Exosomal Cargo Research Articles

MicroRNA and Exosome in Retinal-related Diseases: Their Roles in the Pathogenesis and Diagnosis.

The precise and exquisite architecture of the retina is directly related to vision. Therefore, any mechanisms associated with disruption of retinal structure could affect the quality of vision. A large number of studies indicated that several cellular and molecular processes are involved in retina pathogenesis. Among different risk factors reported as important players in retina diseases, deregulation of epigenetic contributors has critical roles in the pathogenesis of these diseases. MicroRNAs (miRNAs) are a type of small non-coding RNAs that are involved in various signaling pathways involved in retina diseases. These molecules exert their function by targeting a sequence of cellular and molecular signals. Long-non coding RNAs (lncRNAs) and circular RNAs are other non-coding RNAs, which can exert their regulatory roles via miRNA sponging. In this regard, it has been showed that miRNA sponging could modulate a variety of pathways in retinal diseases. Besides miRNAs, exosomes are other players in the pathogenesis of retinal diseases. Exosomes are biological vectors that could carry their cargos to recipient cells. The cargos of exosomes (i.e., proteins, lncRNAs, miRNAs, and fragments of DNA) change behaviors of host cells. Here, we summarized the roles of miRNAs, miRNAs sponging and exosomes in the pathogenesis of retinal diseases.

Role of Exosomes in Immune Microenvironment of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Since most patients with HCC are diagnosed at the intermediate or advanced stage and because HCC has a high incidence of metastasis and recurrence, it is one of the leading causes of cancer death. Exosomes are a subtype of extracellular vesicles and are typically 30–150 nm in diameter. Originating from endosomes, they can be secreted by almost all living cells. They are widely present in various body fluids and serve as an important medium for the interactions between cells. A series of studies have revealed that exosomes-mediated intercellular transfer of proteins, nucleic acids, and metabolites plays a crucial role in the initiation and progression of HCC, hypoxia and angiogenesis, chemotherapy sensitivity, and cell death mode and regulates the immune microenvironment. In this paper, we reviewed the recent researches on the multiple roles of tumor-associated exosomes in the progression of HCC. We laid particular focus on those researches that reveal how exosomes regulate the tumor immune microenvironment (TIME) and how exosomal cargos affect the progression of HCC. Besides, we emphasize some prospective directions to achieve a more accurate and complete analysis of the HCC immune microenvironment.

P034 DISRUPTive liquid biopsies in Inflammatory Bowel Disease (DISRUPT-IBD): Release of exosomal and molecular tissue signals by transabdominal ultrasound?

Abstract Background A major drawback in diagnosis and monitoring of IBD are insufficient biomarkers that do not correlate well with tissue disease activity. Inflammation and cellular stress lead to an increased release of exosomes (Lipinski et al, 2019, EMBO J) carrying inflammatory signal proteins as cargo (Wozniak et al, 2020, J Cell Biol). Interestingly, colorectal cancer cells strongly release tumor markers after stimulation by sonography waves, probably through the disruptive energy of standard ultrasound (D’Souza et al, 2009, PNAS). We thus hypothesize that application of ultrasound waves on inflamed intestinal tissue in active IBD induces the release of tissue-specific exosomes that can be detected in the peripheral blood and used as novel biomarkers. Methods 26 patients with different degrees of disease activity and various ongoing therapies with IBD were included in a pilot trial. Serum was taken before and 30 minutes after diagnostic transabdominal ultrasound. Serum exosomes were precipitated (using ExoQuick) and exosomal (exo-)miRNA were isolated for miRNA sequencing using SeraMir protocol. Exosomal proteins were isolated for quantification of inflammatory markers (as exosomal cargo). Results We found a correlation between exo-miRNA concentration and disease severity, determined by clinical assessment scores and sonographic findings. Exo-miRNA sequencing revealed a select few miRNAs to be induced by sonography. However, the overall composition of annotated miRNA transcripts did not separate samples according to sampling timepoints. Among these “inducible” exo-miRNA, we found hsa-miR-942, which is involved in cell cycle and Wnt signaling in intestinal epithelial cells, to be significantly induced in higher grade intestinal inflammation. The exosomal protein concentrations did not correlate with disease severity at baseline, but were increased after sonography in severe intestinal inflammation. We did not find markers of the inflammasome apparatus as inducible exosomal cargos. Conclusion Sonography-induced exosomal markers, e.g., exo-miRNAs, could become novel biomarkers for intestinal inflammation in IBD. Further exploration of the functional role of inducible biomarkers and continued investigation of exosomal miRNA and protein profiling will be performed.

