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Exosomes: Messenger of Cellular Communication and Regeneration

Amidst the fascinating realm of cellular biology, a microscopic marvel known as exosomes emerges as a groundbreaking entity, holding immense promise for therapeutic breakthroughs. Exosomes are a subtype of extracellular vesicles that are small membrane-bound vesicles derived from endosomes. They range in size from 30 to 150 nm and are secreted by almost all eukaryotic cells. These vesicles can be found in various bodily fluids such as plasma, urine, milk, saliva, and cerebral spinal fluid. These remarkable nanosized messengers carry a diverse range of bioactive molecules, such as proteins, lipids, and nucleic acids, allowing them to form a complex cargo that facilitates cell-to-cell communication [1]. The composition of exosomal cargos can vary significantly depending on the cell type and state, including stress, stimulation, differentiation, and transformation. Due to their biologically active cargos, exosomes have the potential to provide prognostic information for various diseases, including chronic inflammation, cardiovascular diseases, and tumors. This characteristic positions exosomes as promising candidates for non-invasive diagnostic methods [2].

Similarly, mesenchymal stem cell-derived exosomes (MSC-EVs) have garnered significant interest for their therapeutic potential in treating degenerative diseases like osteoarthritis [3] and Alzheimer's disease [4]. Research has demonstrated that MSC-EVs possess tissue regeneration capabilities, promote angiogenesis, and exhibit favorable immune regulatory properties [5]. Consequently, they are being extensively investigated as an alternative to traditional cell-based therapies, as exosome-based treatments can circumvent concerns related to necrosis or abnormal differentiation and mitigate the risk of immune rejection.

Additionally, exosomes offer immense potential as natural therapeutic carriers, as they can overcome the limitations  commonly associated with synthetic drug nanocarriers. While various nanocarriers have been developed to improve pharmacokinetics and reduce side effects and toxicity, challenges such as non-specific drug targeting, immunogenicity, and toxicity persist. In contrast, exosomes, derived from biological systems, hold great promise due to their biocompatibility, ease of metabolism and excretion, and minimal toxicity and tumorigenicity. Moreover, exosomes possess the unique advantage of combining the beneficial attributes of both synthetic drug carriers and cell-mediated delivery methods. They can be engineered, loaded with active pharmaceutical ingredients, and exhibit the desired targeting capabilities [6].

Image Credits

<a href="https://www.freepik.com/free-photo/particles-virus-cells-floating_8722216.htm#query=particles-virus-cells-floating&position=1&from_view=search&track=sph">Image by kjpargeter</a> on Freepik

Citations

1. Zhang, Y., Liu, Y., Liu, H., & Tang, W. H. (2019). Exosomes: biogenesis, biologic function and clinical potential. Cell & bioscience, 9(1), 1-18.

2. Kalishwaralal K, Kwon WY, Park KS. Exosomes for Non-Invasive Cancer Monitoring. Biotechnol J. 2019 an;14(1):e1800430. doi: 10.1002/biot.201800430. Epub 2018 Nov 20. MID: 30358137.

3. Nguyen, T. H., Duong, C. M., Nguyen, X. H., & Than, U. T. T. (2021). Mesenchymal Stem Cell-Derived Extracellular Vesicles for Osteoarthritis Treatment: Extracellular Matrix Protection, Chondrocyte and Osteocyte Physiology, Pain and Inflammation Management. Cells, 10(11), 2887. https://doi.org/10.3390/cells10112887

4. Chen, Y. A., Lu, C. H., Ke, C. C., Chiu, S. J., Jeng, F. S., Chang, C. W., Yang, B. H., & Liu, R. S. (2021). Mesenchymal Stem Cell-Derived Exosomes Ameliorate Alzheimer's Disease Pathology and Improve Cognitive Deficits. Biomedicines, 9(6), 594. https://doi.org/10.3390/biomedicines9060594

5. Wei, W., Ao, Q., Wang, X., Cao, Y., Liu, Y., Zheng, S. G., & Tian, X. (2021). Mesenchymal Stem Cell-Derived Exosomes: A Promising Biological Tool in Nanomedicine. Frontiers in pharmacology, 11, 590470. https://doi.org/10.3389/fphar.2020.590470

2. Wan, R., Hussain, A., Behfar, A., Moran, S. L., & Zhao, C. (2022). The therapeutic potential of exosomes in soft tissue repair and regeneration. International journal of molecular sciences, 23(7), 3869.

3. Do, A. D., Kurniawati, I., Hsieh, C. L., Wong, T. T., Lin, Y. L., & Sung, S. Y. (2021). Application of mesenchymal stem cells in targeted delivery to the brain: Potential and challenges of the extracellular vesicle-based approach for brain tumor treatment. International journal of molecular sciences, 22(20), 11187.
4. Walker, S., Busatto, S., Pham, A., Tian, M., Suh, A., Carson, K., ... & Wolfram, J. (2019). Extracellular vesicle-based drug delivery systems for cancer treatment. Theranostics, 9(26), 8001.
5. Maumus, M., Rozier, P., Boulestreau, J., Jorgensen, C., & Noël, D. (2020). Mesenchymal stem cell-derived extracellular vesicles: opportunities and challenges for clinical translation. Frontiers in Bioengineering and Biotechnology, 8, 997.

6. Tenchov, R., Sasso, J. M., Wang, X., Liaw, W. S., Chen, C. A., & Zhou, Q. A. (2022). Exosomes─Nature's Lipid Nanoparticles, a Rising Star in Drug Delivery and Diagnostics. ACS nano, 16(11), 17802–17846. https://doi.org/10.1021/acsnano.2c08774

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