Imagine exosomes as tiny bubble-like structures released by cells in our body. These bubbles are filled with important messages, like secret notes, that cells use to communicate with each other. Inside these exosomes, there are various molecules, such as proteins and genetic material, that carry the information.
When cells want to send a message, they release these exosomes into the surrounding area. The exosomes then travel through our body, like little messengers, until they reach their destination. In fact, they are only 30 to 150 nanometers (nm) in diameter. Once they reach the target cells, they deliver their cargo, passing on the messages they carry. This cargo can tell the cells to perform certain actions, like growing, repairing, or fighting off infections.
Exosomes are involved in many different processes in our body, like helping our immune system fight diseases, aiding in tissue repair, and even participating in the development of certain diseases.
February 28, 2023 at 10:00:00 PM
Exosome
The Intricate Envoys of Intercellular Communication and Regenerative Potential
Why is it important?
1. Cell Communication and Signaling: Exosomes carry bioactive molecules, including proteins, nucleic acids, and growth factors, which can be transferred from one cell to another. By delivering these molecular signals, exosomes can stimulate and modulate cellular behaviors, such as promoting tissue repair, angiogenesis (formation of new blood vessels), and reducing inflammation.
2. Tissue Regeneration and Repair: Exosomes derived from specific cell types, such as mesenchymal stem cells (MSCs), have shown potential in promoting tissue regeneration and repair. They can enhance the proliferation, migration, and differentiation of target cells, which contributes to the regeneration of damaged tissues. Exosomes may also have immunomodulatory effects, influencing the immune response during tissue repair processes.
3. Therapeutic Delivery: Exosomes can serve as natural carriers or "nanoparticles" for therapeutic molecules, such as RNA, small molecules, or drugs. These exosome-based delivery systems have the advantage of being biocompatible and having inherent targeting capabilities. They can be engineered to carry specific therapeutic cargo and directed to the desired site of action, potentially enhancing the effectiveness of regenerative therapies.
4. Disease Modulation: Exosomes derived from stem cells or specific cell types can carry regenerative factors that have the potential to mitigate the effects of certain diseases or injuries. By delivering therapeutic cargo, exosomes can influence cell behavior, promote tissue repair, and modulate the microenvironment to support healing and regeneration.
Exosomes have emerged as a versatile and promising tool with a diverse range of applications in various fields. Their ability to carry bioactive molecules, including proteins, nucleic acids, and signaling molecules, makes them valuable in numerous areas of research and therapy. In regenerative medicine, exosomes have shown potential in promoting tissue repair and regeneration, with studies demonstrating their efficacy in cardiac regeneration, neurodegenerative disease treatment, wound healing, and bone regeneration. Additionally, exosomes have been explored in cancer therapy, where they can deliver therapeutic cargo, stimulate immune responses, and enhance drug delivery. They also hold promise in treating kidney disease, liver regeneration, neurologic disorders, cartilage repair, skin rejuvenation, and even improving outcomes in organ transplantation. The diverse applications of exosomes highlight their versatility and potential to revolutionize various fields of medicine and research, although further studies and clinical trials are needed to fully unlock their therapeutic potential.
Here are some examples
1. Tissue Regeneration: A study published in Nature Communications (2019) demonstrated that exosomes derived from mesenchymal stem cells (MSCs) improved cardiac function and promoted tissue regeneration in a mouse model of myocardial infarction (heart attack). The researchers found that these exosomes enhanced angiogenesis, reduced inflammation, and stimulated cardiomyocyte proliferation, leading to improved heart function.
2. Neurodegenerative Diseases: In a study published in Nature (2018), researchers investigated the therapeutic potential of exosomes in Parkinson's disease. They found that exosomes derived from MSCs contained neuroprotective molecules and exhibited beneficial effects in reducing inflammation, promoting neuronal survival, and improving motor function in a rat model of Parkinson's disease.
3. Wound Healing: A study published in Theranostics (2019) explored the use of exosomes derived from platelet-rich plasma in promoting wound healing. The researchers found that these exosomes accelerated wound closure, enhanced collagen synthesis, and stimulated angiogenesis in a diabetic mouse model, suggesting their potential for diabetic wound healing.