Microglia-Derived Exosomal microRNA-151-3p Enhances Functional Healing After Spinal Cord Injury by Attenuating Neuronal Apoptosis via Regulating the p53/p21/CDK1 Signaling Pathway.

Spinal cord injury (SCI) is a catastrophic event mainly involving neuronal apoptosis and axonal disruption, and it causes severe motor and sensory deficits. Due to the complicated pathological process of SCI, there is currently still a lack of effective treatment for SCI. Microglia, a type of immune cell residing in the central nervous system (CNS), need to respond to various stimuli to protect neuronal cells from death. It was also reported that microRNAs (miRNAs) had been identified in microglia-derived exosomes that can be taken up by neurons. However, the kinds of miRNAs in exosome cargo derived from microglia and the underlying mechanisms by which they contribute to neuroprotection after SCI remain unknown. In the present study, a contusive SCI mouse model and in vitro experiments were applied to explore the therapeutic effects of microglia-derived exosomes on neuronal apoptosis, axonal regrowth, and functional recovery after SCI. Then, miRNA analysis, rescue experiments, and luciferase activity assays for target genes were performed to confirm the role and underlying mechanism of microglia-derived exosomal miRNAs in SCI. We revealed that microglia-derived exosomes could promote neurological functional recovery by suppressing neuronal apoptosis and promoting axonal regrowth both in vivo and in vitro. MicroRNA-151-3p is abundant in microglia-derived exosomes and is necessary for mediating the neuroprotective effect of microglia-derived exosomes for SCI repair. Luciferase activity assays reported that P53 was the target gene for miR-151-3p and that p53/p21/CDK1 signaling cascades may be involved in the modulation of neuronal apoptosis and axonal regrowth by microglia-derived exosomal microRNA-151-3p. In conclusion, our data demonstrated that microglia-derived exosomes (microglia-Exos) might be a promising, cell-free approach for the treatment of SCI. MicroRNA-151-3p is the key molecule in microglia-derived exosomes that mediates the neuroprotective effects of SCI treatments.

Cancer-Associated Fibroblasts Influence the Biological Properties of Malignant Tumours via Paracrine Secretion and Exosome Production.

Cancer-associated fibroblasts (CAFs) are an essential component of the tumour microenvironment. They represent a heterogeneous group of cells that are under the control of cancer cells and can reversely influence the cancer cell population. They affect the cancer cell differentiation status, and the migration and formation of metastases. This is achieved through the production of the extracellular matrix and numerous bioactive factors. IL-6 seems to play the central role in the communication of noncancerous and cancer cells in the tumour. This review outlines the role of exosomes in cancer cells and cancer-associated fibroblasts. Available data on the exosomal cargo, which can significantly intensify interactions in the tumour, are summarised. The role of exosomes as mediators of the dialogue between cancer cells and cancer-associated fibroblasts is discussed together with their therapeutic relevance. The functional unity of the paracrine- and exosome-mediated communication of cancer cells with the tumour microenvironment represented by CAFs is worthy of attention.

Oncogenic Role of Exosomal Circular and Long Noncoding RNAs in Gastrointestinal Cancers.

Circular RNAs (circRNAs) and long noncoding RNAs (lncRNAs) are differentially expressed in gastrointestinal cancers. These noncoding RNAs (ncRNAs) regulate a variety of cellular activities by physically interacting with microRNAs and proteins and altering their activity. It has also been suggested that exosomes encapsulate circRNAs and lncRNAs in cancer cells. Exosomes are then discharged into the extracellular environment, where they are taken up by other cells. As a result, exosomal ncRNA cargo is critical for cell–cell communication within the cancer microenvironment. Exosomal ncRNAs can regulate a range of events, such as angiogenesis, metastasis, immune evasion, drug resistance, and epithelial-to-mesenchymal transition. To set the groundwork for developing novel therapeutic strategies against gastrointestinal malignancies, a thorough understanding of circRNAs and lncRNAs is required. In this review, we discuss the function and intrinsic features of oncogenic circRNAs and lncRNAs that are enriched within exosomes.

Modulation of Dendritic Cells by Microbiota Extracellular Vesicles Influences the Cytokine Profile and Exosome Cargo.

