Critical Determinants of Extracellular Vesicle Stability for Enhanced Therapeutic Applications in Biotechnological Production
Main Article Content
Abstract
Paracrine factors play a central role in the regulation of cellular communication and function and serve as the primary agents in cell-based therapeutic interventions. These factors facilitate a wide range of critical physiological and pathological processes through diverse mechanisms, including secretion of soluble molecules, release of extracellular vesicles, and direct intercellular channel transfer. The study highlights the significant impact of stress-induced changes in extracellular vesicles on cellular responses. Several stressors, including temperature, and oxidative, mechanical, osmotic, and transportation stress, have been shown to alter the release and composition of extracellular vesicles in affected cells. Extracellular vesicle modifications can undermine the success of cell therapies by altering the paracrine activity of the delivered cells, although these cells retain their phenotypic characteristics. Therefore, a deeper understanding of the mechanisms that govern paracrine signaling and strategic modifications of this signaling are critical for improving the efficacy of cell therapy.
Article Details

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Copyright Transfer Statement
The copyright of this article is transferred to Current Applied Science and Technology journal with effect if and when the article is accepted for publication. The copyright transfer covers the exclusive right to reproduce and distribute the article, including reprints, translations, photographic reproductions, electronic form (offline, online) or any other reproductions of similar nature.
The author warrants that this contribution is original and that he/she has full power to make this grant. The author signs for and accepts responsibility for releasing this material on behalf of any and all co-authors.
Here is the link for download: Copyright transfer form.pdf
References
Abramowicz, A., Widłak, P., & Pietrowska, M. (2019). Different types of cellular stress affect the proteome composition of small extracellular vesicles: A mini review. Proteomes, 7(2), Article 23. https://doi.org/10.3390/proteomes7020023
Abyadeh, M., Mirshahvaladi, S., Kashani, S. A., Paulo, J. A., Amirkhani, A., Mehryab, F., Seydi, H., Moradpour, N., Jodeiryjabarzade, S., Mirzaei, M., Gupta, V., Shekari, F., & Salekdeh, G. H. (2024). Proteomic profiling of mesenchymal stem cell-derived extracellular vesicles: Impact of isolation methods on protein cargo. Journal of Extracellular Biology, 3(6), Article e159. https://doi.org/10.1002/jex2.159
Adamo, G., Picciotto, S., Gargano, P., Paterna, A., Raccosta, S., Rao, E., Romancino, D. P., Ghersi, G., Manno, M., Salamone M., & Bongiovanni, A., 2025. DetectEV: A functional enzymatic assay to assess integrity and bioactivity of extracellular vesicles. Journal of Extracellular Vesicles, 14(1), Article e70030. https://doi.org/10.1002/jev2.70030
Alexandre, L., Shen, M. L., de Araujo, L. O. F., Renault, J., DeCorwin-Martin, P., Martel, R., Ng, A., & Juncker, D. (2024). Effect of sample preprocessing and size-based extraction methods on the physical and molecular profiles of extracellular vesicles. ACS Sensors, 9(3), 1239-1251. https://doi.org/10.1021/acssensors.3c02070
Al-Kaabi, M. M., & AL-Rubai, A. J. F. (2021). Paracrine effects of Transplanted Neural stem cells in Ischemic strokes. Iraqi Journal of Cancer and Medical Genetics, 14(1), 29-35.
