The heterogeneous populations of exosomes with distinct nanosize have impeded our understanding of their corresponding function as intercellular communication agents. Profiling signaling proteins packaged in each size-dependent subtype can disclose this heterogeneity of exosomes. Herein, new strategy was developed for deconstructing heterogeneity of distinct-size urine exosome subpopulations by profiling N-glycoproteomics and phosphoproteomics simultaneously. Two-dimension size exclusion liquid chromatography (SEC) was utilized to isolate large exosomes (L-Exo), medium exosomes (M-Exo), and small exosomes (S-Exo) from human urine samples. Then, hydrophilic carbonyl-functionalized magnetic zirconium-organic framework (CFMZOF) was developed as probe for capturing the two kinds of post-translational modification (PTM) peptides simultaneously. Finally, liquid chromatography-tandem mass spectrometry (LC-MS/MS) combined with database search was used to characterize PTM protein contents. We identified 144 glycoproteins and 44 phosphoproteins from L-Exo, 156 glycoproteins, and 46 phosphoproteins from M-Exo and 134 glycoproteins and 10 phosphoproteins from S-Exo. The ratio of the proteins with simultaneous glycosylation and phosphorylation is 11%, 9%, and 3% in L-Exo, M-Exo, and S-Exo, respectively. Based on label-free quantification intensity results, both principal component analysis and Pearson’s correlation coefficients indicate that distinct-size exosome subpopulations exist significant differences in PTM protein contents. Analysis of high abundance PTM proteins in each exosome subset reveals that the preferentially packaged PTM proteins in L-Exo, M-Exo, and S-Exo are associated with immune response, biological metabolism, and molecule transport processes, respectively. Our PTM proteomics study based on size-dependent exosome subtypes opens a new avenue for deconstructing the heterogeneity of exosomes.

Manually curated database of exosomal proteins, RNA and lipids. Web based compendium of exosomal cargo. Database catalogs information from both published and unpublished exosomal studies. Mode of exosomal purification and characterization, biophysical and molecular properties are listed.

Proteomics study of human urine exosomes. This data describes the proteomic complement of the human exosomal urine fraction from 10 healthy volunteers (5 male, 5 female) aged 23 to 36 years. 50 µg protein from each sample were fragmented on a 4%/12% SDS-polyacrylamide gel. Following staining, each gel track was separated into 28 equal sections, which were processed individually. Peptides were separated by reverse-phase chromatography (Dionex, Sunnyvale, CA) and LC-MS/MS was performed using an Eksigent NanoLC-1D Plus (Eksigent Technologies, Dublin, CA) HPLC system and an LTQ Orbitrap mass spectrometer (ThermoFisher, Waltham, MA). Peptides from each gel segment were analysed twice: (1) with a dynamic exclusion list and (2) a fixed exclusion list for the abundant protein uromodulin which was superimposed on a dynamic exclusion. MS data were processed using SEQUEST Bioworks Browser (version 3.3.1 SP1, ThermoFisher) to generate MS/MS peak lists. Combined peak list files were submitted to the MASCOT search algorithm (version 2.2.1, Matrix Science, London UK) and searched against the IPI-Human database.

Exosomes transport biologically active cargo (e.g., proteins and microRNA) between cells, including many of the paracrine factors that mediate the beneficial effects associated with stem-cell therapy. Stem cell derived exosomes, in particular mesenchymal stem cells (MSCs), have been shown previously to largely replicate the therapeutic activity associated with the cells themselves, which suggests that exosomes may be a useful cell-free alternative for the treatment of cardiovascular disorders. However, the mechanisms that govern how exosomes home to damaged cells and tissues or the uptake and distribution of exosomal cargo are poorly characterized, because techniques for distinguishing between exosomal proteins and proteins in the targeted tissues are lacking. Here, we report the development of an in-vivo model that enabled the visualization, tracking, and quantification of proteins from systemically administered MSC exosomes. The model uses bioorthogonal chemistry and cell-selective metabolic labeling to incorporate the noncanonical amino acid azidonorleucine (ANL) into the MSC proteome. ANL incorporation is facilitated via expression of a mutant (L274G) methionyl-tRNA-synthetase (MetRS*) and subsequent incubation with ANL-supplemented media; after which ANL can be covalently linked to alkyne-conjugated reagents (e.g., dyes, resins) via click chemistry. Our results demonstrate that when the exosomes produced by ANL-treated, MetRS*-expressing MSCs were systemically administered to mice, the ANL-labeled exosomal proteins could be accurately and reliably identified, isolated, and quantified from a variety of mouse organs, and that myocardial infarction (MI) both increased the abundance of exosomal proteins and redistributed a number of them from the membrane fraction of intact hearts to the cytosol of cells in infarcted hearts. Additionally, we found that Desmoglein-1c is enriched in MSC exosomes and taken up by ischemic myocardium. Collectively, our results indicate that this newly developed bioorthogonal system can provide crucial insights into exosome homing, as well as the uptake and biodistribution of exosomal proteins.

