Öz
Eksozomlar, hücre tarafından dışarı atılan nano ölçekte çift zar yapısına sahip yağ kesecikleri olarak bilinmektedir. İlk keşfedildiği 1980’li yıllarda, hücre atıklarının hücre dışına atılmasını gerçekleştiren kesecik yapılar olduğu düşünüldü. Günümüzde yapılan çalışmalar sonucunda, bu keseciklerin önemli fizyolojik görevleri yerine getirdiği tespit edilmiştir. Hücreler arası iletişim, sinyal iletimi, genetik materyal transferi, immünolojik yanıtın düzenlenmesi ve benzeri çok sayıda biyolojik aktivitede önemli fizyolojik rollere sahip olan bu kesecikler, hemen hemen tüm vücut sıvılarında yer almaktadır. Gerçekleştirdiği görevler nedeniyle hastalık patogenezinde de önemli bir yere sahiptir. Bu nedenle, hem tanı hem de tedavi uygulamalarında kullanımı giderek artmıştır. Farklı hücrelerden kökene sahip olan eksozomların, immün baskılayıcı ve etkinleştirici özelliklerinin varlığından dolayı otoimmün ve immün baskılama ve benzeri durumlarda immün işlevinin düzenlenmesini sağlamayı gerektiren, terapötik uygulamalarda kullanılabileceği öngörülmektedir. Bunun yanı sıra, doğal bir nanotaşıyıcı olmaları nedeniyle, eksozomlar hem adjuvanın hem de antijenin taşınabildiği yeni nesil aşıların, tasarımı ve geliştirilmesine imkân sağlamaktadır. Eksozomların tedavi edici uygulamalarının yanısıra, hastalık patogenezlerinde rol alması rolü vasıtasıyla prostat kanseri, glioblastom, akciğer yassı hücreli karsinomu ve hepatoselüler karsinom ve benzeri kanser çeşitlerinin tanısında da etkin birşekilde kullanılabileceğine dair bulgular bulunmaktadır.
Anahtar Kelimeler
Ekzozom tanı nanokesecik nanovezikül immünite kanser patogenez
Destekleyen Kurum
NA
Proje Numarası
NA
Teşekkür
Bu çalışmanın gerçekleşmesi sırasında gösterdiği değerli katkılarından dolayı, Burak Aygan lisans tez danışmanı Dr. Öğr. Üyesi Esra Cansever Mutlu’ ya teşekkür etmektedir.
Kaynakça
- 1. Vlassov, A.V., et al., Exosomes: current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochimica et Biophysica Acta (BBA)-General Subjects, 2012. 1820(7): p. 940-948.
- 2. Barile, L. and G. Vassalli, Exosomes: Therapy delivery tools and biomarkers of diseases. Pharmacology & therapeutics, 2017. 174: p. 63-78.
- 3. H Rashed, M., et al., Exosomes: from garbage bins to promising therapeutic targets. International journal of molecular sciences, 2017. 18(3): p. 538.
- 4. Valadi, H., et al., Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nature cell biology, 2007. 9(6): p. 654-659.
- 5. TAVUKÇUOĞLU, Z. and B.B. PEYNİRCİOĞLU, Enfeksiyon Hastalıklarında, Tanı ve Tedavi Yaklaşımları Açısından Eksozomlar. Turkiye Klinikleri Infectious Diseases-Special Topics, 2018. 11(2): p. 33-39.
- 6. Greening, D.W., et al. Emerging roles of exosomes during epithelial–mesenchymal transition and cancer progression. in Seminars in cell & developmental biology. 2015. Elsevier.
- 7. Darband, S.G., et al., Exosomes: natural nanoparticles as bio shuttles for RNAi delivery. Journal of Controlled Release, 2018. 289: p. 158-170.
- 8. Tatiparti, K., et al., siRNA delivery strategies: a comprehensive review of recent developments. Nanomaterials, 2017. 7(4): p. 77.
- 9. Maheshwari, R., et al., Recent advances in exosome-based nanovehicles as RNA interference therapeutic carriers. Nanomedicine, 2017. 12(21): p. 2653-2675.
- 10. Li, S.-p., et al., Exosomal cargo-loading and synthetic exosome-mimics as potential therapeutic tools. Acta Pharmacologica Sinica, 2018. 39(4): p. 542-551.
