Significance Of Exosomes Research Articles

Hierarchical microstructure design of multifunctional soft collagen-incorporated 3D hard polyetherketoneketone scaffolds for augmented bone regeneration

Implant-associated infections and insufficient osseointegration are still great challenges in clinical load-bearing applications. Exploiting the antibacterial effects and immunomodulatory properties of biomaterials has garnered substantial attention. Inspired by structural and functional cues in bone regeneration, a universal approach was proposed in which a hydroxyapatite (HAp) coating was built on 3D printed polyetherketoneketone (PEKK) scaffold, and a bioactive component-loaded soft mineralized collagen hydrogel was incorporated into 3D hard PEKK scaffold. While the PEKK scaffold exhibited exceptional mechanical performance, in vitro and in vivo data confirmed that exosomes derived from rat bone marrow mesenchyme stem cells (rBMSCs) loaded on collagen hydrogel facilitate efficient osteoimmunomodulation of the PEKK-based scaffold (denoted as the PEKK-HAp-Col/Exo scaffold). Additionally, vancomycin-loaded nanoparticles cross-linked with collagen hydrogel endowed the PEKK-based scaffold (denoted as the PEKK-HAp-Col/Van scaffold) with enhanced antibacterial effects. Overall, this study not only sheds light on the significance of exosomes in the osteoimmunomodulation of an implant but also presents a universal material–structure–function integrated strategy to fabricate multifunctional scaffolds with a soft-hard hybrid structure for clinical large-scale bone defect repair.

Calcium phosphate ceramic-induced osteoimmunomodulation: Submicron-surface-treated macrophage-derived exosomes driving osteogenesis

The development of osteoimmunology has highlighted the crucial role of biomaterial surface topography in modulating macrophage responses, subsequently affecting bone formation. However, the underlying mechanism remains largely unexplored. This study introduced two biphasic calcium phosphate (BCP) ceramics with different surface architecture, finding that compared to micron-scale counterparts (BCP2, ∼3.07 μm), BCP with submicron-scale structure (BCP1, ∼0.66 μm) enhanced ectopic bone formation and facilitated M2 macrophage polarization in vivo. Previous studies have focused predominantly on soluble cytokines secreted by macrophages, the significance of exosomes in intercellular communication has been overlooked. This study isolated exosomes from macrophages treated with either submicron- or micron-scale surfaces, designated as B1-Exos and B2-Exos, respectively. Notably, B1-Exos could significantly improve osteogenic differentiation of mesenchymal stem cells (MSCs), potentially attributable to miRNA cargos within these exosomes. SmallRNA sequencing, western blotting, qRT-PCR, and bioinformatics analyses indicated that submicron-sized BCP1 ceramic markedly elevated miR-142a-5p levels in macrophage-derived exosomes, activating the PTEN/AKT signaling pathway, and consequently guiding the differentiation of MSCs towards osteoblast lineage. These findings not only deepen our understanding of the biomaterial-mediated osteoinduction mechanism, but also inform the design of bone repair materials with specialized surface design for proper immunomodulation to initiate osteogenesis.

Irradiated Cell-derived Exosomes Enhance Cell Proliferation and Radioresistance via the MAPK/Erk Pathway.

Radiation therapy is pivotal in cancer treatment; however, its efficacy is limited by challenges such as tumor recurrence. This study delves into the role of exosomes, which are molecular cargo-bearing vesicles, in influencing cell proliferation, radioresistance, and consequent post-irradiation tumor recurrence. Given the significance of exosomes from irradiated malignancies in diagnostics and therapy, it is vital to delineate their functional dynamics, especially in breast and cervical cancer cell lines, where the impact of irradiation on exosome behavior remains enigmatic. Using MDA-MB-231 and HeLa cell lines, exosomes were isolated from the culture supernatant via ultracentrifugation. The bicinchoninic acid assay was used to measure exosome quantities in irradiated and non-irradiated cells. Radiosensitivity was assessed using colony formation assays, while the role of the MAPK/Erk signaling pathway in recipient cell proliferation and radioresistance was probed using western blotting. Irradiated cells, in both MDA-MB-231 and HeLa lines, produced significantly more exosomes than their non-irradiated counterparts. Co-culturing irradiated cells with exosomes led to increased cell survival post-irradiation and enhanced cell proliferation in both cell lines. Western blotting indicated elevated p-Erk expression in such cells, underscoring the influence of the MAPK/Erk pathway in radioresistance and proliferation. The study establishes a potential nexus between exosome secretion and tumor resurgence following radiotherapy. The spotlight falls on the MAPK/ERK signaling conduit as a key influencer. This new knowledge provides an innovative strategy for counteracting cancer recurrence after radiotherapy, emphasizing the importance of understanding the multifaceted roles of exosomes in this context.

