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A call for the standardised reporting of factors affecting the exogenous loading of extracellular vesicles with therapeutic cargos.

ABSTRACT: Extracellular vesicles (EVs) are complex nanoparticles required for the intercellular transfer of diverse biological cargoes. Unlike synthetic nanoparticles, EVs may provide a natural platform for the enhanced targeting and functional transfer of therapeutics across complex and often impenetrable biological boundaries (e.g. the blood-brain barrier or the matrix of densely organised tumours). Consequently, there is considerable interest in utilising EVs as advanced drug delivery systems for the treatment of a range of challenging pathologies. Within the past decade, efforts have focused on providing standard minimal requirements for conducting basic EV research. However, no standard reporting framework has been established governing the therapeutic loading of EVs for drug delivery applications. The purpose of this review is to critically evaluate progress in the field, providing an initial set of guidelines that can be applied as a benchmark to enhance reproducibility and increase the likelihood of translational outcomes.

SUBMITTER: Rankin-Turner S

PROVIDER: S-EPMC8191593 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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A call for the standardised reporting of factors affecting the exogenous loading of extracellular vesicles with therapeutic cargos.

Rankin-Turner Stephanie S Vader Pieter P O'Driscoll Lorraine L Giebel Bernd B Heaney Liam M LM Davies Owen G OG

Advanced drug delivery reviews 20210420

Extracellular vesicles (EVs) are complex nanoparticles required for the intercellular transfer of diverse biological cargoes. Unlike synthetic nanoparticles, EVs may provide a natural platform for the enhanced targeting and functional transfer of therapeutics across complex and often impenetrable biological boundaries (e.g. the blood-brain barrier or the matrix of densely organised tumours). Consequently, there is considerable interest in utilising EVs as advanced drug delivery systems for the t ...[more]

PMID: 33862168

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Project description:BackgroundSmall extracellular vesicles from adipose-derived stem cells (ASC-sEVs) have gained remarkable attention for their regenerative and protective properties against skin aging. However, the use of ASC-sEVs to further encapsulate certain natural anti-aging compounds for synergistic effects has not been actively explored. For large-scale production in skincare industry, it is also crucial to standardize cost-effective methods to produce highly pure ASC-sEVs.MethodsHuman ASCs were expanded in serum-free media with different compositions to first optimize the sEV production. ASC-sEVs from different batches were then purified using tangential flow filtration and sucrose cushion ultracentrifugation, followed by extensive characterization for identity and content profiling including proteomics, lipidomics and miRNA sequencing. ASC-sEVs were further loaded with nicotinamide riboside (NR) and resveratrol by sonication-incubation method. The therapeutic effect of ASC-sEVs and loaded ASC-sEVs was tested on human keratinocyte cell line HaCaT exposed to UVB by measuring reactive oxygen species (ROS). The loaded ASC-sEVs were later applied on the hand skin of three volunteers once a day for 8 weeks and skin analysis was performed every 2 weeks.ResultsOur standardized workflow produced ASC-sEVs with high yield, high purity and with stable characteristics and consistent biocargo among different batches. The most abundant subpopulations in ASC-sEVs were CD63+ (∼30%) and CD81+ -CD63+ (∼35%). Purified ASC-sEVs could be loaded with NR and resveratrol at the optimized loading efficiency of ∼20%. In UVB-exposed HaCaT cells, loaded ASC-sEVs could reduce ROS by 38.3%, higher than the sEVs (13.3%) or compounds (18.5%) individually. In human trial, application of loaded ASC-sEVs after 8 weeks substantially improved skin texture, increased skin hydration and elasticity by 104% and reduced mean pore volume by 51%.ConclusionsThis study demonstrated a robust protocol to produce ASC-sEVs and exogenously load them with natural compounds. The loaded ASC-sEVs exhibited synergistic effects of both sEVs and anti-aging compounds in photoaging protection and skin rejuvenation.

Project description:BackgroundMacrophages are highly plastic innate immune cells that play key roles in host defense, tissue repair, and homeostasis maintenance. In response to divergent stimuli, macrophages rapidly alter their functions and manifest a wide polarization spectrum with two extremes: M1 or classical activation and M2 or alternative activation. Extracellular vesicles (EVs) secreted from differentially activated macrophages have been shown to have diverse functions, which are primarily attributed to their microRNA cargos. The role of protein cargos in these EVs remains largely unexplored. Therefore, in this study, we focused on the protein cargos in macrophage-derived EVs.ResultsNaïve murine bone marrow-derived macrophages were treated with lipopolysaccharide or interlukin-4 to induce M1 or M2 macrophages, respectively. The proteins of EVs and their parental macrophages were subjected to quantitative proteomics analyses, followed by bioinformatic analyses. The enriched proteins of M1-EVs were involved in proinflammatory pathways and those of M2-EVs were associated with immunomodulation and tissue remodeling. The signature proteins of EVs shared a limited subset of the proteins of their respective progenitor macrophages, but they covered many of the typical pathways and functions of their parental cells, suggesting their respective M1-like and M2-like phenotypes and functions. Experimental examination validated that protein cargos in M1- or M2-EVs induced M1 or M2 polarization, respectively. More importantly, proteins in M1-EVs promoted viability, proliferation, and activation of T lymphocytes, whereas proteins in M2-EVs potently protected the tight junction structure and barrier integrity of epithelial cells from disruption. Intravenous administration of M2-EVs in colitis mice led to their accumulation in the colon, alleviation of colonic inflammation, promotion of M2 macrophage polarization, and improvement of gut barrier functions. Protein cargos in M2-EVs played a key role in their protective function in colitis.ConclusionThis study has yielded a comprehensive unbiased dataset of protein cargos in macrophage-derived EVs, provided a systemic view of their potential functions, and highlighted the important engagement of protein cargos in the pathophysiological functions of these EVs.

Dataset Information

A call for the standardised reporting of factors affecting the exogenous loading of extracellular vesicles with therapeutic cargos.

Publications

A call for the standardised reporting of factors affecting the exogenous loading of extracellular vesicles with therapeutic cargos.

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