Gut bacteria release extracellular vesicles (BEVs) as an intercellular communication mechanism that primes the host innate immune system. BEVs from E. coli activate dendritic cells (DCs) and subsequent T-cell responses in a strain-specific manner. The specific immunomodulatory effects were, in part, mediated by differential regulation of miRNAs. This study aimed to deepen understanding of the mechanisms of BEVs to drive specific immune responses by analyzing their impact on DC-secreted cytokines and exosomes. DCs were challenged with BEVs from probiotic and commensal E. coli strains. The ability of DC-secreted factors to activate T-cell responses was assessed by cytokine quantification in indirect DCs/naïve CD4+ T-cells co-cultures on Transwell supports. DC-exosomes were characterized in terms of costimulatory molecules and miRNAs cargo. In the absence of direct cellular contacts, DC-secreted factors triggered secretion of effector cytokines by T-cells with the same trend as direct DC/T-cell co-cultures. The main differences between the strains influenced the production of Th1- and Treg-specific cytokines. Exosomes released by BEV-activated DCs were enriched in surface proteins involved in antigen presentation and T-cell activation, but differed in the content of immune-related miRNA, depending on the origin of the BEVs. These differences were consistent with the derived immune responses.

The emerging roles of exosomal long non-coding RNAs in bladder cancer.

Extracellular vesicles (EVs), especially exosomes, have been reported to play essential roles as extracellular messengers by transporting goods in various diseases, while their potential roles in bladder cancer (BC) still remain to be further studied. BC exhibits a high degree of chemoresistance and metastatic ability, which may be affected by cancer‐derived exosomes that carry proteins, lipids and RNA. To date, the most studied exosomal molecular cargo is long non‐coding RNA (lncRNA). Although there is increasing interest in its role and function, there is relatively little knowledge about it compared with other RNA transcripts. Nevertheless, in the past ten years, we have witnessed increasing interest in the role and function of lncRNA. For example, lncRNAs have been studied as potential biomarkers for the diagnosis of BC. They may play a role as a therapeutic target in precision medicine, but they may also be directly involved in the characteristics of tumour progression, such as metastasis, epithelial‐mesenchymal transition and drug resistance. Cancer cells are on chemotherapy acting. The function of lncRNA in various cancer exosomes has not yet been determined. In this review, we summarize the current studies about the prominent roles of exosomal lncRNAs in genome integrity, BC progression and carcinogenic features.

Exosomes and the extracellular matrix: a dynamic interplay in cancer progression.

Exosomes are a subtype of extracellular vesicles (EVs) composed of a lipid bilayer, which carry various cargoes such as nucleic acids, proteins, and bioactive lipids. Cancer cells release exosomes to promote cell communication and interaction with the extracellular matrix (ECM). ECM regulates the secretion and uptake of exosomes. Moreover, the cargo of exosomes can control ECM remodeling, thus affecting cancer progression. Aside from the rearrangement of ECM, exosomal cargo also modulates different signaling pathways that maintain homeostasis and play a major role in tumor growth and immune evasion in the tumor microenvironment (TME). Exosomes are now widely recognized as circulating biomarkers for diagnosis and prognosis. Their role in cancer initiation, progression, and chemoresistance is becoming increasingly clear from preclinical and clinical investigations, thereby gaining interest for their potential use as cancer diagnostics tools, but also for the development of future innovative cancer therapeutics. In this mini review we outline and discuss the correlation between exosomes, TME and cancer progression, while focusing on the potential role of exosomes as diagnostic and prognostic biomarkers, as well as therapeutic vehicles for drug delivery.

Emerging role of exosomes as biomarkers in cancer treatment and diagnosis.

Cancer is a leading cause of death worldwide and cancer incidence and mortality are rapidly growing. These massive amounts of cancer patients require rapid diagnosis and efficient treatment strategies. However, the currently utilized methods are invasive and cost-effective. Recently, the effective roles of exosomes as promising diagnostic, prognostic, and predictive biomarkers have been revealed. Exosomes are membrane-bound extracellular vesicles containing RNAs, DNAs, and proteins, and are present in a wide array of body fluids. Exosomal cargos have shown the potential to detect various types of cancers at early stages with high sensitivity and specificity. They can also delivery therapeutic agents efficiently. In this article, an overview of recent advances in the research of exosomal biomarkers and their applications in cancer diagnosis and treatment has been provided. Furthermore, the advantages and challenges of exosomes as liquid biopsy targets are discussed and the clinical implications of using exosomal miRNAs have been revealed.