Exosomal lncRNA Mir100hg derived from cancer stem cells enhance glycolysis and promote metastasis of lung adenocarcinoma through mircroRNA-15a-5p/31-5p

BackgroundExosomes are a new class of molecular entities in the metastatic microenvironment, which can mediate bidirectional communication between cells. While exosomes-mediated interactions between tumor cells and other cell populations in the tumor microenvironment have attracted most attention, little is known about the significance of exosomes in mediating the interaction between non-stemness cancer cells and cancer stem cells during cancer progression.MethodsThe structure, sequence and downstream target miRNAs of lncRNA Mir100hg were predicted by online web resources. The bioinformatics prediction results were validated with experimental verification: exosome tracing, electron microscopy, Luciferase assay, metabolomics sequencing and mouse tail vein model of pulmonary metastasis. A complex regulatory network of "cancer stem cells-exosomal lncRNA-non-stem cancer cells" was constructed.ResultsThis study demonstrates firstly that lncRNA Mir100hg is upregulated in lung cancer stem cell LLC-SD (Lung cancer stem cells) and can be delivered to non-stemness cancer cells LLC (Lewis lung cancer cells) via exosomes. In LLC, Mir100hg targets miR-15a-5p and miR-31-5p which leads to the increase of the global glycolytic activity of lung cancer cells and consequently, the enhancement of their metastatic capability.ConclusionWe delineated a complex regulatory network that utilized by cancer stem cells to transfer their high metastatic activity to the low-metastatic non-stemness cancer cells through exosomal Mir100hg, thereby providing new mechanistic insights into the communication between two heterogeneous tumor cells.EX9vzfLURWcPee8x9snm8iVideo

Regulatory role of exosomes in colorectal cancer progression and potential as biomarkers.

Colorectal cancer (CRC) remains an enormous challenge to human health worldwide. Unfortunately, the mechanism underlying CRC progression is not well understood. Mounting evidence has confirmed that exosomes play a vital role in CRC progression, which has attracted extensive attention among researchers. In addition to acting as messengers between CRC cells, exosomes also participate in the CRC immunomodulatory process and reshape immune function. As stable message carriers and liquid biopsy option under development, exosomes are promising biomarkers in the diagnosis or treatment of CRC. In this review we have described and analyzed the biogenesis and release of exosomes and current research on the role of exosomes in immune regulation and metastasis of CRC. Moreover, we have discussed candidate exosomal molecules as potential biomarkers to diagnose CRC, predict CRC progression, or determine CRC chemoresistance, and described the significance of exosomes in the immunotherapy of CRC. This review provides insight to further understand the role of exosomes in CRC progression and identify valuable biomarkers that facilitate the clinical management of CRC patients.

Significance of exosomes in hepatocellular carcinoma.

Among the most prevalent cancers in the world, hepatocellular carcinoma (HCC) has a high mortality rate. The diagnosis and management of HCC are presently hindered by difficulties in early detection and suboptimal treatment outcomes. Exosomes have been shown to play an important role in hepatocarcinogenesis and can also be used for diagnosis and treatment. In this review, we discussed the research progress on exosomes in hepatocarcinogenesis development, tumor microenvironment remodeling, treatment resistance, and immunosuppression. HCC can be diagnosed and treated by understanding the pathogenesis and identifying early diagnostic markers. This review will be a significant reference for scholars with an initial understanding of the field to fully understand the role of exosomes in the organism.

Exosome-mediated cell–cell communication within pancreatic cancer tumor microenvironment: a narrative review

The significance of exosomes has emerged in a variety of physiological processes and diseases. Pancreatic cancer remains one of the most lethal diseases at present. Recently, increasing evidence has suggested that exosomes are vital for mediating the elaborate interaction of highly heterogeneous cell clusters within the pancreatic tumor microenvironment, contributing to activating pancreatic stellate cells and cancer-associated fibroblasts, compromising immune cells, and enhancing angiogenesis. Besides their natural and intrinsic roles, exosomes may provide a novel potential way for pancreatic cancer management and therapy as well. Thus, exosomes not only mediate cellular communication during pancreatic cancer progression but also serve as a promising player in precise pancreatic cancer management and treatment. To comprehensively summarize the role of exosomes in pancreatic cancer, we searched the PubMed database and reviewed all relevant original studies.

Regulation of in vivo fate of exosomes for therapeutic applications: New frontier in nanomedicines.

The significance of exosomes as intercellular messengers in a range of biological phenomena has hugely inspired many researchers to use them for disease diagnosis and treatment. Likewise, since the adoption of exosomes as new tools for our research, I aspired to address relevant delivery challenges with my expertise in the field of nanomedicine to develop better exosome-related therapies. In particular, innately therapeutic and exogenous drug-loaded exosomes should be located at the target site, whereas pathological exosomes or their biogenesis pathways should be targeted to control them. Reflecting recent preclinical efforts in my research group to meet such needs, the related previous work history, and initial accomplishments for regulating the in vivo fate of exosomes are covered in this contribution to the Orations-New Horizons of the Journal of Controlled Release, along with our ambitions for future developments in the field.

