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External magnetic-field driven delivery of exosomes modulates immune and metabolic changes of dystrophic muscle II

ABSTRACT: Exosomes are nanosized extracellular vesicles which have been recently demonstrated as promising agents for tissue repair/regeneration by inducing and guiding appropriate immune responses in dystrophic pathologies. Unfortunately, the accurate manipulation of exosomes by controlling their biodistribution still poses significant challenges. Here we overcome this limitation by developing an externally controlled delivery system for primed ANXA1 myo-exosomes (Exomyo). Effective nanocarriers are realized by immobilizing the Exomyo onto ferromagnetic nanotubes (NT-MAG) to achieve a controlled delivery and localization of Exomyo into skeletal muscles by an applied external magnetic field. Quantitative muscle-level analyses revealed that macrophages dominate the uptake of Exomyo from NT-MAG in vivo, to synergistically promote beneficial muscle responses in a murine animal model of Duchenne Muscular Dystrophy (DMD) thanks to the successful localization of therapeutic Exomyo upon systemic injection. These findings provide valuable insights into the development of exosome-based therapies for muscle diseases and in general highlight the formulation of effective functional nanocarriers aimed at optimizing exosome biodistribution.

ORGANISM(S): Mus musculus

PROVIDER: GSE263456 | GEO | 2024/07/23

REPOSITORIES: GEO

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External magnetic-field driven delivery of exosomes modulates immune and metabolic changes of dystrophic muscle I

Project description:Exosomes are nanosized extracellular vesicles which have been recently demonstrated as promising agents for tissue repair/regeneration by inducing and guiding appropriate immune responses in dystrophic pathologies. Unfortunately, the accurate manipulation of exosomes by controlling their biodistribution still poses significant challenges. Here we overcome this limitation by developing an externally controlled delivery system for primed ANXA1 myo-exosomes (Exomyo). Effective nanocarriers are realized by immobilizing the Exomyo onto ferromagnetic nanotubes (NT-MAG) to achieve a controlled delivery and localization of Exomyo into skeletal muscles by an applied external magnetic field. Quantitative muscle-level analyses revealed that macrophages dominate the uptake of Exomyo from NT-MAG in vivo, to synergistically promote beneficial muscle responses in a murine animal model of Duchenne Muscular Dystrophy (DMD) thanks to the successful localization of therapeutic Exomyo upon systemic injection. These findings provide valuable insights into the development of exosome-based therapies for muscle diseases and in general highlight the formulation of effective functional nanocarriers aimed at optimizing exosome biodistribution.

2024-07-23 | GSE263142 | GEO

Subcutaneous nanotherapy repurposes the immunosuppressive mechanism of rapamycin to enhance allogeneic islet graft viability

Project description:Oral rapamycin administration rapamycin is plagued by poor bioavailability and wide biodistribution. Thus, this pleotropic mTOR inhibitor has a narrow therapeutic window, numerous side effects and provides inadequate transplantation protection. Parental formulation was not possible due to rapamycin’s hydrophobicity (log P 4.3). Here, we demonstrate that subcutaneous rapamycin delivery via poly(ethylene glycol)-b-poly(propylene sulfide)(PEG-b-PPS) polymersome (PS) nanocarriers modulates cellular biodistribution of rapamycin to change its immunosuppressive mechanism for enhanced efficacy while minimizing side effects. While oral rapamycin inhibits naïve T cell proliferation directly, subcutaneously administered rapamycin-loaded polymersomes (rPS) instead modulated Ly-6Clow monocytes and tolerogenic semi-mature dendritic cells, with immunosuppression mediated by CD8+ Tregs and rare CD4+ CD8+ double-positive T cells. As PEG-b-PPS PS are uniquely non-inflammatory, background immunostimulation from the vehicle was avoided, allowing immunomodulation to be primarily attributed to rapamycin’s cellular biodistribution. Repurposing mTOR inhibition significantly improved maintenance of normoglycemia in a clinically relevant, MHC-mismatched, allogeneic, intraportal (liver) islet transplantation model. These results demonstrate the ability of engineered nanocarriers to repurpose drugs for alternate routes of administration by rationally controlling cellular biodistribution.