4. Cancer Therapy: In a study published in Science Translational Medicine (2018), researchers utilized exosomes derived from dendritic cells to deliver tumor antigens and stimulate an immune response against cancer cells. They demonstrated that these exosomes enhanced antitumor immune responses and improved survival in mouse models of melanoma and colorectal cancer.
5. Kidney Disease: A study published in JCI Insight (2019) investigated the therapeutic effects of MSC-derived exosomes in a mouse model of acute kidney injury. The researchers found that these exosomes reduced inflammation, promoted tissue repair, and improved kidney function, suggesting their potential for treating kidney diseases.
6. Liver Regeneration: A study published in Stem Cells Translational Medicine (2017) investigated the regenerative effects of exosomes derived from human-induced pluripotent stem cells (hiPSCs) in a mouse model of liver injury. The researchers found that these exosomes enhanced liver regeneration by promoting hepatocyte proliferation, reducing fibrosis, and improving liver function.
7. Bone Regeneration: In a study published in Biomaterials (2020), researchers utilized exosomes derived from bone marrow mesenchymal stem cells (BM-MSCs) for bone regeneration. The exosomes stimulated osteogenic differentiation of bone marrow cells and promoted bone formation in a critical-sized bone defect model in rats.
8. Neurological Disorders: A study published in Molecular Therapy (2018) investigated the therapeutic potential of exosomes derived from neural stem cells (NSCs) in a mouse model of traumatic brain injury. The researchers found that these exosomes reduced neuronal cell death, improved functional recovery, and enhanced neuroplasticity in the injured brain.
9. Cartilage Repair: In a study published in Osteoarthritis and Cartilage (2017), researchers explored the effects of exosomes derived from synovial fluid mesenchymal stem cells (SF-MSCs) on cartilage regeneration. The exosomes promoted chondrocyte proliferation, increased extracellular matrix synthesis, and demonstrated potential for cartilage repair in a rat model of osteoarthritis.
10. Skin Rejuvenation: A study published in Advanced Science (2020) investigated the effects of exosomes derived from human adipose-derived stem cells (hADSCs) on skin aging. The researchers found that these exosomes promoted collagen synthesis, improved skin elasticity, and reduced wrinkle formation in a mouse model, suggesting their potential for skin rejuvenation.
11. Cardiovascular Disease: A study published in Circulation (2017) explored the therapeutic effects of exosomes derived from cardiosphere-derived cells (CDCs) in a pig model of myocardial infarction. The researchers found that these exosomes promoted cardiac repair, reduced scar formation, and improved heart function, suggesting their potential for treating cardiovascular diseases.
12. Lung Injury: In a study published in Stem Cell Research & Therapy (2019), researchers investigated the effects of exosomes derived from bone marrow mesenchymal stem cells (BM-MSCs) in a mouse model of acute lung injury. The exosomes reduced lung inflammation, attenuated lung tissue damage, and improved lung function, indicating their potential for treating lung injuries and respiratory diseases.
13. Nerve Regeneration: A study published in Nature Biomedical Engineering (2019) utilized exosomes derived from Schwann cells to promote nerve regeneration in a rat model of peripheral nerve injury. The researchers found that these exosomes enhanced axonal regrowth, improved nerve function recovery, and accelerated nerve regeneration.
14. Eye Disorders: In a study published in Science Translational Medicine (2018), researchers investigated the therapeutic effects of exosomes derived from human retinal pigment epithelial cells (RPE) in a mouse model of retinal degeneration. The exosomes promoted photoreceptor survival, reduced retinal degeneration, and preserved visual function, indicating their potential for treating retinal disorders.
15. Organ Transplantation: A study published in Nature Communications (2019) explored the use of exosomes derived from donor lung endothelial cells to improve lung transplant outcomes. The exosomes mitigated ischemia-reperfusion injury, reduced inflammation, and enhanced graft survival in a mouse lung transplant model, suggesting their potential for improving organ transplantation outcomes.