MicroRNA-Enriched Exosomes from Different Sources of Mesenchymal Stem Cells Can Differentially Modulate Functions of Immune Cells and Neurogenesis.

Adult Mesenchymal stem cells-derived exosomes carry several biologically active molecules that play prominent roles in controlling disease manifestations. The content of these exosomes, their functions, and effect on the immune cells may differ depending on their tissue sources. Therefore, in this study, we purified the exosomes from three different sources and, using the RNA-Seq approach, highly abundant microRNAs were identified and compared between exosomes and parental cells. The effects of exosomes on different immune cells were studied in vitro by incubating exosomes with PBMC and neutrophils and assessing their functions. The expression levels of several miRNAs varied within the different MSCs and exosomes. Additionally, the expression profile of most of the miRNAs was not similar to that of their respective sources. Exosomes isolated from different sources had different abilities to induce the process of neurogenesis and angiogenesis. Moreover, these exosomes demonstrated their varying effect on PBMC proliferation, neutrophil survival, and NET formation, highlighting their versatility and broad interaction with immune cells. The knowledge gained from this study will improve our understanding of the miRNA landscape of exosomes from hMSCs and provide a resource for further improving our understanding of exosome cargo and their interaction with immune cells.

Advances on biological functions of exosomal non-coding RNAs in osteoarthritis.

Exosomes can be secreted by various cells and function as intercellular communication vehicles by delivering specific cargoes from the donor cells to the recipient cells through their paracrine activity. Recently, an increasing number of studies have shown that non-coding RNAs (ncRNAs) could be entrapped in and transferred between cartilage-related cells as exosomal cargoes to modulate the expression of various target genes by regulation at post-transcriptional and post-translational levels. They are mainly comprised of microRNAs, long non-coding RNAs, and circular RNAs. Articular cartilage degeneration is one of the main pathological features of osteoarthritis. Exosomal ncRNAs are involved in pathological processes of osteoarthritis, such as proliferation, migration, chondrogenesis, chondrocyte differentiation induction, extracellular matrix formation, apoptosis, and inflammation. In this review, we summarize the biological functions of exosomal ncRNAs in cartilage homeostasis and osteoarthritis progression and discuss the perspectives and challenges of exosomal ncRNAs application for osteoarthritis patients in the future. Exosomal ncRNA has an important regulatory role in the pathogenesis of osteoarthritis, but more evidence is needed for clinical application.

Diabetes mellitus contribution to the remodeling of the tumor microenvironment in gastric cancer.

Compelling pieces of evidence derived from both clinical and experimental research has demonstrated the crucial contribution of diabetes mellitus (DM) as a risk factor associated with increased cancer incidence and mortality in many human neoplasms, including gastric cancer (GC). DM is considered a systemic inflammatory disease and therefore, this inflammatory status may have profound effects on the tumor microenvironment (TME), particularly by driving many molecular mechanisms to generate a more aggressive TME. DM is an active driver in the modification of the behavior of many cell components of the TME as well as altering the mechanical properties of the extracellular matrix (ECM), leading to an increased ECM stiffening. Additionally, DM can alter many cellular signaling mechanisms and thus favoring tumor growth, invasion, and metastatic potential, as well as key elements in regulating cellular functions and cross-talks, such as the microRNAs network, the production, and cargo of exosomes, the metabolism of cell stroma and resistance to hypoxia. In the present review, we intend to highlight the mechanistic contributions of DM to the remodeling of TME in GC.

Regeneration and Diagnosis of Kidney Disease Using Exosomes

: A growing global prevalence of acute kidney injury (AKI) and chronic kidney disease (CKD), high costs of kidney transplantation, a shortage of kidney donors, and low survival rate after dialysis have popularized mesenchymal stem cell (MSC) therapy via transplantation. However, the risks of tumorigenesis, immune rejection, pathogen transmission, loss of differentiation, and morphological changes after long-term culture have prompted researchers to develop a safer and more effective therapy method. Therefore, cell-free approaches have been developed to reduce the risks associated with stem cell-based therapies. In cell-free therapy of AKI and CKD, MSC-derived extracellular vesicles, with nanometer sizes, are used, called exosomes. Exosomes have a lipid bilayer membrane with various genes, microRNAs, and proteins for kidney repair. As known, MSC-derived exosomes have improved the kidney regeneration process for various reasons, such as increased safety and reduced inflammation, immune rejection, and tumorigenesis. With the advancement of exosome isolation techniques, the possibility of using biologically active molecules for renal injury prediction and diagnosis has emerged. The use of urinary exosomes in AKI and CKD diagnosis is based on changes in the expression of specific molecule cargos of exosomes. This review article summarizes the diagnosis and therapeutic applications of exosomes in AKI and CKD.