2022-01-01 | GSE182776 | GEO

The effect of high or low fat diet on the miRNA composition of exosomes derived from adipose tissue

Project description:Exosomes are nanosized extracellular vesicles with lipid bilayer membranes and contain various contents, including lipids, miRNAs and proteins, all of which are widely involved in signaling pathways and genetic information processes. Exosomes derived from adipose tissues (AT-Exos) have been identified as a crucialmedium in the transmission of information from adipose tissue to itself and to other organs, including exosomes derived from inguinal white adipose tissue (iWAT-Exos), visceral white adipose tissue (vWAT-Exos) and brown adipose tissue (BAT-Exos). Here we reported that dietary conditions and tissue origins of exosome can affect the composition and function of miRNAs in AT-Exos, mainly including lipid metabolism and inflammatory signaling pathways associated with metabolic imbalance.

2024-04-25 | GSE264481 | GEO

Identification of a circulating miRNA that is involved in meat yield and connects exosomes and longissimus dorsi muscle in Korean cattle steers

Project description:MicroRNAs (miRNAs) regulate gene expression. The aim of this study was to identify circulating miRNAs that are involved with meat yield and connect exosomes and longissimus dorsi (LD) muscle in Korean cattle steer. Thus, we performed analyses of the carcass characteristics, exosome extraction, bovine miRNA array, mature miRNA qPCR, bioinformatics, and qPCR. Our analysis of the carcass characteristics relative to the yield grade (YG) showed that the yield index (YI) and rib eye area were the highest, whereas the backfat thickness was the lowest for YG A cattle among the three YGs. We performed a miRNA microarray and a Venn diagram analysis to sort the circulating miRNAs that connect exosomes and LD muscle. Mature miRNA qPCR showed that miR-15a (r = 0.84), miR-26b (r = 0.91), and miR-29c (r = 0.92) had positive relationships with exosomes and LD muscle. In YG A cattle, miR-26b was considered to be a circulating miRNA connecting exosomes and LD muscle because the expression pattern of miR-26b was similar in the microarray and miRNA qPCR for miR-26b-targeted genes, where the expression levels of DIAPH3 and YOD1 were lower than those in YG C cattle. Our results suggest that circulating miR-26b may participate in cell maintenance by regulating DIAPH3 and YOD1 in the LD muscle of Korean cattle. 29 or 30 month Korean cattle steers were classified by yield grade(YG) A, B, and C. miRNA expression patterns for exosome and LD muscle were compared among YGs.

2016-03-01 | E-GEOD-73389 | biostudies-arrayexpress

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Project description:While recent clinical studies demonstrate the promise of cancer immunotherapy, a barrier for broadening the clinical benefit is identifying how tumors locally suppress cytotoxic immunity. As an emerging mode of intercellular communication, exosomes secreted by malignant cells can deliver a complex payload of coding and non-coding RNA to cells within the tumor microenvironment. Here, we quantified the RNA payload within tumor-derived exosomes and the resulting dynamic transcriptomic response to cytotoxic T cells upon exosome delivery to better understand how tumor-derived exosomes can alter immune cell function. Exosomes derived from B16F0 melanoma cells were enriched for a subset of coding and non-coding RNAs that did not reflect the abundance in the parental cell. Upon exosome delivery, RNAseq revealed the dynamic changes in the transcriptome of CTLL2 cytotoxic T cells. In analyzing transiently co-expressed gene clusters, pathway enrichment suggested that the B16F0 exosomal payload altered mitochondrial respiration, which was confirmed independently, and upregulated genes associated with the Notch signaling pathway. Interestingly, exosomal miRNA appeared to have no systematic effect on downregulating target mRNA levels.

2018-03-13 | GSE103000 | GEO

bladder cancer patient urine exosomes

Project description:Extracellular vesicles (EVs), particularly nano-sized small EV exosomes, are emerging biomarker sources. However, due to heterogeneous populations secreted from diverse cell types, mapping exosome multi-omic molecular information specifically to their pathogenesis origin for cancer biomarker identification is still extraordinarily challenging. Herein, we introduced a novel 3D-structured nanographene immunomagnetic particles (NanoPoms) with unique flower pom-poms morphology and photo-click chemistry for specific marker-defined capture and release of intact exosome. This specific exosome isolation approach leads to the expanded identification of targetable cancer biomarkers with enhanced specificity and sensitivity, as demonstrated by multi-omic exosome analysis of bladder cancer patient tissue fluids using the next generation sequencing of somatic DNA mutations, miRNAs, and the global proteome. The NanoPoms prepared exosomes also exhibit distinctive in vivo biodistribution patterns, highlighting the highly viable and integral quality. The developed method is simple and straightforward, which is applicable to nearly all types of biological fluids and amenable for enrichment, scale up, and high-throughput exosome isolation.

2022-08-12 | PXD034454 | Pride

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2022-03-02 | GSE185654 | GEO

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2020-03-13 | E-MTAB-8376 | biostudies-arrayexpress

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