Background: Hepatocellular carcinoma (HCC) is one of the most malignant tumors with a poor prognosis. There is still a lack of effective biomarkers to predict its prognosis. Exosomes participate in intercellular communication and play an important role in the development and progression of cancers.Methods: In this study, two machine learning methods (univariate feature selection and random forest (RF) algorithm) were used to select 13 exosome-related genes (ERGs) and construct an ERG signature. Based on the ERG signature score and ERG signature-related pathway score, a novel RF signature was generated. The expression of BSG and SFN, members of 13 ERGs, was examined using real-time quantitative polymerase chain reaction and immunohistochemistry. Finally, the effects of the inhibition of BSG and SFN on cell proliferation were examined using the cell counting kit-8 (CCK-8) assays.Results: The ERG signature had a good predictive performance, and the ERG score was determined as an independent predictor of HCC overall survival. Our RF signature showed an excellent prognostic ability with the area under the curve (AUC) of 0.845 at 1 year, 0.811 at 2 years, and 0.801 at 3 years in TCGA, which was better than the ERG signature. Notably, the RF signature had a good performance in the prediction of HCC prognosis in patients with the high exosome score and high NK score. Enhanced BSG and SFN levels were found in HCC tissues compared with adjacent normal tissues. The inhibition of BSG and SFN suppressed cell proliferation in Huh7 cells.Conclusion: The RF signature can accurately predict prognosis of HCC patients and has potential clinical value.

Factors determining habitat variability are poorly understood despite possible explanations based on genome and physiology. This is because previous studies only focused on primary measures such as genome size and body size. In this study, we hypothesize that specific gene functions determine habitat variability in order to explore new factors beyond primary measures. We comprehensively evaluate the relationship between gene functions and the climate envelope while statistically controlling for potentially confounding effects by using data on the habitat range, genome, body size and metabolism of various mammals. Our analyses show that the number of proteins and RNAs contained in exosomes is predominantly associated with the climate envelope. This finding indicates the importance of exosomes to habitat range expansion of mammals and provides a new hypothesis for the relationship between the genome and habitat variability.

In the human body, communication between cells takes place in several different ways. Exosomes are a type of extracellular vesicles (30-200 nm in diameter) that also participate in this process. Exosomes can be released from most cell types in the body and exist naturally in different body fluids, such as blood.

In 2007, we showed for the first time that exosomes also transport RNA molecules (both coding and non-coding RNA molecules) between cells (Valadi H. et al. Nature Cell Biology. 2007). The findings describe a new type of 'cell-cell' communication by which different cells send genetic messages to each other by secreting vesicles (exosomes) containing specific RNA molecules.

Our current studies aim to (a) identify cellular actors involved in translocation (packaging) of RNA into exosomes during their biosynthesis, (b) identify the mechanism by which exosomes are taken up by recipient cells/ tissues, and (c) ) discover a method to introduce exogenous/ therapeutic RNA into exosomes, to be used for in vivo transport of therapeutic RNA to different organs.

RNA-binding proteins (RBPs) present in exosomes derived from HTB177 cells (NCI-H460 H460 were identified as described below.

For more detailed description please see Statello L, Maugeri M, Garre E, Nawaz M, Wahlgren J, Papadimitriou A, et al. (2018) (doi: 10.1371/journal.pone.0195969. eCollection 2018). List of the identified proteins can be found in the section 'Data collection' as well as on the journal's website (https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0195969#sec025).

Identification of RNA binding proteins in exosomes and their parent cells: To detect and isolate the RBPs in cells and exosomes, the biotinylated esRNAs, cellular miRNAs, and cellular mRNAs were attached to streptavidin-coated paramagnetic Dynabeads M-280 and were incubated with native protein extracts of exosomes in separate RNA species assays (total exosomal-protein extract + esRNA;, total exosomal-protein extract + cell-mRNA;, total exosomal-protein extract + cell-miRNA). The protein-RNA complexes were eluted from the beads. The RBPs bound to the different RNAs were then loaded onto an SDS-PAGE gel and target bands were excised, trypsinised and analyzed using LC-MS/MS. Samples without RNA were processed in parallel and were used as negative controls to identify proteins that bound non-specifically to the beads.