Identification of state‐specific proteomic characteristics of microglia‐derived exosomes

AbstractBackgroundAlzheimer’s disease (AD) is the most common neurodegenerative disorder defined by progressive pathological protein aggregation (amyloid‐beta and tau) and deterioration of cognitive function. Microglia‐mediated neuroinflammation is a key pathological component of AD; however, there are critical gaps in our understanding of how microglia perpetuate AD pathology. One proposed mechanism of microglia‐mediated neuroinflammation and neurodegeneration is exosome release because of their critical role in the transport of macromolecules between cells to facilitate intercellular communication. Thus, it is possible that microglia‐derived exosomes transfer pathogenic cargo which could perpetuate AD pathology. The proteomic profiles and influence of different microglia‐derived exosomal populations on AD pathology remain unknown. We hypothesize that different microglia states determine the molecular composition of exosomes.MethodWe treated a murine microglia cell line, BV2 cells, with various cytokines to polarize them and collect their exosomes for downstream mass spectrometry (MS) analyses. Three groups of BV2 cells (n=4/group) were treated with either lipopolysaccharide (LPS) to polarize to a pro‐inflammatory state, interleukin 10 (IL‐10) to polarize to an anti‐inflammatory state, or transforming growth factor beta (TGF‐β) to polarize to a homeostatic state. Untreated BV2 cells served as a control group. Following 72 hours of treatment, BV2 cells were lysed and cell culture media was collected for exosome isolation.ResultTransmission electron microscopy images and western blotting for exosomal marker, CD9, confirmed exosome purification by our isolation method. In MS studies, we identified 533 proteins in exosome fractions and 1,866 proteins in BV2 cell proteomes. We found that known exosome related proteins, Sdcbp and Igsf8, were significantly increased in the exosomal proteome compared to the whole cell proteome. We identified proteins that are differentially expressed across polarization with unique proteins increased in exosomes derived from LPS, IL‐10, and TGF‐β treated BV2 cells. Validation studies of these top hits are ongoing, and studies are underway to replicate these findings in primary microglia.ConclusionOur results indicate that exosomes derived from microglia adopt distinct state‐associated protein profiles which may have differential effects on other cell types. This work will guide future studies concerning the role of exosomal cargo in perpetuating AD pathology.

Development of an exosomal gene signature to detect residual disease in dogs with osteosarcoma using a novel xenograft platform and machine learning

AbstractOsteosarcoma has a guarded prognosis. A major hurdle in developing more effective osteosarcoma therapies is the lack of disease-specific biomarkers to predict risk, prognosis, or therapeutic response. Exosomes are secreted extracellular microvesicles emerging as powerful diagnostic tools. However, their clinical application is precluded by challenges in identifying disease-associated cargo from the vastly larger background of normal exosome cargo. We developed a method using canine osteosarcoma in mouse xenografts to distinguish tumor-derived from host-response exosomal messenger RNAs (mRNAs). The model allows for the identification of canine osteosarcoma-specific gene signatures by RNA sequencing and a species-differentiating bioinformatics pipeline. An osteosarcoma-associated signature consisting of five gene transcripts (SKA2, NEU1, PAF1, PSMG2, and NOB1) was validated in dogs with spontaneous osteosarcoma by real-time quantitative reverse transcription PCR (qRT-PCR), while a machine learning model assigned dogs into healthy or disease groups. Serum/plasma exosomes were isolated from 53 dogs in distinct clinical groups (“healthy”, “osteosarcoma”, “other bone tumor”, or “non-neoplastic disease”). Pre-treatment samples from osteosarcoma cases were used as the training set, and a validation set from post-treatment samples was used for testing, classifying as “osteosarcoma detected” or “osteosarcoma-NOT detected”. Dogs in a validation set whose post-treatment samples were classified as “osteosarcoma-NOT detected” had longer remissions, up to 15 months after treatment. In conclusion, we identified a gene signature predictive of molecular remissions with potential applications in the early detection and minimal residual disease settings. These results provide proof of concept for our discovery platform and its utilization in future studies to inform cancer risk, diagnosis, prognosis, and therapeutic response.