- 11. Xu, D., et al., Exosome‐encapsulated miR‐6089 regulates inflammatory response via targeting TLR4. Journal of cellular physiology, 2019. 234(2): p. 1502-1511.
- 12. TAVUKÇUOĞLU, Z., Ailevi Akdeniz Ateşi (AAA) Hastalığında Belirlenen Aday miRNA'ların Dolaşımdaki Varlığının Eksozomlar Üzerinden Araştırılması. 2018, Sağlık Bilimleri Enstitüsü.
- 13. Mutlu, E.C., et al., Exosome Production, Isolation and Characterization from A549 Epithelial Carcinoma Cells A549 Epitelyal Karsinom Hücrelerinden Eksozom Üretimi, İzolasyonu ve Karakterizasyonu. studies, 2020. 3: p. 4.
- 14. Porro, C., T. Trotta, and M.A. Panaro, Microvesicles in the brain: Biomarker, messenger or mediator? Journal of neuroimmunology, 2015. 288: p. 70-78.
- 15. Martinez, M.C., et al., Microparticles: targets and tools in cardiovascular disease. Trends in pharmacological sciences, 2011. 32(11): p. 659-665.
- 16. Andaloussi, S.E., et al., Extracellular vesicles: biology and emerging therapeutic opportunities. Nature reviews Drug discovery, 2013. 12(5): p. 347-357.
- 17. Chen, J., et al., Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats. Stroke, 2001. 32(4): p. 1005-1011.
- 18. Chen, J., et al., Neurorestorative therapy for stroke. Frontiers in human neuroscience, 2014. 8: p. 382.
- 19. Xin, H., Y. Li, and M. Chopp, Exosomes/miRNAs as mediating cell-based therapy of stroke. Frontiers in cellular neuroscience, 2014. 8: p. 377.
- 20. Théry, C., M. Ostrowski, and E. Segura, Membrane vesicles as conveyors of immune responses. Nature reviews immunology, 2009. 9(8): p. 581-593.
- 21. Xin, H., et al., Systemic administration of exosomes released from mesenchymal stromal cells promote functional recovery and neurovascular plasticity after stroke in rats. Journal of Cerebral Blood Flow & Metabolism, 2013. 33(11): p. 1711-1715.
- 22. Zhang, Z.G. and M. Chopp, Exosomes in stroke pathogenesis and therapy. The Journal of clinical investigation, 2016. 126(4): p. 1190-1197.
- 23. Luarte, A., et al., Potential therapies by stem cell-derived exosomes in CNS diseases: focusing on the neurogenic niche. Stem cells international, 2016. 2016.
- 24. Huang, M., Y.-Y. Hu, and X.-Q. Dong, High concentrations of procoagulant microparticles in the cerebrospinal fluid and peripheral blood of patients with acute basal ganglia hemorrhage are associated with poor outcome. Surgical neurology, 2009. 72(5): p. 481-489.
- 25. Chen, C.C., et al., Elucidation of exosome migration across the blood–brain barrier model in vitro. Cellular and molecular bioengineering, 2016. 9(4): p. 509-529.
- 26. Otero-Ortega, L., et al., Exosomes promote restoration after an experimental animal model of intracerebral hemorrhage. Journal of Cerebral Blood Flow & Metabolism, 2018. 38(5): p. 767-779.
- 27. Choi, D.S., et al., Proteomics of extracellular vesicles: exosomes and ectosomes. Mass spectrometry reviews, 2015. 34(4): p. 474-490.
- 28. Suzuki, E., et al., Stem cell-derived exosomes as a therapeutic tool for cardiovascular disease. World journal of stem cells, 2016. 8(9): p. 297.
- 29. Beer, L., et al., Peripheral blood mononuclear cell secretome for tissue repair. Apoptosis, 2016. 21(12): p. 1336-1353.
- 30. Qin, X., et al., Targeting Rabs as a novel therapeutic strategy for cancer therapy. Drug discovery today, 2017. 22(8): p. 1139-1147.
- 31. Essandoh, K., et al., Blockade of exosome generation with GW4869 dampens the sepsis-induced inflammation and cardiac dysfunction. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 2015. 1852(11): p. 2362-2371.
- 32. Trajkovic, K., et al., Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science, 2008. 319(5867): p. 1244-1247.