Neuroblastoma (NB) is the most common extracranial solid tumor during infancy, causing up to 10% of mortality in children. NB shows notable heterogeneity with regard to histology and clinical behavior, ranging from low-risk localized tumors (LR-NB) to high-risk disease (HR-NB), characterized by aggressive metastatic phenotype, resistance to treatment, and fatal relapse occurrence. Risk stratification demands high accuracy, as it will determine the therapeutic treatment. However, the current therapeutic stratification, based on clinical and molecular risk factors, does not allow to discriminate among patients with similar clinical-pathological parameters who receive the same treatment despite showing markedly different clinical courses. The need of novel diagnostic molecular tools in oncology has led to increasing interest in liquid biopsies as a source of biomarkers, as they provide a minimally invasive method. Body fluids are a source of exosomes, nanosized extracellular vesicles that can drive tumor growth and chemoresistance. We previously identified exosomal microRNAs (exo-miRNA) indicative of HR-NB patient sensitivity/resistance to chemotherapy. As exosomes from cancer patients carry proteins that reflect the surface and cytoplasm content of parental cancer cells, including immunosuppressive molecules known to be associated with cancer progression and/or response to therapy, we extended our study to the exosomal proteins (Exo-prot).The purpose of the study is to identify Exo-prot that (i) are specifically expressed in NB patients and (ii) are associated with tumor phenotype and disease stage, in order to improve risk stratification and refine diagnosis.We isolated exosomes from plasma specimens of 24 HR-NB patients and 24 LR-NB patients at diagnosis and of 24 age-matched healthy controls (CTRL). Exo-prot expression was measured by liquid chromatography-mass spectrometry. Missing value distribution and differential expression analysis (performed with two different imputation methods) were applied to identify the most relevant Exo-prot. ROC analysis assessed the diagnostic value of the identified Exo-prot. We demonstrated that NB patients have a different Exo-prot expression profile compared to CTRL. The deregulated Exo-prot in NB specimens act mainly in tumor-associated pathways and build a strictly connected network. Furthermore, HR-NB patients show a different Exo-miR expression profile compared to LR-NB subjects, with the modulation of molecules involved in cell migration, proliferation and metastasis. Importantly, we show that NCAM, NCL, LUM and VASP have a diagnostic value in discriminating NB patients from CTRL; while MYH9, FN1, CALR, AKAP12 and, with a lower performance, LTBP1 can differentiate HR-NB and LR-NB patients with high accuracy. We demonstrated that Exo-prot deregulated in NB vs CTRL subjects and in HR-NB vs LR-NB patients contribute to NB tumor development and to the aggressive metastatic NB phenotype, respectively. We identified Exo-prot with significant diagnostic value for NB patients and able to efficiently identify the HR-NB subset of patients, which can be employed to improve risk stratification. Our results highlight the applicability of Exo-prot evaluation for integrating NB diagnosis and risk assessment.

Exosome Research Market Outlook

The global exosome research market size was valued at approximately USD 150 million in 2023 and is expected to reach around USD 1.3 billion by 2032, growing at an impressive CAGR of 27% during the forecast period. This exponential growth can be attributed to increasing research activities in the field of exosome biology, rising prevalence of chronic diseases such as cancer and neurodegenerative disorders, and advancements in exosome isolation and analysis technologies.

One of the significant growth factors for this market is the burgeoning interest in personalized medicine. Exosomes, which are small extracellular vesicles secreted by various cell types, play a crucial role in cell-to-cell communication and can provide insights into disease diagnostics and therapeutic targets. The growing emphasis on personalized medicine is prompting extensive research on exosomes, given their potential to serve as biomarkers for early disease detection and as vehicles for targeted drug delivery. This shift towards personalized healthcare solutions is expected to drive the demand for exosome research tools and technologies.

Another key factor fueling the growth of the exosome research market is the increasing funding and investments in life sciences research. Governments, academic institutions, and private organizations worldwide are investing heavily in research initiatives to unravel the molecular mechanisms of diseases. Exosomes have emerged as a focal point in these research endeavors due to their role in pathophysiological processes and their potential therapeutic applications. This influx of funding is facilitating the development of advanced exosome research tools, thereby propelling market growth.