Arabi, L., Ho, J. Q., Javdani, N., Jones, S. M., Chen, I., Sharaf, M. H., Aieneravaie, M., Georgala, P., Sepand, M. R., Rafat, M., & Zanganeh, S. (2020). Nanoparticulate systems for sustained delivery of paracrine factors. In M. Mahmoudi (Ed). Nanomedicine for ischemic cardiomyopathy (pp. 157-169). Academic Press. https://doi.org/10.1016/B978-0-12-817434-0.00011-8
Aubertin, K., Piffoux, M., Sebbagh, A., Gauthier, J., Silva, A. K. A., & Gazeau, F. (2021). Applications thérapeutiques des vésicules extracellulaires. [Therapeutic applications of extracellular vesicles]. Médecine/Sciences, 37(12), 1146-1157. https://doi.org/10.1051/medsci/2021207
Ayers, L., Pink, R., Carter, D. R. F., & Nieuwland, R. (2019). Clinical requirements for extracellular vesicle assays. Journal of Extracellular Vesicles, 8(1), Article 1593755. https://doi.org/10.1080/20013078.2019.1593755
Aziz, A., & Larher, F. (1998). Osmotic stress induced changes in lipid composition &peroxidation in leaf discs of Brassica napus L. Journal of Plant Physiology, 153(5- 6), 754-762. https://doi.org/10.1016/S0176-1617(98)80231-9
Baek, G., Choi, H., Kim, Y., Lee, H. C., & Choi, C. (2019). Mesenchymal stem cell-derived extracellular vesicles as therapeutics and as a drug delivery platform. Stem Cells Translational Medicine, 8(9), 880-886. https://doi.org/10.1002/sctm.18-0226
Bağcı, C., Sever-Bahcekapili, M., Belder, N., Bennett, A. P., Erdener, Ş. E., & Dalkara, T. (2022). Overview of extracellular vesicle characterization techniques and introduction to combined reflectance and fluorescence confocal microscopy to distinguish extracellular vesicle subpopulations. Neurophotonics, 9(2), Article 021903. https://doi.org/10.1117/1.NPh.9.2.021903
Baranovskii, D. S., Klabukov, I. D., Arguchinskaya, N. V., Yakimova, A. O., Kisel, A. A., Yatsenko, E. M., Ivanov, S. A., Shegay, P. V., & Kaprin, A. D. (2022). Adverse events, side effects and complications in mesenchymal stromal cell-based therapies. Stem cell investigation, 9, 7. https://doi.org/10.21037/sci-2022-025.
Barron, A., May, G., Bremer, E., & Villarejo, M. (1986). Regulation of envelope protein composition during adaptation to osmotic stress in Escherichia coli. Journal of Bacteriology, 167(2), 433-438. https://doi.org/10.1128/jb.167.2.433-438.1986
Belliveau, J., & Papoutsakis, E. T. (2023). The microRNomes of Chinese hamster ovary (CHO) cells and their extracellular vesicles, and how they respond to osmotic and ammonia stress. Biotechnology and Bioengineering, 120(9), 2700-2716. https://doi.org/10.1002/bit.28356
Benedikter, B. J., Weseler, A. R., Wouters, E. F. M., Savelkoul, P. H. M., Rohde, G. G. U., & Stassen, F. R. M. (2018). Redox-dependent thiol modifications: implications for the release of extracellular vesicles. Cellular and Molecular Life Sciences, 75(13), 2321-2337. https://doi.org/10.1007/s00018-018-2806-z
Bewicke-Copley, F., Mulcahy, L. A., Jacobs, L. A., Samuel, P., Akbar, N., Pink, R. C., & Carter, D. R. F. (2017). Extracellular vesicles released following heat stress induce bystander effect in unstressed populations. Journal of Extracellular Vesicles, 6(1), Article 1340746. https://doi.org/10.1080/20013078.2017.1340746
Biasutto, L., Chiechi, A., Couch, R., Liotta, L. A., & Espina, V. (2013). Retinal pigment epithelium (RPE) exosomes contain signaling phosphoproteins affected by oxidative stress. Experimental Cell Research, 319(13), 2113-2123. https://doi.org/10.1016/j.yexcr.2013.05.005
Bister, N., Pistono, C., Huremagic, B., Jolkkonen, J., Giugno, R., & Malm, T. (2020). Hypoxia and extracellular vesicles: A review on methods, vesicular cargo and functions. Journal of Extracellular Vesicles, 10(1), Article e12002. https://doi.org/10.1002/jev2.12002
Bonsergent, É., Bui, S., & Lavieu, G. (2022). Quantitative measurement of extracellular vesicle content delivery within acceptor cells. Methods in Molecular Biology, 2473, 397- 403. https://doi.org/10.1007/978-1-0716-2209-4_25
