We have collected the most exciting new researches in the field of genetics and cellular research in the past week.
Clinical Applications of Exosomes: A Critical Review
Exosomes, small membrane-bound vesicles secreted by cells, have gained significant attention for their therapeutic potential. Measuring 30-100 nm in diameter and derived from various cell types, exosomes play a crucial role in intercellular communication by transferring proteins, lipids, and RNA between cells. This review analyzes existing literature on the clinical applications of exosomes. We conducted a comprehensive search of peer-reviewed articles and clinical trial data to evaluate the benefits, limitations, and challenges of exosome-based therapies. Key areas of focus included regenerative medicine, cancer therapy, gene therapy, and diagnostic biomarkers. This review highlights the vast clinical applications of exosomes. In regenerative medicine, exosomes facilitate tissue repair and regeneration. In cancer therapy, exosomes can deliver therapeutic agents directly to tumor cells. In gene therapy, exosomes serve as vectors for gene delivery. As diagnostic biomarkers, they are useful in diagnosing various diseases. Challenges such as the isolation, purification, and characterization of exosomes were identified. Current clinical trials demonstrate the potential of exosome-based therapies, though they also reveal significant hurdles. Regulatory issues, including the need for standardization and validation of exosome products, are critical for advancing these therapies. While significant progress has been made in understanding exosome biology, further research is essential to fully unlock their clinical potential. Addressing challenges in isolation, purification, and regulatory standardization is crucial for their successful application in clinical practice. This review provides a concise overview of the clinical applications of exosomes, emphasizing both their therapeutic promise and the obstacles that need to be overcome.
Novel exosome-based drug delivery system for synergistic cancer treatment
Ovarian cancer is one of the most common malignancies in women worldwide. Unlike breast cancer, ovarian cancer lacks early diagnostic markers and does not show noticeable symptoms until cancer metastases, leading to a low survival rate for ovarian cancer patients. Traditional cancer treatments include surgery, radiation therapy, chemotherapy and interventional therapy. However, the distribution of chemotherapeutic drugs in vivo is non-specific and often toxic to healthy cells, leading to unsatisfactory efficacy.
In a study published in the KeAi journal Biomedical Analysis, a group of researchers from China outline a new discrimination and treatment approach -; a novel exosome-based drug delivery system that could improve the cell entry ability of drugs and the targeting of cancer cells. This approach provides a new drug delivery system and synergistic therapy idea, paving the way for future clinical applications.
Autophagy is an intracellular degradative process where a cell engulfs its own cytoplasmic proteins or organelles and encapsulates them into autophagosomes. Many studies have shown that in cancer biology, autophagy plays a dual role in tumor promotion and inhibition. Notably, inhibition of autophagy shows potential in improving the clinical treatment of cancer patients.
"We constructed a novel antitumor exosome-based drug delivery system employing the synergistic effects of miRNA-regulated autophagy inhibition and coumarin anticancer drugs to achieve effective treatment of ovarian cancer," says Xin Hua, first author of the study. "With the anti-tumor effects and intracellular visualization from 7-coumarin, the regulation of the autophagy process from encapsulated miRNA, the targeting of cancer cells from exosome, the synergistic effect and exosome-based drug delivery strategy for anti-cancer therapy showed promising prospects for in vitro and clinical applications."
Strategies for Targeting Peptide-Modified Exosomes and Their Applications in the Lungs
Exosomes belong to a subgroup of extracellular vesicles secreted by various cells and are involved in intercellular communication and material transfer. In recent years, exosomes have been used as drug delivery carriers because of their natural origin, high stability, low immunogenicity and high engineering ability. However, achieving targeted drug delivery with exosomes remains challenging. In this paper, a phage display technology was used to screen targeted peptides, and different surface modification strategies of targeted peptide exosomes were reviewed. In addition, the application of peptide-targeted exosomes in pulmonary diseases was also summarised.
