Extracellular Vesicles as Natural Nanosized Delivery Systems for Small-Molecule Drugs and Genetic Material: Steps towards the Future Nanomedicines

Kotmakçı, Mustafa; Çetintaş, Vildan Bozok

doi:10.18433/j36w3x

Cited by 46 publications

(31 citation statements)

References 123 publications

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“…Therefore, detargeting from macrophages or targeting of EVs to specific tissues may enhance their therapeutic efficacy and reduce possible off-target effects. In order to achieve targeted delivery different strategies to modify EVs' natural tropism have been developed (Table 2) [119–121]. Some approaches require the functionalization of the cellular source to generate “tailored” EVs (Figure 2).…”

Section: Targeting Extracellular Vesicles Deliverymentioning

confidence: 99%

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: Targeting Extracellular Vesicles Deliverymentioning

confidence: 99%

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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“…Nucleic acid delivery methods, such as microinjection, in vitro electroporation, viral transduction and liposomal transfection, have defects [14]. Given that EVs-natural nanosized shuttles-are novel tools for delivering biomolecules to target cells [15][16][17][18], exploring the characteristics of OVS might also provide novel methods for delivering exogenous nucleic acids into preimplantation embryos.…”

Section: Introductionmentioning

confidence: 99%

Extracellular Vesicles Function as Bioactive Molecular Transmitters in the Mammalian Oviduct: An Inspiration for Optimizing in Vitro Culture Systems and Improving Delivery of Exogenous Nucleic Acids during Preimplantation Embryonic Development

Liu

2020

IJMS

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Two technologies, in vitro culture and exogenous gene introduction, constitute cornerstones of producing transgenic animals. Although in vitro embryo production techniques can bypass the oviduct during early development, such embryos are inferior to their naturally produced counterparts. In addition, preimplantation embryos are resistant to the uptake of exogenous genetic material. These factors restrict the production of transgenic animals. The discovery of extracellular vesicles (EVs) was a milestone in the study of intercellular signal communication. EVs in the oviduct, known as oviductosomes (OVS), are versatile delivery tools during maternal–embryo communication. In this review, we discuss the important roles of OVS in these interactions and the feasibility of using them as tools for transferring exogenous nucleic acids during early development. We hypothesize that further accurate characterization of OVS cargoes and functions will open new horizons for research on maternal–embryo interactions and enhance the production of transgenic animals.

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“…Additionally, miRNAs from MSC-EV have been shown to influence cardiac regeneration and protection (Nouraee and Mowla, 2015). Strategies for loading and modifying the EV-cargo exist; electroporation, freeze-thaw cycles, saponin-mediated loading, and hypotonic dialysis have all been studied for use in exogenously loading EV (Kotmakçı and Çetintaş, 2015;Mendt et al, 2018). EV cargo may also influence EV migration.…”

Section: Biodistribution and Targeting Of Msc-ev To Target Tissuesmentioning

confidence: 99%

Mesenchymal Stem Cell-Derived Extracellular Vesicles: Challenges in Clinical Applications

Gowen

Shahjin

Chand

et al. 2020

Front. Cell Dev. Biol.

254

203

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Stem cell therapy has garnered much attention and application in the past decades for the treatment of diseases and injuries. Mesenchymal stem cells (MSCs) are studied most extensively for their therapeutic roles, which appear to be derived from their paracrine activity. Recent studies suggest a critical therapeutic role for extracellular vesicles (EV) secreted by MSCs. EV are nano-sized membrane-bound vesicles that shuttle important biomolecules between cells to maintain physiological homeostasis. Studies show that EV from MSCs (MSC-EV) have regenerative and anti-inflammatory properties. The use of MSC-EV, as an alternative to MSCs, confers several advantages, such as higher safety profile, lower immunogenicity, and the ability to cross biological barriers, and avoids complications that arise from stem cell-induced ectopic tumor formation, entrapment in lung microvasculature, and immune rejection. These advantages and the growing body of evidence suggesting that MSC-EV display therapeutic roles contribute to the strong rationale for developing EV as an alternative therapeutic option. Despite the success in preclinical studies, use of MSC-EV in clinical settings will require careful consideration; specifically, several critical issues such as (i) production methods, (ii) quantification and characterization, (iii) pharmacokinetics, targeting and transfer to the target sites, and (iv) safety profile assessments need to be resolved. Keeping these issues in mind, the aim of this mini-review is to shed light on the challenges faced in MSC-EV research in translating successful preclinical studies to clinical platforms.

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Extracellular Vesicles as Natural Nanosized Delivery Systems for Small-Molecule Drugs and Genetic Material: Steps towards the Future Nanomedicines

Cited by 46 publications

References 123 publications

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

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

Extracellular Vesicles Function as Bioactive Molecular Transmitters in the Mammalian Oviduct: An Inspiration for Optimizing in Vitro Culture Systems and Improving Delivery of Exogenous Nucleic Acids during Preimplantation Embryonic Development

Mesenchymal Stem Cell-Derived Extracellular Vesicles: Challenges in Clinical Applications

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