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Weekly Exosomes Digest (1/4 November 2023)

We have collected the most exciting new researches in the field of genetics and cellular research in the past week.



Research Advances of Engineered Exosomes as Drug Delivery Carrier


Abstract Exosomes are nanoscale vesicles secreted by living cells that have similar membrane composition to parental cells and carry a variety of proteins, lipids, and nucleic acids. Therefore, exosomes have certain biological activities and play an important role in intercellular communication. On the basis of its potential as a carrier for drug delivery systems, exosomes have been engineered to compensate for the shortage of natural exosomes through various engineering strategies for improving drug delivery efficiency, enhancing targeting to tissues and organs, and extending the circulating half-life of exosomes. This review focuses on the engineered exosomes loading drugs through different strategies, discussions on exosome surface modification strategies, and summarizes the advantages and disadvantages of different strategies. In addition, this review provides an overview of the recent applications of engineered exosomes in a number of refractory and relapsable diseases. This review has the potential to provide a reference for further research and development of engineered exosomes.



Spatial exosome analysis using cellulose nanofiber sheets reveals the location heterogeneity of extracellular vesicles


Abstract Extracellular vesicles (EVs), including exosomes, are recognized as promising functional targets involved in disease mechanisms. However, the intravital heterogeneity of EVs remains unclear, and the general limitation for analyzing EVs is the need for a certain volume of biofluids. Here, we present cellulose nanofiber (CNF) sheets to resolve these issues. We show that CNF sheets capture and preserve EVs from ~10 μL of biofluid and enable the analysis of bioactive molecules inside EVs. By attaching CNF sheets to moistened organs, we collect EVs in trace amounts of ascites, which is sufficient to perform small RNA sequence analyses. In an ovarian cancer mouse model, we demonstrate that CNF sheets enable the detection of cancer-associated miRNAs from the very early phase when mice did not have apparent ascites, and that EVs from different locations have unique miRNA profiles. By performing CNF sheet analyses in patients, we identify further location-based differences in EV miRNA profiles, with profiles reflecting disease conditions. We conduct spatial exosome analyses using CNF sheets to reveal that ascites EVs from cancer patients exhibit location-dependent heterogeneity. This technique could provide insights into EV biology and suggests a clinical strategy contributing to cancer diagnosis, staging evaluation, and therapy planning.



UC engineering researcher studying exosomes for potential nerve regeneration awarded $2M NIH grant


Leyla Esfandiari, an associate professor of biomedical engineering at the University of Cincinnati, has received $2 million from the National Institute of General Medical Sciences to fund her research on small extracellular vesicles called exosomes and the role they play in nerve regeneration as treatment for nerve injuries or other neurodegenerative diseases.



Exosome Therapy: A New Frontier in Healthcare


In the ever-evolving field of healthcare, advancements and innovations are continually reshaping the landscape of medical treatments. One such groundbreaking development that has been gaining significant attention is exosome therapy. These tiny, extracellular vesicles have emerged as a promising avenue for treating various medical conditions. In this blog post, you will delve into the world of exosome therapy, exploring what exosomes are, their potential applications in healthcare, and the exciting prospects they offer for the future of medicine.




Application of exosomes as nanocarriers in cancer therapy


Abstract

Cancer remains the most common lethal disease in the world. Although the treatment choices for cancer are still limited, significant progress has been made over the past few years. By improving targeted drug therapy, drug delivery systems promoted the therapeutic effects of anti-cancer medications. Exosome is a kind of natural nanoscale delivery system with natural substance transport properties, good biocompatibility, and high tumor targeting, which shows great potential in drug carriers, thereby providing novel strategies for cancer therapy. In this review, we present the formation, distribution, and characteristics of exosomes. Besides, extraction and isolation techniques are discussed. We focus on the recent progress and application of exosomes in cancer therapy in four aspects: exosome-mediated gene therapy, chemotherapy, photothermal therapy, and combination therapy. The current challenges and future developments of exosome-mediated cancer therapy are also discussed. Finally, the latest advances in the application of exosomes as drug delivery carriers in cancer therapy are summarized, which provide practical value and guidance for the development of cancer therapy.




Mesenchymal stem cell-derived exosomes for managing graft-versus-host disease: An updated view


Abstract

Graft-versus-host disease (GvHD) is the most common complication after stem cell transplantation, and also it is one of the primary limiting factors for the use of hematopoietic stem cell transplantation (HSCT) in the treatment of hematologic cancers. GvHD, a systemic inflammatory disease, is caused by donor T cells recognizing the recipient's foreign antigens. In addition, an immune dysregulation, caused by autoreactive immune cells, complicates potent inflammatory process following HSCT. While there is no one approved treatment method for GvHD, corticosteroids are the most common first-line treatment. Exosomes are biological vesicles between 30 and 120 nm in diameter, which carry various biologically active molecules. They are known to play a key role in the paracrine effect of mesenchymal stem cells with therapeutic and tissue repair effects, including an immunosuppressive potential. Exosomes are unable to replicate themselves but because of their small size and fluid-like structure, they can pass through physiological barriers. Exosome are relatively easy to prepare and they can be quickly sterilized by a filtration process. Administration of exosomes, derived from mesenchymal stem cells, effectively reduced GvHD symptoms and significantly increased HSCT recipients' survival. Mesenchymal stem cell-derived exosome therapy reduced clinical symptoms of GvHD in patients after HSCT. Studies in patients with GvHD described that that mesenchymal stem cell-derived exosomes inhibited the release of IFN-γ and TNF-α by activated natural killer (NK cells), thereby reducing the lethal function of NK cells and inflammatory responses. Current review provides a comprehensive overview about the use of mesenchymal stem cells and their derived exosomes for the treatment of GvHD.


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