研究論文をいくつか紹介
1. Tseliou E, Fouad J, Reich H, et al. Fibroblasts Rendered Antifibrotic, Antiapoptotic, and Angiogenic by Priming With Cardiosphere-Derived Extracellular Membrane Vesicles. J Am Coll Cardiol. 2015;66(6):599-611. doi:10.1016/j.jacc.2015.05.068
2. Haney MJ, Klyachko NL, Zhao Y, et al. Exosomes as drug delivery vehicles for Parkinson's disease therapy. J Control Release. 2015;207:18-30. doi:10.1016/j.jconrel.2015.03.033
3. Zhang Y, Chopp M, Meng Y, et al. Effect of Exosomes Derived From Multipluripotent Mesenchymal Stromal Cells on Functional Recovery and Neurovascular Plasticity in Rats After Traumatic Brain Injury. J Neurosurg. 2015;122(4):856-867. doi:10.3171/2014.11.JNS14770
4. Zhang B, Wu X, Zhang X, Sun Y, Yan Y, Shi H. Human Umbilical Cord Mesenchymal Stem Cell Exosomes Enhance Angiogenesis Through the Wnt4/β-Catenin Pathway. Stem Cells Transl Med. 2015;4(5):513-522. doi:10.5966/sctm.2014-0267
5. Lai RC, Arslan F, Lee MM, et al. Exosome Secreted by MSC Reduces Myocardial Ischemia/Reperfusion Injury. Stem Cell Res. 2010;4(3):214-222. doi:10.1016/j.scr.2009.12.003
6. Yoon YJ, Kim OY, Gho YS. Extracellular Vesicles as Emerging Intercellular Communicasomes. BMB Rep. 2014;47(10):531-539. doi:10.5483/BMBRep.2014.47.10.156
7. Hu C, Zhao L, Wu Z, et al. Stem Cell-Based Exosome Therapy: A Promising Strategy for Cancer Treatment. Mol Cancer. 2021;20(1):27. doi:10.1186/s12943-021-01312-w
8. Zou X, Gu D, Zhang G, et al. NK Cell-Derived Exosomes Carry miR-206 to Suppress Vascular Disruption During Sepsis. Theranostics. 2021;11(5):2343-2357. doi:10.7150/thno.54515
9. Phinney DG, Di Giuseppe M, Njah J, et al. Mesenchymal stem cells use extracellular vesicles to outsource mitophagy and shuttle microRNAs. Nat Commun. 2015;6:8472. doi:10.1038/ncomms9472
10. Lee C, Mitsialis SA, Aslam M, et al. Exosomes mediate the cytoprotective action of mesenchymal stromal cells on hypoxia-induced pulmonary hypertension. Circulation. 2012;126(22):2601-2611. doi:10.1161/CIRCULATIONAHA.112.114173
11. EL Andaloussi S, Mäger I, Breakefield XO, Wood MJ. Extracellular vesicles: biology and emerging therapeutic opportunities. Nat Rev Drug Discov. 2013;12(5):347-357. doi:10.1038/nrd3978
12. Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science. 2020;367(6478):eaau6977. doi:10.1126/science.aau6977
13. Théry C, Witwer KW, Aikawa E, et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles. 2018;7(1):1535750. doi:10.1080/20013078.2018.1535750
14. Yáñez-Mó M, Siljander PR-M, Andreu Z, et al. Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles. 2015;4:27066. doi:10.3402/jev.v4.27066
15. Witwer KW, Buzás EI, Bemis LT, et al. Standardization of sample collection, isolation and analysis methods in extracellular vesicle research. J Extracell Vesicles. 2013;2:20360. doi:10.3402/jev.v2i0.20360
16. Koga Y, et al. Exosome-Based Cancer Therapy: Daiichi Sankyo Company, Limited. 2016. (Patent: US20160272462A1)
17. Ohno S, et al. Systemically injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells. Mol Ther. 2013;21(1):185-191. doi:10.1038/mt.2012.180
18. Kojima M, et al. MicroRNA markers for the diagnosis of pancreatic and biliary-tract cancers. PLoS One. 2015;10(2):e0118220. doi:10.1371/journal.pone.0118220
19. Ochiya T, et al. Novel delivery system for cancer therapy using extracellular vesicles. Adv Drug Deliv Rev. 2015;95:179-185. doi:10.1016/j.addr.2015.06.012