Brennan, K., Martin, K., FitzGerald, S. P., O'Sullivan, J., Wu, Y., Blanco, A., Richardson, C., & Mc Gee, M. M. (2020). A comparison of methods for the isolation and separation of extracellular vesicles from protein and lipid particles in human serum. Scientific Reports, 10(1), Article 1039. https://doi.org/10.1038/s41598-020-57497-7
Buschmann, D., Mussack, V., & Byrd, J. B. (2021). Separation, characterization, and standardization of extracellular vesicles for drug delivery applications. Advanced Drug Delivery Reviews, 174, 348-368. https://doi.org/10.1016/j.addr.2021.04.027
Cai, J., Wu, J., Wang, J., Li, Y., Hu, X., Luo, S., & Xiang, D. (2020). Extracellular vesicles derived from different sources of mesenchymal stem cells: therapeutic effects and translational potential. Cell and Bioscience, 10, Article 69. https://doi.org/10.1186/s13578-020-00427-x
Camacho, V., Toxavidis, V., & Tigges, J. C. (2017). Characterization of extracellular vesicles by flow cytometry. Methods in Molecular Biology, 1660, 175-190. https://doi.org/10.1007/978-1-4939-7253-1_14
Cesi, G., Walbrecq, G., Margue, C., & Kreis, S. (2016). Transferring intercellular signals and traits between cancer cells: extracellular vesicles as "homing pigeons". Cell Communication and Signaling, 14(1), Article 13. https://doi.org/10.1186/s12964-016-0136-z
Cheng, K., & Kalluri, R. (2023). Guidelines for clinical translation and commercialization of extracellular vesicles and exosomes based therapeutics. Extracellular Vesicle, 2, Article 100029. https://doi.org/10.1016/j.vesic.2023.100029
Cheng, X.-M., Hu, Y.-Y., Yang, T., Wu, N., & Wang, X.-N. (2022). Reactive oxygen species and oxidative stress in vascular-related diseases. Oxidative Medicine and Cellular Longevity, 2022, Article 7906091. https://doi.org/10.1155/2022/7906091
Chiaradia, E., Tancini, B., Emiliani, C., Delo, F., Pellegrino, R. M., Tognoloni, A., Urbanelli, L., & Buratta, S. (2021). Extracellular vesicles under oxidative stress conditions: Biological properties and physiological roles. Cells, 10(7), Article 1763. https://doi.org/10.3390/cells10071763
Chua, J. K., Lim, J. W., Foong, L. H., Mok, C. Y., Tan, H. Y., Tung, X. Y., Ramasamy, T. S., Govindasamy, V., Then, K. Y., Das, A. K., & Cheong, S. K. (2022). Mesenchymal stem cell-derived extracellular vesicles: Progress and remaining hurdles in developing regulatory compliant quality control assays. Advances in Experimental Medicine and Biology, 1401, 191- 211. https://doi.org/10.1007/5584_2022_728
Clark, D., & Parker, J. (1984). Proteins induced by high osmotic pressure in Escherichia coli. FEMS Microbiology Letters, 25(1), 81-83.
Clayton, A., Turkes, A., Navabi, H., Mason, M. D., & Tabi, Z. (2005). Induction of heat shock proteins in B-cell exosomes. Journal of Cell Science, 118(Pt 16), 3631-3638. https://doi.org/10.1242/jcs.02494
Clos-Sansalvador, M., Monguió-Tortajada, M., Roura, S., Franquesa, M., & Borràs, F. E. (2022). Commonly used methods for extracellular vesicles' enrichment: Implications in downstream analyses and use. European Journal of Cell Biology, 101(3), Article 151227. https://doi.org/10.1016/j.ejcb.2022.151227
Colao, I. L., Corteling, R., Bracewell, D., & Wall, I. (2018). Manufacturing exosomes: A promising therapeutic platform. Trends in Molecular Medicine, 24(3), 242-256. https://doi.org/10.1016/j.molmed.2018.01.006
Davies, O. & Rafiq, Q. (2017). Considerations for the bioprocessing, manufacture and translation of extracellular vesicles for therapeutic applications. Cell and Gene Therapy Insights, 3(6), 683-694. https://doi.org/10.18609/cgti.2017.066
de Jager, T. L., Cockrell, A. E., & Du Plessis, S. S. (2017). Ultraviolet light induced generation of reactive oxygen species. Advances in Experimental Medicine and Biology, 996, 15-23. https://doi.org/10.1007/978-3-319-56017-5_2
Du, S., Guan, Y., Xie, A., Yan, Z., Gao, S., Li, W., Rao, L., Chen, X., & Chen, T. (2023). Extracellular vesicles: a rising star for therapeutics and drug delivery. Journal of Nanobiotechnology, 21(1), Article 231. https://doi.org/10.1186/s12951-023-01973-5