Three-dimensional printing of bioceramic-induced macrophage exosomes: immunomodulation and osteogenesis/angiogenesis

Exosomes have attracted increasing attention in tissue regeneration and repair due to their roles in intercellular communication. Developing a customized delivery system is key to exosome-based regenerative therapeutics. Bioceramics play an important role in the immunomodulation of macrophages. Here, three-dimensional (3D) printing was applied to construct porous scaffolds with β-tricalcium phosphate (β-TCP) bioceramic-induced macrophage exosomes (BC-Exos). The three-dimensional-printed BC-Exo scaffolds, exhibiting a predefined structure and persistent release of exosomes, displayed distinct immunomodulatory effects and improved osteogenesis/angiogenesis. The BC-Exos in the printed scaffolds modulated macrophage polarization and the expression of chemokines for the recruitment of bone marrow mesenchymal stem cells (BMSCs) and endothelial cells. Scaffolds with BC-Exos from macrophages with a mixed phenotype significantly enhanced the osteogenic differentiation and immunosuppression of BMSCs and improved the angiogenic activity of human umbilical vein endothelial cells in vitro. For the potential mechanism, β-TCP bioceramics have an important effect on the immunomodulation of macrophages by regulating gene expression, increasing exosome production, and altering exosomal miRNA cargos, thereby affecting the paracrine effects of BC-Exos on immunomodulation and osteogenesis/angiogenesis. This study suggests that 3D printing of bioceramic-induced macrophage exosomes may be a useful strategy for tissue engineering and regenerative medicine.

Plasma Exosomes of Patients with Breast and Ovarian Tumors Contain an Inactive 20S Proteasome.

Exosomes are directly involved in governing of physiological and pathological conditions of an organism through the transfer of information from producing to receiving cells. It can be assumed that exosomes are one of the key players of tumor dissemination since they are very stable and small enough to penetrate from various tissues into biological fluids and then back, thus interacting with tissue target cells. We evaluated the enzymatic activity and the level of 20S proteasome in tissue and exosomes of healthy females (n = 39) and patients with ovarian (n = 50) and breast (n = 108) tumors to reveal the critical role of exosomal cargo in the mediation of different types of metastases. Exosomes from plasma and ascites were isolated and characterized in according to International Society for Extracellular Vesicles guidelines. The level of 20S proteasome in tissue and exosomes was determined using Western blot analysis. Chymotrypsin- and caspase-like (ChTL and CL, respectively) peptidase activities of the proteasomes were determined using fluorogenic Suc-LLVY-AMC and Cbz-LLG-AMC substrates, respectively. We observed increased levels of 20S proteasome in ovarian cancer tissue and luminal B subtype breast cancer tissue as well as in plasma exosomes from cancer patients. Moreover, the level of the 20S proteasome in plasma exosomes and ascites exosomes in patients with ovarian tumors is comparable and higher in ovarian cancer patients with low volume ascites than in patients with moderate and high-volume ascites. We also found increased ChTL and CL activities in breast cancer and ovarian cancer tissues, as well as in peritoneal metastases in ovarian cancer, while proteasomal activity in exosomes from plasma of healthy females and all patients, as well as from ascites of ovarian tumor patients were lower than detection limit of assay. Thus, regardless of the type of tumor metastasis (lymphogenous or peritoneal), the exosomes of cancer patients were characterized by an increased level of 20S proteasome, which do not exhibit enzymatic activity.

Why should the molecular characterization of inflammasome-induced exosomal cargo be done?

Why should the molecular characterization of inflammasome-induced exosomal cargo be done?

Latest Trend of Milk Derived Exosomes: Cargos, Functions, and Applications.

Exosomes are nanosized phospholipid bilayer vesicles released to the extracellular environment. Exosomes from various tissues or cells are being studied and there has been a growing interest in milk exosomes research due to their emerging role as messengers between cells and the fact that it can be produced in large quantities with rich source of milk. Milk derived exosomes (MDEs) contain lipids, microRNAs, proteins, mRNAs as well as DNA. Studies of exosome cargo have been conducted widely in many research areas, especially exosomal miRNAs. In this paper, we reviewed the current knowledge in isolation and identification, cargos, functions mainly in intestinal tract and immunity system of MDEs. Its application as drug carriers and diseases biomarker are also discussed. Furthermore, we also consider critical challenges of MDEs application and provide possible directions for future research.