- 33. Taverna, S., et al., Curcumin modulates chronic myelogenous leukemia exosomes composition and affects angiogenic phenotype via exosomal miR-21. Oncotarget, 2016. 7(21): p. 30420.
- 34. Alvarez-Erviti, L., et al., Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nature biotechnology, 2011. 29(4): p. 341-345.
Öz
Exosomes, as a nanoparticle, are small fat vesicles, which are ejected by all cells. When they were first discovered in the 1980s, they were determined as as vesicles that allow throwing the wastes out from the cell. Currently conducted researches indicated that many steps were taken forward that these sacs have important physiological functions. These vesicles having an important role in intercellular communication, signal transmission, genetic material transfer and regulation of immunological response, and many other biological activities can be obtained from all types of body fluids. Because of their functions, it is of great interest in the pathogenesis of the diseases and therefore it is being used both in diagnosis and treatment. It has been suggested that exosomes originating from different cell roots have immune-suppressive and activating properties, therapeutic applications that will regulate immune function in auto-immune and immune suppression and similar situations. In addition, since they are natural nano-carriers, exosomes may allow the design of new generation vaccines in which both the adjuvant and the antigen which can be transported. Apart from therapeutic applications, there are findings that exosomes could be used in the diagnosis of various types of cancers such as prostate cancer, glioblastoma, lung squamous cell carcinoma and hepatocellular carcinoma because of their role in disease pathogenesis.
Anahtar Kelimeler
Exosomes, diognosis, nanovesicle, immunity, cancer, pathogenesis
Proje Numarası
NA
Kaynakça
- 1. Vlassov, A.V., et al., Exosomes: current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochimica et Biophysica Acta (BBA)-General Subjects, 2012. 1820(7): p. 940-948.
- 2. Barile, L. and G. Vassalli, Exosomes: Therapy delivery tools and biomarkers of diseases. Pharmacology & therapeutics, 2017. 174: p. 63-78.
- 3. H Rashed, M., et al., Exosomes: from garbage bins to promising therapeutic targets. International journal of molecular sciences, 2017. 18(3): p. 538.
- 4. Valadi, H., et al., Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nature cell biology, 2007. 9(6): p. 654-659.
- 5. TAVUKÇUOĞLU, Z. and B.B. PEYNİRCİOĞLU, Enfeksiyon Hastalıklarında, Tanı ve Tedavi Yaklaşımları Açısından Eksozomlar. Turkiye Klinikleri Infectious Diseases-Special Topics, 2018. 11(2): p. 33-39.
- 6. Greening, D.W., et al. Emerging roles of exosomes during epithelial–mesenchymal transition and cancer progression. in Seminars in cell & developmental biology. 2015. Elsevier.
- 7. Darband, S.G., et al., Exosomes: natural nanoparticles as bio shuttles for RNAi delivery. Journal of Controlled Release, 2018. 289: p. 158-170.
- 8. Tatiparti, K., et al., siRNA delivery strategies: a comprehensive review of recent developments. Nanomaterials, 2017. 7(4): p. 77.
- 9. Maheshwari, R., et al., Recent advances in exosome-based nanovehicles as RNA interference therapeutic carriers. Nanomedicine, 2017. 12(21): p. 2653-2675.
- 10. Li, S.-p., et al., Exosomal cargo-loading and synthetic exosome-mimics as potential therapeutic tools. Acta Pharmacologica Sinica, 2018. 39(4): p. 542-551.
- 11. Xu, D., et al., Exosome‐encapsulated miR‐6089 regulates inflammatory response via targeting TLR4. Journal of cellular physiology, 2019. 234(2): p. 1502-1511.
- 12. TAVUKÇUOĞLU, Z., Ailevi Akdeniz Ateşi (AAA) Hastalığında Belirlenen Aday miRNA'ların Dolaşımdaki Varlığının Eksozomlar Üzerinden Araştırılması. 2018, Sağlık Bilimleri Enstitüsü.
- 13. Mutlu, E.C., et al., Exosome Production, Isolation and Characterization from A549 Epithelial Carcinoma Cells A549 Epitelyal Karsinom Hücrelerinden Eksozom Üretimi, İzolasyonu ve Karakterizasyonu. studies, 2020. 3: p. 4.