The rising prevalence of chronic and infectious diseases is also contributing to the expansion of the exosome research market. Diseases such as cancer, cardiovascular diseases, and neurodegenerative disorders are on the rise globally, and there is a growing need for innovative diagnostic and therapeutic approaches. Exosome research offers promising avenues for understanding disease mechanisms, identifying novel biomarkers, and developing targeted therapies. As the burden of these diseases continues to grow, so does the importance of exosome research in the biomedical field.

Regionally, North America dominates the exosome research market, driven by robust research infrastructure, significant funding for life sciences research, and a high prevalence of chronic diseases. However, Asia Pacific is expected to witness the fastest growth during the forecast period, owing to increasing healthcare expenditure, rising awareness about advanced diagnostic technologies, and expanding research activities in emerging economies such as China and India. Europe also holds a substantial market share, supported by well-established research institutions and active participation in collaborative research projects.

Product Type Analysis

In terms of product types, the exosome research market is segmented into kits & reagents, instruments, software, and services. Kits and reagents constitute a significant share of the market, driven by their extensive use in exosome isolation, characterization, and analysis. The growing demand for high-quality, reliable reagents and kits that facilitate efficient exosome extraction and detection is a major factor contributing to this segment's dominance. Additionally, continuous innovation and development of novel reagents and kits tailored for specific applications are expected to further boost market growth.

The instruments segment is also witnessing substantial growth, fueled by advancements in technologies such as flow cytometry, nanoparticle tracking analysis, and electron microscopy, which are crucial for exosome analysis. The increasing adoption of these advanced instruments in research laboratories and clinical settings is driving the demand for sophisticated exosome research tools. Furthermore, ongoing technological advancements aimed at enhancing the sensitivity, accuracy, and throughput of these instruments are likely to propel the market growth in this segment.

Software solutions play a pivotal role in the exosome research market by enabling efficient data analysis and interpretation. The integration of artificial intelligence and machine learning algorithms in software platforms is enhancing the accuracy and speed of exosome data analysis, thereby facilitating breakthroughs in research. The growing need for robust data management and analysis tools is driving the adoption of s

Exosome Proteomics Service Market Outlook

The global exosome proteomics service market size was valued at approximately USD 250 million in 2023 and is projected to reach around USD 1.1 billion by 2032, growing at a compound annual growth rate (CAGR) of about 18.3% from 2024 to 2032. This burgeoning growth can be attributed to rising demand for precision medicine, expanding research activities in the field of exosome-based diagnostics, and increased investments by pharmaceutical and biotechnology companies.

A significant growth factor driving the exosome proteomics service market is the increasing prevalence of chronic diseases such as cancer, cardiovascular diseases, and neurodegenerative disorders. Exosomes, which are small extracellular vesicles, play a crucial role in intercellular communication and have shown promising potential as biomarkers for early disease detection, prognosis, and therapeutic targets. With the healthcare industry moving towards personalized medicine, the importance of exosome proteomics in understanding disease mechanisms and developing targeted therapies has escalated, thereby fueling market growth.

Another critical factor contributing to market expansion is the advancement in proteomics technologies. Innovations in mass spectrometry and next-generation sequencing have enabled more precise and comprehensive analysis of exosomal proteins. These technological advancements have facilitated high-throughput and high-resolution identification and quantification of exosomal proteins, accelerating the pace of research in this field. Furthermore, the integration of bioinformatics tools and machine learning algorithms in proteomics analysis has enhanced the interpretation of complex data, making it more accessible to researchers and clinicians.

Increased funding and collaborations between academic institutions, research organizations, and industry players are also pivotal in propelling market growth. Governments and private entities are investing heavily in exosome research, recognizing its potential in revolutionizing disease diagnostics and treatment. Collaborative efforts aim to bridge the gap between basic research and clinical application, thereby expediting the translation of exosome-based discoveries into practical healthcare solutions. Additionally, the establishment of dedicated exosome research centers and consortia is fostering a collaborative environment, further driving advancements in this domain.

Regionally, North America leads the market owing to its robust healthcare infrastructure, extensive research and development activities, and the presence of major pharmaceutical and biotechnology companies. Europe follows closely, driven by significant investments in biomedical research and favorable regulatory frameworks. The Asia Pacific region is expected to witness the highest growth rate during the forecast period, fueled by increasing healthcare expenditure, rising awareness about personalized medicine, and growing research initiatives in emerging economies like China and India.