Edelmann, M. J., & Kima, P. E. (2022). Current understanding of extracellular vesicle homing/tropism. Zoonoses, 2, Article 14. https://doi.org/10.15212/zoonoses-2022-0004
Eldh, M., Ekström, K., Valadi, H., Sjöstrand, M., Olsson, B., Jernås, M., & Lötvall, J. (2010). Exosomes communicate protective messages during oxidative stress; possible role of exosomal shuttle RNA. PloS One, 5(12), Article e15353. https://doi.org/10.1371/journal.pone.0015353
Etheridge, A., Gomes, C. P., Pereira, R. W., Galas, D., & Wang, K. (2013). The complexity, function and applications of RNA in circulation. Frontiers in Genetics, 4, Article 115. https://doi.org/10.3389/fgene.2013.00115
Félix, L. M., Vidal, A. M., Serafim, C., Valentim, A. M., Antunes, L. M., Campos, S., Matos, M., Monteiro, S. M., & Coimbra, A. M. (2016). Ketamine-induced oxidative stress at different developmental stages of zebrafish (Danio rerio) embryos. RSC Advances, 6, 61254-61266. https://doi.org/10.1039/C6RA08298J
Ferraris V. A. (2016). How do cells talk to each other?: Paracrine factors secreted by mesenchymal stromal cells. The Journal of Thoracic and Cardiovascular Surgery, 151(3), 849-851. https://doi.org/10.1016/j.jtcvs.2015.11.035
Flower, T.R., Pulsipher, V., & Moreno, A. (2015). A new tool in regenerative medicine: mesenchymal stem cell secretome. Journal of Stem Cell Research and Therapeutics, 1(1), 22-24. https://doi.org/10.15406/jsrt.2015.01.00005
Fontaine, M. J., Shih, H., Schäfer, R., & Pittenger, M. F. (2016). Unraveling the mesenchymal stromal cells' paracrine immunomodulatory effects. Transfusion Medicine Reviews, 30(1), 37-43. https://doi.org/10.1016/j.tmrv.2015.11.004
Gámez-Valero, A., Monguió-Tortajada, M., Carreras-Planella, L., Franquesa, M. l, Beyer, K., & Borràs, F. E. (2016). Size-exclusion chromatography-based isolation minimally alters extracellular vesicles' characteristics compared to precipitating agents. Scientific Reports, 6, Article 33641. https://doi.org/10.1038/srep33641
Gandham, S., Su, X., Wood, J., Nocera, A. L., Alli, S. C., Milane, L. S., Zimmerman, A. J., Amiji, M. M., & Ivanov, A. R. (2020). Technologies and standardization in research on extracellular vesicles. Trends in Biotechnology, 38, 1066-1098.
Gardiner, C., Di Vizio, D., Sahoo, S., Théry, C., Witwer, K. W., Wauben, M., & Hill, A. F. (2016). Techniques used for the isolation and characterization of extracellular vesicles: results of a worldwide survey. Journal of Extracellular Vesicles, 5, Article 32945. https://doi.org/10.3402/jev.v5.32945
Gebremedhn, S., Gad, A., Aglan, H. S., Laurincik, J., Prochazka, R., Salilew-Wondim, D., Hoelker, M., Schellander, K., & Tesfaye, D. (2020). Extracellular vesicles shuttle protective messages against heat stress in bovine granulosa cells. Scientific Reports, 10(1), Article 15824. https://doi.org/10.1038/s41598-020-72706-z
Gimona, M., Pachler, K., Laner-Plamberger, S., Schallmoser, K., & Rohde, E. (2017). Manufacturing of human extracellular vesicle-based therapeutics for clinical use. International Journal of Molecular Sciences, 18(6), Article 1190. https://doi.org/10.3390/ijms18061190
Ginini, L., Billan, S., Fridman, E., & Gil, Z. (2022). Insight into extracellular vesicle-cell communication: From cell recognition to intracellular fate. Cells, 11(9), Article 1375. https://doi.org/10.3390/cells11091375
Glembotski C. C. (2017). Expanding the paracrine hypothesis of stem cell-mediated repair in the heart: When the unconventional becomes conventional. Circulation Research, 120(5), 772-774. https://doi.org/10.1161/CIRCRESAHA.116.310298
Grangier, A., Branchu, J., Volatron, J., Piffoux, M., Gazeau, F., Wilhelm, C., & Silva, A. K. A. (2021). Technological advances towards extracellular vesicles mass production. Advanced Drug Delivery Reviews, 176, Article 113843. https://doi.org/10.1016/j.addr.2021.113843