- 14. Porro, C., T. Trotta, and M.A. Panaro, Microvesicles in the brain: Biomarker, messenger or mediator? Journal of neuroimmunology, 2015. 288: p. 70-78.
- 15. Martinez, M.C., et al., Microparticles: targets and tools in cardiovascular disease. Trends in pharmacological sciences, 2011. 32(11): p. 659-665.
- 16. Andaloussi, S.E., et al., Extracellular vesicles: biology and emerging therapeutic opportunities. Nature reviews Drug discovery, 2013. 12(5): p. 347-357.
- 17. Chen, J., et al., Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats. Stroke, 2001. 32(4): p. 1005-1011.
- 18. Chen, J., et al., Neurorestorative therapy for stroke. Frontiers in human neuroscience, 2014. 8: p. 382.
- 19. Xin, H., Y. Li, and M. Chopp, Exosomes/miRNAs as mediating cell-based therapy of stroke. Frontiers in cellular neuroscience, 2014. 8: p. 377.
- 20. Théry, C., M. Ostrowski, and E. Segura, Membrane vesicles as conveyors of immune responses. Nature reviews immunology, 2009. 9(8): p. 581-593.
- 21. Xin, H., et al., Systemic administration of exosomes released from mesenchymal stromal cells promote functional recovery and neurovascular plasticity after stroke in rats. Journal of Cerebral Blood Flow & Metabolism, 2013. 33(11): p. 1711-1715.
- 22. Zhang, Z.G. and M. Chopp, Exosomes in stroke pathogenesis and therapy. The Journal of clinical investigation, 2016. 126(4): p. 1190-1197.
- 23. Luarte, A., et al., Potential therapies by stem cell-derived exosomes in CNS diseases: focusing on the neurogenic niche. Stem cells international, 2016. 2016.
- 24. Huang, M., Y.-Y. Hu, and X.-Q. Dong, High concentrations of procoagulant microparticles in the cerebrospinal fluid and peripheral blood of patients with acute basal ganglia hemorrhage are associated with poor outcome. Surgical neurology, 2009. 72(5): p. 481-489.
- 25. Chen, C.C., et al., Elucidation of exosome migration across the blood–brain barrier model in vitro. Cellular and molecular bioengineering, 2016. 9(4): p. 509-529.
- 26. Otero-Ortega, L., et al., Exosomes promote restoration after an experimental animal model of intracerebral hemorrhage. Journal of Cerebral Blood Flow & Metabolism, 2018. 38(5): p. 767-779.
- 27. Choi, D.S., et al., Proteomics of extracellular vesicles: exosomes and ectosomes. Mass spectrometry reviews, 2015. 34(4): p. 474-490.
- 28. Suzuki, E., et al., Stem cell-derived exosomes as a therapeutic tool for cardiovascular disease. World journal of stem cells, 2016. 8(9): p. 297.
- 29. Beer, L., et al., Peripheral blood mononuclear cell secretome for tissue repair. Apoptosis, 2016. 21(12): p. 1336-1353.
- 30. Qin, X., et al., Targeting Rabs as a novel therapeutic strategy for cancer therapy. Drug discovery today, 2017. 22(8): p. 1139-1147.
- 31. Essandoh, K., et al., Blockade of exosome generation with GW4869 dampens the sepsis-induced inflammation and cardiac dysfunction. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 2015. 1852(11): p. 2362-2371.
- 32. Trajkovic, K., et al., Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science, 2008. 319(5867): p. 1244-1247.
- 33. Taverna, S., et al., Curcumin modulates chronic myelogenous leukemia exosomes composition and affects angiogenic phenotype via exosomal miR-21. Oncotarget, 2016. 7(21): p. 30420.
- 34. Alvarez-Erviti, L., et al., Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nature biotechnology, 2011. 29(4): p. 341-345.
Ayrıntılar
| Birincil Dil | Türkçe |
|---|---|
| Konular | Mühendislik |
| Bölüm | Makaleler |
| Yazarlar | |
| Proje Numarası | NA |
| Yayımlanma Tarihi | 22 Ekim 2021 |
| Yayımlandığı Sayı | Yıl 2021 Cilt: 14 Sayı: 1 |
Kaynak Göster
Bu eser Creative Commons Atıf 4.0 Uluslararası Lisansı ile lisanslanmıştır.