Exosome Technology Services are becoming increasingly pivotal in the landscape of modern healthcare and research. These services encompass a wide range of applications, from the isolation and purification of exosomes to their detailed analysis and functional characterization. As the understanding of exosomes' role in intercellular communication and disease progression deepens, the demand for specialized technology services that can efficiently handle these tasks is on the rise. Companies offering exosome technology services are focusing on developing innovative solutions that cater to the specific needs of researchers and clinicians. These solutions often include advanced isolation techniques, comprehensive proteomics analysis, and the integration of bioinformatics tools to streamline data interpretation. The growth of exosome technology services is further fueled by the increasing interest in personalized medicine and the potential of exosomes as biomarkers and therapeutic agents.

Service Type Analysis

Isolation and Purification

The isolation and purification segment holds a significant share of the exosome proteomics service market. With advancements in isolation techniques such as ultracentrifugation, precipitation, and immunoaffinity capture, the ability to obtain high-purity exosomes has improved considerably. These methods are critical for downstream proteomics analysis, as the quality of iso

Figures and datasets used in the manuscript "Label-Free Identification of Exosomes Using Raman Spectroscopy and Machine Learning". Codes that produce the figures are also included.

The yeast exosome is a conserved multiprotein complex essential for RNA processing and degradation. In this work, we investigated the effects of amino acid substitutions in the exosome subunit Rrp43p on the stability of the complex by comparing the interaction profiles of the complexes purified from the wild type and mutant strains. For that, protein samples were digested with trypsin and the resulting peptides were analyzed by LC-MS/MS (Q-Tof Premier, Waters). The spectra were acquired using software MassLynx v.4.1 and the raw data files were converted to a peak list format (mgf) by the software Mascot Distiller v.2.3.2.0, 2009 (Matrix Science Ldt.) and searched against the yeast database (NCBI- 6702 sequences; 3018299 residues; release data April, 2013) using Mascot engine v.2.3.01 (Matrix Science Ltd.), with carbamidomethylation as fixed modifications, oxidation of methionine as variable modification, one trypsin missed cleavage and a tolerance of 0.1 Da for both precursor and fragment ions. Peptides were considered as unique when it differed in at least 1 amino acid residue. Among these, covalently modified peptides, including N- or C-terminal elongation (i.e. missed cleavages) were counted as unique, but different charge states of the same peptide and modifications were not considered as a criterion to differentiate peptides. Unique peptides with a minimum of five amino acid residues and displaying a significant threshold (p<0.05) in Mascot-based score were considered. The results showed that lower amounts of the exosome subunits are co-purified with the mutant Rrp43p proteins. Additionally, by decreasing the stability of the exosome, other non-specific protein interactions are favored. Therefore, data reported here indicate that complexes containing a mutant Rrp43p exhibit decreased stability and provide information on additional protein interactions.

Background: Hepatocellular carcinoma (HCC) is one of the fifty most common cancers globally, having a high mortality rate being the second most common cause of cancer-related deaths. However, little attention has been paid to the involvement of exosomes and ceRNA in HCC.Method: The study aimed to explore exosome data from exoRBase database and a free online database to estimate possible binding miRNA from mRNA, lncRNA, and circRNA and discover useful exosome biomarkers for HCC therapy.Results: The results indicated that a total of 159 mRNAs, 60 lncRNAs, and 13 circRNAs were differentially expressed, with HIST2H3C exhibiting the highest log2FC change, CTD-2031P19 exhibiting the most relevant lncRNA, and CTD-2031P19 exhibiting the most relevant lncRNA. MARCH8, SH3PXD2A, has-circ-0014088, hsa-miR-186-5p, and hsa-miR-613 were identified as hub biomarkers used by Cytoscape. According to the KEGG pathway analysis results, the differentially expressed proteins were primarily enriched in the MAPK signaling network, central carbon metabolism in cancer, the glucagon signaling pathway, glutamatergic synapse, and spliceosome. Furthermore, immunohistochemical images from the Human Protein Atlas (HPA) online tool were used to directly evaluate the protein expression of SMARCA5, CDC42, and UBC between normal and cancer tissues, and the results showed that these three gene expressions were significantly higher in tumor tissues.Conclusion: This study discovered atypical signature exosomes for HCC prognostic prediction based on an online database. The signals could mimic exosome microenvironmental disorders providing potential biomarkers for exosome treatment.

Exosome Diagnostic and Therapeutic Market Outlook

The global exosome diagnostic and therapeutic market size was valued at USD 300 million in 2023 and is forecasted to reach USD 1.5 billion by 2032, growing at a compound annual growth rate (CAGR) of 20%. This impressive growth is driven by the increasing adoption of exosome-based diagnostics and therapeutics in various medical fields such as oncology, neurology, and cardiology. The rise in personalized medicine, coupled with advancements in exosome isolation and analysis technologies, are primary factors propelling the market expansion.

