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Weekly Exosomes Digest (1/4 September 2023)

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



Plant-Derived Exosome-Like Nanovesicles: Current Progress and Prospects


Abstract

Exosomes are small extracellular vesicles, ranging in size from 30– 150nm, which can be derived from various types of cells. In recent years, mammalian-derived exosomes have been extensively studied and found to play a crucial role in regulating intercellular communication, thereby influencing the development and progression of numerous diseases. Traditional Chinese medicine has employed plant-based remedies for thousands of years, and an increasing body of evidence suggests that plant-derived exosome-like nanovesicles (PELNs) share similarities with mammalian-derived exosomes in terms of their structure and function. In this review, we provide an overview of recent advances in the study of PELNs and their potential implications for human health. Specifically, we summarize the roles of PELNs in respiratory, digestive, circulatory, and other diseases. Furthermore, we have extensively investigated the potential shortcomings and challenges in current research regarding the mechanism of action, safety, administration routes, isolation and extraction methods, characterization and identification techniques, as well as drug-loading capabilities. Based on these considerations, we propose recommendations for future research directions. Overall, our review highlights the potential of PELNs as a promising area of research, with broad implications for the treatment of human diseases. We anticipate continued interest in this area and hope that our summary of recent findings will stimulate further exploration into the implications of PELNs for human health.




Bone marrow mesenchymal stem cellsderived exosomes stabilize atherosclerosis through inhibiting pyroptosis

Abstract

Objectives: This study aimed to determine the effects of bone marrow mesenchymal stem cells (BMSCs)-derived exosomes (BMSC-EXO) on atherosclerosis (AS), and its related underlying mechanisms.


Methods: Exosomes were isolated from mouse BMSCs, and identified by transmission electron microscopy (TEM), Nanosight (NTA), and western blot. A mouse AS model was established, and exosomes were injected into the tail vein. Total cholesterol (TC) and triglycerides (TG) were detected using their corresponding assay kits. The contents of IL-1β and IL-18 in serum were detected by ELISA. The mRNA and protein expression levels of GSDMD, Caspase1, and NLRP3 were detected by qRT-PCR and Western blot. Finally, aortic tissues in the Model and BMSC-EXO groups were sent for sequencing.


Results: TEM, NTA, and western blot indicated successful isolation of exosomes. Compared with the control group, the TC, TG contents, IL-1β and IL-18 concentrations of the mice in the Model group were significantly increased; nonetheless, were significantly lower after injected with BMSC-EXO than those in the Model group (p < 0.05). Compared with the control group, the expressions of NLRP3, caspase-1 and GSDMD were significantly up-regulated in the Model group (p < 0.05), while the expressions of NLRP3, caspase-1, and GSDMD were significantly down-regulated by BMSC-EXO. By sequencing, a total of 3852 DEGs were identified between the Model and BMSC-EXO group and were significantly enriched in various biological processes and pathways related to mitochondrial function, metabolism, inflammation, and immune response.


Conclusion: AS can induce pyroptosis, and BMSC-EXO can reduce inflammation and alleviate the progression of AS by inhibiting NLRP3/Caspase-1/GSDMD in the pyroptosis pathway.



Vascular wall microenvironment: exosomes secreted by adventitial fibroblasts induced vascular calcification


Abstract Background: Skin photoaging is a condition caused by long-term exposure to ultraviolet irradiation, resulting in a variety of changes in the skin, such as capillary dilation, increased or absent pigmentation, dryness, sagging, and wrinkles. Stem cells possess a remarkable antioxidant capacity and the ability to proliferate, differentiate, and migrate, and their main mode of action is through paracrine secretion, with exosomes being the primary form of secretion. Stem cell-derived exosomes contain a variety of growth factors and cytokines and may have great potential to promote skin repair and delay skin ageing.

Methods: This review focuses on the mechanisms of UV-induced skin photoaging, the research progress of stem cell exosomes against skin photoaging, emerging application approaches and limitations in the application of exosome therapy.

Result: Exosomes derived from various stem cells have the potential to prevent skin photoaging.

Conclusion: The combination with novel materials may be a key step for their practical application, which could be an important direction for future basic research and practical applications.




Differences between migrasome, a 'new organelle', and exosome


The migrasome is a new organelle discovered by Professor Yu Li in 2015. When cells migrate, the membranous organelles that appear at the end of the retraction fibres are migrasomes. With the migration of cells, the retraction fibres which connect migrasomes and cells finally break. The migrasomes detach from the cell and are released into the extracellular space or directly absorbed by the recipient cell. The cytoplasmic contents are first transported to the migrasome and then released from the cell through the migrasome. This release mechanism, which depends on cell migration, is named 'migracytosis'. The main components of the migrasome are extracellular vesicles after they leave the cell, which are easy to remind people of the current hot topic of exosomes. Exosomes are extracellular vesicles wrapped by the lipid bimolecular layer. With extensive research, exosomes have solved many disease problems. This review summarizes the differences between migrasomes and exosomes in size, composition, property and function, extraction method and regulation mechanism for generation and release. At the same time, it also prospects for the current hotspot of migrasomes, hoping to provide literature support for further research on the generation and release mechanism of migrasomes and their clinical application in the future.




Harnessing the power of exosomes for youthful skin


As the world continues to search for effective and innovative solutions to combat aging skin, a groundbreaking technology is emerging that holds immense potential in the field of dermatology. Exosomes, tiny vesicles secreted by cells, have become a focal point of extensive research due to their regenerative and immunomodulatory properties.




Coya Therapeutics Successfully Engineers Regulatory T Cell (Treg) Derived Exosomes with CTLA-4 Protein to Selectively Target Immune Cells with Potential to Deliver Targeted Therapies Across Multiple Diseases


Using proprietary exosome tethering modification technology, Treg derived exosomes were engineered with a surface protein, cytotoxic T lymphocyte associated protein 4 (CTLA-4) to increase selective targeting to immune cells; This patented technology requires no genetic modifications, overcomes known limitations of exosome manipulation, and enables tethering of multiple potential proteins to an exosome surface and loading of therapeutic cargo in the exosome interior; CTLA-4-engineered Treg exosomes (CTLA-4-Treg exosomes) dramatically increased targeting of, binding to, internalization of, and uptake into immune cells including macrophages and T cells; This technology can serve as a platform to engineer the exosome surface with proteins of interest to target specific cell and tissue types to potentially treat epitope driven autoimmune diseases and cancer.


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