Greening, D. W., Gopal, S. K., Xu, R., Simpson, R. J., & Chen, W. (2015). Exosomes and their roles in immune regulation and cancer. Seminars in Cell and Developmental Biology, 40, 72-81. https://doi.org/10.1016/j.semcdb.2015.02.009
Gualerzi, A., Kooijmans, S. A. A., Niada, S., Picciolini, S., Brini, A. T., Camussi, G., & Bedoni, M. (2019). Raman spectroscopy as a quick tool to assess purity of extracellular vesicle preparations and predict their functionality. Journal of extracellular vesicles, 8(1), Article 1568780. https://doi.org/10.1080/20013078.2019.1568780
Gudbergsson, J. M., Johnsen, K. B., Skov, M. N., & Duroux, M. (2016). Systematic review of factors influencing extracellular vesicle yield from cell cultures. Cytotechnology, 68(4), 579-592. https://doi.org/10.1007/s10616-015-9913-6
Guisbert, E., Czyz, D. M., Richter, K., McMullen, P. D., & Morimoto, R. I. (2013). Identification of a tissue-selective heat shock response regulatory network. PLoS Genetics, 9(4), Article e1003466. https://doi.org/10.1371/journal.pgen.1003466
Ha, D. H., Kim, H. K., Lee, J., Kwon, H. H., Park, G. H., Yang, S. H., Jung, J. Y., Choi, H., Lee, J. H., Sung, S., Yi, Y. W., & Cho, B. S. (2020). Mesenchymal stem/stromal cell-derived exosomes for immunomodulatory therapeutics and skin regeneration. Cells, 9(5), Article 1157. https://doi.org/10.3390/cells9051157
Hedlund, M., Nagaeva, O., Kargl, D., Baranov, V., & Mincheva-Nilsson, L. (2011). Thermal- and oxidative stress causes enhanced release of NKG2D ligand-bearing immunosuppressive exosomes in leukemia/lymphoma T and B cells. PloS One, 6(2), Article e16899. https://doi.org/10.1371/journal.pone.0016899
Huang, C., Neupane, Y. R., Lim, X. C., Shekhani, R., Czarny, B., Wacker, M. G., Pastorin, G., & Wang, J. W. (2021). Extracellular vesicles in cardiovascular disease. Advances in Clinical Chemistry, 103, 47-95. https://doi.org/10.1016/bs.acc.2020.08.006
Ingato, D., Lee, J. U., Sim, S. J., & Kwon, Y. J. (2016). Good things come in small packages: Overcoming challenges to harness extracellular vesicles for therapeutic delivery. Journal of Controlled Release, 241, 174-185. https://doi.org/10.1016/j.jconrel.2016.09.016
Jin, Y., Chen, K., Wang, Z., Wang, Y., Liu, J., Lin, L., Shao, Y., Gao, L., Yin, H., Cui, C., Tan, Z., Liu, L., Zhao, C., Zhang, G., Jia, R., Du, L., Chen, Y., Liu, R., Xu, J., Hu, X., & Wang, Y. (2016). DNA in serum extracellular vesicles is stable under different storage conditions. BMC Cancer, 16(1), Article 753. https://doi.org/10.1186/s12885-016-2783-2
Joshi, B. S., de Beer, M. A., Giepmans, B. N. G., & Zuhorn, I. S. (2020). Endocytosis of extracellular vesicles and release of their cargo from endosomes. ACS Nano, 14(4), 4444-4455. https://doi.org/10.1021/acsnano.9b10033
Kefaloyianni, E. (2022). Soluble forms of cytokine and growth factor receptors: mechanisms of generation and modes of action in the regulation of local and systemic inflammation. FEBS Letters, 596(5), 589-606. https://doi.org/10.1002/1873-3468.14305
Keshtkar, S., Azarpira, N., & Ghahremani, M. H. (2018). Mesenchymal stem cell-derived extracellular vesicles: novel frontiers in regenerative medicine. Stem Cell Research and Therapy, 9(1), Article 63. https://doi.org/10.1186/s13287-018-0791-7
Khawar, M. B., Abbasi, M. H., Siddique, Z., Arif, A., & Sheikh, N. (2019). An update on novel therapeutic warfronts of extracellular vesicles (evs) in cancer treatment: Where we are standing right now and where to go in the future. Oxidative Medicine and Cellular Longevity, 2019, Article 9702562. https://doi.org/10.1155/2019/9702562
Klabukov, I., Atiakshin, D., Kogan, E., Ignatyuk, M., Krasheninnikov, M., Zharkov, N., Yakimova, A., Grinevich, V., Pryanikov, P., Parshin, V., Sosin, D., Kostin, A. A., Shegay, P., Kaprin, A. D., & Baranovskii, D. (2023a). Post-Implantation Inflammatory Responses to Xenogeneic Tissue-Engineered Cartilage Implanted in Rabbit Trachea: The Role of Cultured Chondrocytes in the Modification of Inflammation. International Journal of Molecular Sciences, 24(23), 16783. https://doi.org/10.3390/ijms242316783.