The rising prevalence of chronic and infectious diseases is a significant growth factor for the exosome diagnostic and therapeutic market. Chronic diseases such as cancer, cardiovascular diseases, and neurodegenerative disorders require early and accurate diagnosis for effective treatment. Exosomes, being small extracellular vesicles involved in intercellular communication, play a crucial role in disease progression and can serve as biomarkers for these conditions. The increasing incidence of these diseases globally underscores the demand for advanced diagnostic tools, driving the market forward.

Technological advancements are another key driver for the market. Innovations in exosome isolation and characterization techniques have enhanced the accuracy and efficiency of exosome-based diagnostics. For example, the development of microfluidic and nanotechnology-based platforms has revolutionized exosome analysis, enabling high-throughput and sensitive detection of exosomal biomarkers. These advancements not only improve diagnostic capabilities but also facilitate the development of exosome-based therapeutics, thereby expanding the market potential.

The growing emphasis on personalized medicine is significantly boosting the exosome diagnostic and therapeutic market. Personalized medicine involves tailoring medical treatment to the individual characteristics of each patient, which requires precise and detailed diagnostic information. Exosomes, with their ability to reflect the molecular composition of their parent cells, provide valuable insights into the patient's condition. This capability makes exosome-based diagnostics particularly attractive for personalized treatment approaches, further driving market growth.

Regional factors also play a crucial role in the market dynamics. North America, with its advanced healthcare infrastructure and significant investment in research and development, dominates the exosome diagnostic and therapeutic market. However, the Asia Pacific region is expected to witness the highest growth rate due to increasing healthcare expenditure, rising awareness about advanced diagnostics, and the growing prevalence of chronic diseases. The proactive efforts by governments and private sectors in these regions to improve healthcare outcomes will continue to propel market growth.

Product Type Analysis

The exosome diagnostic and therapeutic market can be segmented into instruments, reagents, and software. Instruments, which include devices used for the isolation and analysis of exosomes, form a critical component of the market. The demand for advanced and efficient instruments is driven by the need for precise exosome characterization, which is essential for accurate diagnosis and therapeutic development. Innovations in instrument technology, such as the integration of microfluidics and nanotechnology, have significantly enhanced the efficiency and accuracy of exosome isolation and analysis, driving market growth.

Reagents constitute another vital segment of the market. These include the various chemicals and biological substances used in the processes of exosome isolation, purification, and analysis. The continuous development of specialized reagents that enhance the sensitivity and specificity of exosome detection is crucial for the advancement of exosome-based diagnostics and therapeutics. The increasing demand for high-quality reagents that can provide reliable and reproducible results is a significant driver for this market segment.

Software solutions play a supportive yet crucial role in the exosome diagnostic and therapeutic market. These software tools are used to analyze and interpret the complex data generated during exosome research and diagnostics. The integration of advanced data analytics, artificial intelligence, and machine learning into these software solutions has revolutionized exosome research by enabling more accurate and comprehensive data interpretation. The growing need for sophisticated software t

During the last decade, skeletal muscle-secreted proteins have been identified with important roles in intercellular communications. To investigate whether muscle-derived exosomes participate in this molecular dialog, we determined and compared the protein contents of the exosome-like vesicles (ELVs) released from C2C12 murine myoblasts during proliferation (ELV-MB), and after differentiation into myotubes (ELV-MT). Using a proteomic approach combined with electron microscopy, western-blot and bioinformatic analyses, we compared the protein repertoires within ELV-MB and ELV-MT. RAW files were processed using MaxQuant [28] version 1.3.0.3. Spectra were searched against the Uniprot database (August 2012 version, Mus musculus taxonomy 10090, 86644 sequences, Bos taurus taxonomy 9913, 34280 sequences and Equus caballus taxonomy 9796, 24299 sequences) and the frequently observed contaminants database (notably containing protein sequences from serum proteins) embedded in MaxQuant. Trypsin was chosen as the enzyme and 2 missed cleavages were allowed. Precursor mass error tolerances were set respectively at 20 ppm and 6 ppm for first and main searches. Fragment mass error tolerance was set to 0.5 Da. Peptide modifications allowed during the search were: trioxidation (C, fixed), acetyl (N-ter, variable), dioxidation (M, variable), oxidation (M, variable) and deamidation (NQ, variable). Minimum peptide length was set to 7 amino acids. Minimum number of peptides, razor+unique peptides and unique peptides were set respectively to 2, 2 and1. Maximum false discovery rates - calculated by employing a reverse database strategy - were set to 0.01 at peptide and protein levels.

