistribution studies, the dosage of administered EVs is mainly assessed by determining the protein content in EVs preparations, which, due to suboptimal isolation protocols, may suffer from protein aggregates contaminations [112]. Furthermore, EVs display an intrinsic broad size distribution and heterogeneity, which may determine differential targeting [37]. Differential posttranslational modifications of EVs membrane proteins are an additional source of variability, which might have a functional role in EVs specific targeting [113].…”

Section: Investigating Extracellular Vesicles Biodistribution By Mmentioning

confidence: 99%

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Towards Therapeutic Delivery of Extracellular Vesicles: Strategies for In Vivo Tracking and Biodistribution Analysis

Rocco¹,

Baldari²,

Toietta³

2016

Stem Cells International

120

101

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Extracellular vesicles (EVs), such as microvesicles and exosomes, are membranous structures containing bioactive material released by several cells types, including mesenchymal stem/stromal cells (MSCs). Increasing lines of evidences point to EVs as paracrine mediators of the beneficial effects on tissue remodeling associated with cell therapy. Administration of MSCs-derived EVs has therefore the potential to open new and safer therapeutic avenues, alternative to cell-based approaches, for degenerative diseases. However, an enhanced knowledge about in vivo EVs trafficking upon delivery is required before effective clinical translation. Only a few studies have focused on the biodistribution analysis of exogenously administered MSCs-derived EVs. Nevertheless, current strategies for in vivo tracking in animal models have provided valuable insights on the biodistribution upon systemic delivery of EVs isolated from several cellular sources, indicating in liver, spleen, and lungs the preferential target organs. Different strategies for targeting EVs to specific tissues to enhance their therapeutic efficacy and reduce possible off-target effects have been investigated. Here, in the context of a possible clinical application of MSC-derived EVs for tissue regeneration, we review the existing strategies for in vivo tracking and targeting of EVs isolated from different cellular sources and the studies elucidating the biodistribution of exogenously administered EVs.

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Section: Cell-derived Vesiclesmentioning

confidence: 99%

Section: Cell-derived Vesiclesmentioning

confidence: 99%

Section: Investigating Extracellular Vesicles Biodistribution By Mmentioning

confidence: 99%

See 1 more Smart Citation

Towards Therapeutic Delivery of Extracellular Vesicles: Strategies for In Vivo Tracking and Biodistribution Analysis

Rocco¹,

Baldari²,

Toietta³

2016

Stem Cells International

120

101

View full text Add to dashboard Cite

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“…The exact mechanism behind the therapeutic effect of MSC-derived EVs remains largely obscure and is a topic of intensive investigation [100]. It is however known that stem cell EVs are enriched in signaling proteins, including cytokines, chemokines, interleukins and growth factors [101]. The use of EVs as a surrogate for cell-based therapies is intensively studied as it might entail some benefits.…”

Section: Harnessing the Intrinsic Biological Effect Of Evsmentioning

confidence: 99%

Therapeutic and diagnostic applications of extracellular vesicles

Stremersch

Smedt

Raemdonck

2016

Journal of Controlled Release

156

103

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During the past two decades, extracellular vesicles (EVs) have been identified as important mediators of intercellular communication, enabling the functional transfer of bioactive molecules from one cell to another. Consequently, it is becoming increasingly clear that these vesicles are involved in many (patho)physiological processes, providing opportunities for therapeutic applications. Moreover, it is known that the molecular composition of EVs reflects the physiological status of the producing cell and tissue, rationalizing their exploitation as biomarkers in various diseases. In this review the composition, biogenesis and diversity of EVs is discussed in a therapeutic and diagnostic context. We describe emerging therapeutic applications, including the use of EVs as drug delivery vehicles and as cell-free vaccines, and reflect on future challenges for clinical translation. Finally, we discuss the use of EVs as a biomarker source and highlight recent studies and clinical successes.

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“…Exosomes are vesicles with a diameter of 20-100 nm formed by the inward budding of endosomal membranes to form large multivesicular bodies and released extracellularly when MVBs fuse with the plasma membrane. Larger microvesicles with diameter of 100 nm-1 mm result from the direct outward budding and fission of the plasma membrane (2).…”

mentioning

confidence: 99%