Extracellular vesicles for personalized medicine: The input of physically triggered production, loading and theranostic properties

Piffoux, Max; Nicolas‐Boluda, Alba; Mulens-Arias, Vladmir; Richard, Sophie; Rahmi, Gabriel; Gazeau, Florence; Wilhelm, Claire; Silva, Amanda

doi:10.1016/j.addr.2018.12.009

Cited by 95 publications

(89 citation statements)

References 153 publications

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“…EVs are of great interest and importance in drug delivery. The promising advantages of low immunogenicity, intrinsic cell targeting properties, and enhanced stability in circulation make them more and more attractive in targeted drug therapy (Liao et al, 2019;Piffoux et al, 2019). They have been revealed huge potentials in the therapy of various diseases including malignancies and neurology diseases (Bunggulawa et al, 2018;Khan et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Prospects and challenges of extracellular vesicle-based drug delivery system: considering cell source

et al. 2020

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Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, are nanosized membrane vesicles derived from most cell types. Carrying diverse biomolecules from their parent cells, EVs are important mediators of intercellular communication and thus play significant roles in physiological and pathological processes. Owing to their natural biogenesis process, EVs are generated with high biocompatibility, enhanced stability, and limited immunogenicity, which provide multiple advantages as drug delivery systems (DDSs) over traditional synthetic delivery vehicles. EVs have been reported to be used for the delivery of siRNAs, miRNAs, protein, small molecule drugs, nanoparticles, and CRISPR/Cas9 in the treatment of various diseases. As a natural drug delivery vectors, EVs can penetrate into the tissues and be bioengineered to enhance the targetability. Although EVs' characteristics make them ideal for drug delivery, EV-based drug delivery remains challenging, due to lack of standardized isolation and purification methods, limited drug loading efficiency, and insufficient clinical grade production. In this review, we summarized the current knowledge on the application of EVs as DDS from the perspective of different cell origin and weighted the advantages and bottlenecks of EV-based DDS. ARTICLE HISTORY

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Section: Discussionmentioning

confidence: 99%

Prospects and challenges of extracellular vesicle-based drug delivery system: considering cell source

et al. 2020

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“…In general, EVs are classified into three major groups: exosomes, microvesicles and apoptotic bodies based on vesicle diameter and the release process (26). Exosomes are the smallest vesicles (~ 50 -100 nm) released through exocytosis of endosomal multivesicular bodies.…”

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confidence: 99%

Programmable Modulation for Extracellular Vesicles

Wang

Melvin

Bemis

et al. 2019

Preprint

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Every living cell releases extracellular vesicles (EVs) that are critical for cellular signaling and a wide range of biological functions. The potential diagnostic and therapeutic applications of EVs are well recognized, and rapidly expanding. While a complete understanding of the molecular mechanisms underpinning EVs release remains elusive, here we demonstrate a novel method for programmable control of the release of EVs and their cargo using external electric fields. As a proof of principle, we use cultured rat astrocytes to demonstrate how the frequency of external electrical stimulation selectively modulates EV release, their surface proteins, and microRNA profiles. This method could broadly impact biological science and medical applications. First, it raises an interesting question of how endogenous electrical activity could modulate EV production. Second, it provides a novel mechanism for tuning therapeutic electrical stimulation that may be useful for treating brain disorders. Third, it provides a new way to generate EVs carrying desired cargos by tuning electrical stimulation parameters. Unlike chemical methods for creating EVs, electrical stimulation is a clean physical method with adjustable parameters including stimulation frequency, field strength and waveform morphology.

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“…It has been reported that MSC culture and EV production in hypoxic conditions (1–5% O 2 ) increase the number of EVs released and their cargo composition (growth factors and miRNAs), thus enhancing their pro-angiogenic, immunomodulatory, cardioprotective and neuroprotective effects ( Cui et al, 2018 ; Xue et al, 2018 ; Zhu et al, 2018 ). Another option is to take advantage of bioreactors to mechanically stimulate EV production by applying fluid shear stress or compression [for review, see Piffoux et al (2019) ]. Although, the underlying mechanisms are not known, one hypothesis is that in this condition, MSCs inhibit their own re-uptake of EVs.…”

Section: Challenges For the Industrial Production Of Gmp-grade Extracmentioning

confidence: 99%

Mesenchymal Stem Cell-Derived Extracellular Vesicles: Opportunities and Challenges for Clinical Translation

Maumus

Rozier

Boulestreau

et al. 2020

Front. Bioeng. Biotechnol.

112

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Extracellular vesicles (EVs), including exosomes and microvesicles, derived from mesenchymal stem/stromal cells (MSCs) exert similar effects as their parental cells, and are of interest for various therapeutic applications. EVs can act through uptake by the target cells followed by release of their cargo inside the cytoplasm, or through interaction of membrane-bound ligands with receptors expressed on target cells to stimulate downstream intracellular pathways. EV-based therapeutics may be directly used as substitutes of intact cells or after modification for targeted drug delivery. However, for the development of EV-based therapeutics, several production, isolation, and characterization requirements have to be met and the quality of the final product has to be tested before its clinical implementation. In this review, we discuss the challenges associated with the development of EV-based therapeutics and the regulatory specifications for their successful clinical translation.

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Extracellular vesicles for personalized medicine: The input of physically triggered production, loading and theranostic properties

Cited by 95 publications

References 153 publications

Prospects and challenges of extracellular vesicle-based drug delivery system: considering cell source

Prospects and challenges of extracellular vesicle-based drug delivery system: considering cell source

Programmable Modulation for Extracellular Vesicles

Mesenchymal Stem Cell-Derived Extracellular Vesicles: Opportunities and Challenges for Clinical Translation

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