Exosomes, a key element of the central nervous system microenvironment, mediate intercellular communication via horizontally transferring bioactive molecules. Emerging evidence has implicated exosomes in the regulation of neurogenesis. Recently, we compared the neurogenic potential of exosomes released from primary mouse embryonic neural stem cells (NSCs) and astrocyte-reprogrammed NSCs, and observed diverse neurogenic potential of those two exosome populations in vitro. However, the roles of NSC-derived exosomes on NSC differentiation and the underlying mechanisms remain largely unknown. In this study, we firstly demonstrated that NSC-derived exosomes facilitate the differentiation of NSCs and the maturation of both neuronal and glial cells in defined conditions. We then identified miR-9, a pro-neural miRNA, as the most abundantly expressed miRNA in NSC-derived exosomes. The silencing of miR-9 in exosomes abrogates the positive effects of NSC-derived exosomes on the differentiation of NSCs. We further identified Hes1 as miR-9 downstream target, as the transfection of Hes1 siRNA restored the differentiation promoting potential of NSC-derived exosomes after knocking down exosomal miR-9. Thus, our data indicate that NSC-derived exosomes facilitate the differentiation of NSCs via transferring miR-9, which sheds light on the development of cell-free therapeutic strategies for treating neurodegeneration.

The RNA exosome is a key 3'-5' exoribonuclease with an evolutionarily conserved structure and function. Its cytosolic functions require the co-factors SKI7 and the Ski complex. Here we demonstrate by co-purification experiments that the ARM-repeat protein RESURRECTION1 (RST1) and RST1 INTERACTING PROTEIN (RIPR) connect the cytosolic Arabidopsis RNA exosome to the Ski complex. rst1 and ripr mutants accumulate RNA quality control siRNAs (rqc-siRNAs) produced by the post-transcriptional gene silencing (PTGS) machinery when mRNA degradation is compromised. The small RNA populations observed in rst1 and ripr mutants are also detected in mutants lacking the RRP45B/CER7 core exosome subunit. Thus, molecular and genetic evidence supports a physical and functional link between RST1, RIPR and the RNA exosome. Our data reveal the existence of additional cytosolic exosome co-factors besides the known Ski subunits. RST1 is not restricted to plants, as homologues with a similar domain architecture but unknown function exist in animals, including humans.

This repository contains the modeling scripts, the ensemble of models, and the results of the analysis for the modeling of the S.cerevisiae exosome complex (named exo10, comprising of Rrp40, Rrp4, Csl4, Rrp45, Rrp46, Rrp42, Rrp43, Mtr3, Ski6 and Rrp44), in presence of Ski7 (exo10+Ski7 below) or Rrp6 (exo10+Rrp6 below) proteins. The modeling is performed based on cross-link Mass-Spectrometry data, crystallographic structures, and comparative models.

For more information about how to reproduce this modeling, see https://salilab.org/exosome or the README file.

Heavy tick burden on beef cattle account for huge economic losses globally, with an estimated value of US$22-30 billion per annum. In Australia, ticks cost the northern beef industry approximately A$170-200 million. Methods to evaluate and predict tick resistance would therefore be of great value to the global cattle trade. Exosomes (EX) are small extracellular vesicles (EVs) of ~30-150nm diameter and have gained popularity for their diagnostic and prognostic potential. EX contain, among other biomolecules, various types of RNA including micro-RNA (miRNA) and long noncoding RNA (lncRNA). MiRNA specifically have been validated as therapeutic biomarkers as they perform regulatory functions at the post-transcriptional level and are differentially expressed between divergent groups.

The objective of the present study was to evaluate the miRNA profiles of EV and fractionated exosomal samples of high and low tick-resistant beef cattle to highlight potential miRNA biomarkers of tick resistance. Cows (n = 3/group) were classified into high or low tick resistant groups according to a novel scoring system. EVs and EX were isolated and fractionated from the blood plasma of high and low tick resistant cattle using established isolation and enrichment protocols. The resultant EX and non-EX samples were processed for next generation miRNA sequencing. Offspring of the cows in each high and low tick resistant group underwent the same processing for blood plasma EX, non-EX and miRNA analysis to evaluate the heritability of miRNA associated with tick resistance.