Abstract 6352: Ascites derived exosomes promote progression of advanced gastric cancers

Abstract Gastric cancer (GC) with peritoneal metastasis accompanied by a sequential buildup of malignant ascites currently has no curative therapy; accordingly, developing novel biomarkers is critical for reducing the severity of this disease. Recently, the significance of exosomes as a biomarker has gradually increased; exosomes act as a critical mediator of cell-cell intracellular communication in cancer progression. In this study, we characterized exosomes derived from ascites (ExoAscites) of four patients with GC; the high concentration of ExoAscites was observed with the morphology of round-cup shape. Our results showed that ExoAscites were actively endocytosed into cancer spheroid with time. The tropism of ExoAscites showed a predominance to GC rather than stromal cells.Furthermore, their importance on cancer invasiveness and angiogenesis are verified in the 3D microfluidic cancer spheroid model. Interestingly, tumor progression was gradually promoted by treatment with increasing ExoAscites concentrations. Collectively, these results support the view that exosomes from ascites fluids act as mediators of the tumor microenvironment, thus providing conditions favorable for future tumor progression. Citation Format: Sujin Hyung, Jihoon Ko, In-kyung Lee, Noo Li Jeon, Jeeyun Lee. Ascites derived exosomes promote progression of advanced gastric cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6352.

Significance of exosomes in cardiology: heralds of cardioprotection

ResumenLos exosomas tienen un papel clave en la comunicación intercelular. Debido a sus múltiples interacciones, estas estructuras cumplen con el papel de «mensajeros» de forma dinámica, transportando su contenido a células blanco específicas y generando nuevas señales celulares. En este artículo se describen algunas de las proteínas, lípidos y ácidos nucleicos que son transportados por estas vesículas y que se han relacionado con cardioprotección, con la finalidad de proporcionar información y generar interés sobre la relevancia de los exosomas como posibles blancos diagnósticos y terapéuticos.

Significance of exosomes in Cardiology: Heralds of cardioprotection

Significance of exosomes in Cardiology: Heralds of cardioprotection

Exosomes in osteoarthritis and cartilage injury: advanced development and potential therapeutic strategies.

Articular cartilage injury is a common clinical problem, which can lead to joint dysfunction, significant pain, and secondary osteoarthritis (OA) in which major surgical procedures are mandatory for treatment. Exosomes, as endosome-derived membrane-bound vesicles, participating in intercellular communications in both physiological and pathophysiological conditions, have been attached great importance in many fields. Recently, the significance of exosomes in the development of OA has been gradually concerned, while the therapeutic value of exosomes in cartilage repair and OA treatment has also been gradually revealed. The functional difference of different types and derivations of exosomes are determined by their specific contents. Herein, we provide comprehensive understanding on exosome and OA, including how exosomes participating in OA, the therapeutic value of exosomes for cartilage injury/OA, and related bioengineering strategies for future therapeutic design.

Elevated Levels of Serum Exosomes in Patients with Major Depressive Disorder

Exosomes are small (30–100 nm) vesicles of the endocytic membrane that may be found in the endosome system of multivesicular organs and are released after fusion of multivesicular bodies with the plasma membrane. Exosomes function as carriers for specific loads and are stable in biological fluids; hence, exosomes are considered as potential biomarkers of different diseases. The degree of involvement and functional significance of exosomes in pathogenesis of depression have been poorly studied. The development of diagnostic methods for depressive disorders based on the analysis of circulating exosomes is very promising, despite the methodological complications related to their isolation and identification. The purpose of this study was to isolate exosomes from the blood serum of patients with major depressive disorder (MDD) and compare them with healthy volunteers using different methods of evaluation. The concentration of serum exosomes assessed using the methods of dynamic light scattering, nanoparticle tracking analysis, and the enzyme-linked immunoassay was statistically elevated in patients with MDD compared to healthy volunteers. The possible connection between the increased level of serum exosomes with the cell-mediated immune activation that is seen in depression is discussed.

Emergence of exosomal DNA in molecular neuropathology

AbstractBackground:Exosomes are small vesicles of sizes between 40 and 100 nm. They are actively segregated by numerous different cell types and they can be found in almost all body fluids. Thus, there is an emerging role of exosomes and exosomal deoxyribonucleic acid (exoDNA) in biomedical research, especially in molecular medicine. Exosomes are assembled and segregated actively and carry distinct surface markers for cellular communication. They are loaded with cargo such as DNA, ribonucleic acid (RNA) and proteins. As there are numerous different exosomal purification methods available, it is of essential need to select an appropriate technique to get reliable results. As neuropathology is faced with the challenge that brain tissue is not accessible in an easy fashion, exosomes represent an ideal tool for molecular neuropathology. Thus, disease-specific molecular alterations will be detectable in a minimally invasive way for early disease diagnosis and surveillance.Summary:The analysis of exoDNA as biomarkers in neuropathology will enable early diagnosis, monitoring and relapse detection of brain tumors and neuropsychiatric disorders.Outlook:It is assumed that the significance of exosomes will increase in the upcoming years. There are powerful approaches in development using exosomes in molecularly targeted therapy to ultimately cure devastating brain diseases.