Exosomes derived from BMSCs in osteogenic differentiation promote type H blood vessel angiogenesis through miR-150-5p mediated metabolic reprogramming of endothelial cells
Osteogenesis is tightly coupled with angiogenesis spatiotemporally. Previous studies have demonstrated that type H blood vessel formed by endothelial cells with high expression of CD31 and Emcn (CD31hi Emcnhi ECs) play a crucial role in bone regeneration. The mechanism of the molecular communication around CD31hi Emcnhi ECs and bone mesenchymal stem cells (BMSCs) in the osteogenic microenvironment is unclear. This study indicates that exosomes from bone mesenchymal stem cells with 7 days osteogenic differentiation (7D-BMSCs-exo) may promote CD31hi Emcnhi ECs angiogenesis, which was verified by tube formation assay, qRT-PCR, Western blot, immunofluorescence staining and µCT assays etc. in vitro and in vivo. Furthermore, by exosomal miRNA microarray and WGCNA assays, we identified downregulated miR-150-5p as the most relative hub gene coupling osteogenic differentiation and type H blood vessel angiogenesis. With bioinformatics assays, dual luciferase reporter experiments, qRT-PCR and Western blot assays, SOX2(SRY-Box Transcription Factor 2) was confirmed as a novel downstream target gene of miR-150-5p in exosomes, which might be a pivotal mechanism regulating CD31hi Emcnhi ECs formation. Additionally, JC-1 immunofluorescence staining, Western blot and seahorse assay results showed that the overexpression of SOX2 could shift metabolic reprogramming from oxidative phosphorylation (OXPHOS) to glycolysis to enhance the CD31hi Emcnhi ECs formation. The PI3k/Akt signaling pathway might play a key role in this process. In summary, BMSCs in osteogenic differentiation might secrete exosomes with low miR-150-5p expression to induce type H blood vessel formation by mediating SOX2 overexpression in ECs. These findings might reveal a molecular mechanism of osteogenesis coupled with type H blood vessel angiogenesis in the osteogenic microenvironment and provide a new therapeutic target or cell-free remedy for osteogenesis impaired diseases.
A study of antigen selection by extracellular vesicles as vaccine candidates against Mycobacterium tuberculosis infection
Introduction. Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis (M. tb), remains a significant global public health concern. It is crucial to develop more effective vaccines for TB in order to achieve global control of the disease. Extracellular vesicles (EVs) are spherical membrane-bound structures released by pathogens and host cells. During the course of an infection, both pathogen- and host-derived EVs are produced and play important roles in determining the course of the infection. EVs offer intriguing tools as potential vaccines due to their ability to deliver multiple pathogen or host antigens.
Hypothesis /Gap Statement. We hypothesized that EVs derived from M. tb and EVs from M. tb-infected macrophages may serve as potential vaccine candidates against M. tb infection.
Aim. This study aims to compare the immunogenicity and immune protection between M. tb EVs and M. tb-infected macrophage-derived EVs.
Methodology. In this study, EVs were extracted from culture supernatants of M. tb and M. tb-infected macrophages, respectively. Mass spectrometry was employed to explore the antigen composition of H37Rv-Mφ-EVs and H37Rv-EVs. Cytokine profiling and antibody response assays were used to analyse the immunogenicity offered by EVs. Additionally, we used histological examination to evaluate and protective efficacy of the EVs.
Results. Our results demonstrated that mice immunized by EVs released from M. tb-infected macrophages induced stronger inflammatory cytokine response than M. tb. Moreover, EVs from M. tb-infected macrophages reinforced T-cell activation and antibody response compared to M. tb EVs. Proteomic analysis revealed that EVs from M. tb-infected macrophages containing immunodominant cargos have stronger binding ability with major histocompatibility complex molecules, which may contribute to the protection from M. tb infection. Indeed, immunization of EVs released from M. tb-infected macrophages significantly reduced the bacterial load and better protection against M. tb infection than EVs from M. tb. Importantly, the selected antigens (Ag85B, ESAT-6 and the Rv0580c) from EVs of M. tb-infected macrophages exhibited effective immunogenicity.
Conclusion. Our results suggested that EVs derived from M. tb-infected macrophages might serve as a proper antigenic library for vaccine candidates against M. tb challenge.
Harnessing exosomes as cancer biomarkers in clinical oncology
Exosomes are extracellular vesicles well known for facilitating cell-to-cell communication by distributing essential macromolecules like proteins, DNA, mRNA, lipids, and miRNA. These vesicles are abundant in fluids distributed throughout the body, including urine, blood, saliva, and even bile. They are important diagnostic tools for breast, lung, gastrointestinal cancers, etc. However, their application as cancer biomarkers has not yet been implemented in most parts of the world. In this review, we discuss how OMICs profiling of exosomes can be practiced by substituting traditional imaging or biopsy methods for cancer detection. Previous methods like extensive imaging and biopsy used for screening were expensive, mostly invasive, and could not easily provide early detection for various types of cancer. Exosomal biomarkers can be utilized for routine screening by simply collecting body fluids from the individual. We anticipate that the use of exosomes will be brought to light by the success of clinical trials investigating their potential to enhance cancer detection and treatment in the upcoming years.