A total of 2631 miRNAs were identified in EX and non-EX fractionated samples from high and low tick-resistant beef cattle. MiR-449a was highly expressed in maternal high tick-resistant EX samples. Of these, 174 were novel miRNAs, and 10 were differentially expressed (DE) (FDR < 0.05). These 10 DE miRNAs were also present in EVs, and three miRNAs were highly expressed: miR-2419-3p, miR-7861-3p and miR-2372-5p. Although 196 novel miRNAs were identified in fractionated samples of offspring, no miRNA were differentially expressed in these animals.

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Exosome Diagnostics And Therapeutics Market Size 2025-2029

The exosome diagnostics and therapeutics market size is forecast to increase by USD 1.01 billion, at a CAGR of 26.5% between 2024 and 2029.

The market is experiencing significant growth, driven by the advancements in exosome research and technology. Exosomes, small extracellular vesicles, carry bioactive molecules from cells, making them promising diagnostic and therapeutic tools. The collection of exosomes is becoming more sophisticated, with methods such as ultracentrifugation, size exclusion chromatography, and immunoaffinity capture gaining popularity. However, this market faces a substantial challenge in the form of stringent regulatory approval processes for product launches. The regulatory bodies require extensive clinical trials and rigorous testing to ensure the safety and efficacy of exosome-based diagnostics and therapeutics.
This not only increases the time and cost of bringing these products to market but also poses a significant barrier for new entrants. Companies seeking to capitalize on the opportunities in this market must navigate these challenges effectively by investing in robust research and development programs, collaborating with regulatory agencies, and building strong partnerships with key industry players.

What will be the Size of the Exosome Diagnostics And Therapeutics Market during the forecast period?

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The market continues to evolve, driven by advances in technology and research. Exosomes, small extracellular vesicles, play a crucial role in intercellular communication and have emerged as potential diagnostic and therapeutic agents. The market encompasses various sectors, including safety, industry standards, exosome-mediated drug delivery, intellectual property, therapeutics, cancer therapy, regenerative medicine, biocompatibility, RNA sequencing, personalized medicine, gene therapy, characterization, tracking, and targeted drug delivery. Exosome safety and industry standards are paramount, with ongoing efforts to ensure consistency and reliability in production and application. Exosome-mediated drug delivery offers a promising avenue for overcoming challenges in traditional drug delivery methods, while intellectual property protections shape the competitive landscape.

Exosome therapeutics, particularly in cancer and regenerative medicine, are under intensive investigation. Biocompatibility, RNA sequencing, and personalized medicine are key areas of focus for improving efficacy and precision. Exosome-mediated gene therapy holds potential for revolutionary treatments, while characterization and tracking methods enable a better understanding of their role in cell signaling and imaging techniques. Exosome manufacturing, liquid biopsy, data analysis, clinical trials, engineering, microfluidic devices, proteomics, nanomaterials, profiling, diagnostic panels, efficacy, and immunotherapy are all integral components of this dynamic market. The regulatory landscape continues to unfold, shaping the future of exosome-based applications.

How is this Exosome Diagnostics And Therapeutics Industry segmented?

The exosome diagnostics and therapeutics industry research report provides comprehensive data (region-wise segment analysis), with forecasts and estimates in 'USD million' for the period 2025-2029, as well as historical data from 2019-2023 for the following segments.

Application

  Diagnostic
  Therapeutic


End-user

  Research and academic institutes
  Pharmaceutical and biotechnology companies
  Commercial
  Hospitals and Clinics
  Diagnostic Centers
  Cancer Institutes
  Other Healthcare Providers


Product Type

  Instruments
  Reagents/Kits
  Software


Source

  Stem Cells
  Blood
  Urine


Technology

  Ultracentrifugation
  Flow Cytometry


Geography

  North America

    US
    Canada


  Europe

    France
    Germany
    Italy
    UK


  Middle East and Africa

    UAE


  APAC

    China
    India
    Japan
    South Korea


  South America

    Brazil


  Rest of World (ROW)

By Application Insights

The diagnostic segment is estimated to witness significant growth during the forecast period.

Exosomes, small extracellular vesicles, play a significant role in various physiological and pathological processes, including immunological responses, cancer, cardiovascular disease, and abnormal pregnancies. Early detection and precise diagnosis are crucial for patients with malignancies or precancerous lesions, and non-invasive liquid biopsy using exosomes demonstrates substantial benefits. Exosomes can be isolated from various body fluids, ensuring stability and preserving their unique biomolecular cargo, which includes proteins, lipids, DNA, and RNA. Exosome research tools and technologies, such as mass spectrometry, bioinformatics, and nanomaterials, facilitate characterization, trac