Klabukov, I. D., Baranovskii, D. S., Shegay, P. V., & Kaprin, A. D. (2023b). Pitfalls and promises of bile duct alternatives: There is plenty of room in the regenerative surgery. World Journal of Gastroenterology, 29(30), 4701-4705. https://doi.org/10.3748/wjg.v29.i30.4701.
Klabukov, I., Tenchurin, T., Shepelev, A., Baranovskii, D., Mamagulashvili, V., Dyuzheva, T., Krasilnikova, O., Balyasin, M., Lyundup, A., Krasheninnikov, M., Sulina, Y., Gomzyak, V., Krasheninnikov, S., Buzin, A., Zayratyants, G., Yakimova, A., Demchenko, A., Ivanov, S., Shegay, P., Kaprin, A., & Chvalun, S. (2023c). Biomechanical Behaviors and Degradation Properties of Multilayered Polymer Scaffolds: The Phase Space Method for Bile Duct Design and Bioengineering. Biomedicines, 11(3), 745. https://doi.org/10.3390/biomedicines11030745.
Konoshenko, M. Y., Lekchnov, E. A., Vlassov, A. V., & Laktionov, P. P. (2018). Isolation of extracellular vesicles: General methodologies and latest trends. BioMed Research International, 2018, Article 8545347. https://doi.org/10.1155/2018/8545347
Korchak, J. A., Wiest, E. F., & Zubair, A. C. (2023). How do we assess batch-to-batch consistency between extracellular vesicle products? Transfusion, 63(2), 279-287. https://doi.org/10.1111/trf.17156
Krasilnikova, O. A., Baranovskii, D. S., Lyundup, A. V., Shegay, P. V., Kaprin, A. D., & Klabukov, I. D. (2022a). Stem and Somatic Cell Monotherapy for the Treatment of Diabetic Foot Ulcers: Review of Clinical Studies and Mechanisms of Action. Stem cell reviews and reports, 18(6), 1974-1985. https://doi.org/10.1007/s12015-022-10379-z.
Krasilnikova, O. A., Baranovskii, D. S., Yakimova, A. O., Arguchinskaya, N., Kisel, A., Sosin, D., Sulina, Y., Ivanov, S. A., Shegay, P. V., Kaprin, A. D., & Klabukov, I. D. (2022b). Intraoperative Creation of Tissue-Engineered Grafts with Minimally Manipulated Cells: New Concept of Bone Tissue Engineering In Situ. Bioengineering (Basel, Switzerland), 9(11), 704. https://doi.org/10.3390/bioengineering9110704.
Krasilnikova, O., Yakimova, A., Ivanov, S., Atiakshin, D., Kostin, A. A., Sosin, D., Shegay, P., Kaprin, A. D., & Klabukov, I. (2023). Gene-activated materials in regenerative dentistry: narrative review of technology and study results. International Journal of Molecular Sciences, 24(22), 16250. https://doi.org/10.3390/ijms242216250.
Kusuma, G. D., Barabad,i M., Tan J. L., Morton, D. A. V., Frith, J. E., & Lim, R. (2018). To protect and to preserve: Novel preservation strategies for extracellular vesicles. Frontiers in Pharmacology, 9, Article 1199. https://doi.org/10.3389/fphar.2018.01199
Kulakov, A., Kogan, E., Brailovskaya, T., Vedyaeva, A., Zharkov, N., Krasilnikova, O., Krasheninnikov, M., Baranovskii, D., Rasulov, T., & Klabukov, I. (2021). Mesenchymal Stromal Cells Enhance Vascularization and Epithelialization within 7 Days after Gingival Augmentation with Collagen Matrices in Rabbits. Dentistry journal, 9(9), 101. https://doi.org/10.3390/dj9090101.
Kumar, P. L., Kandoi, S., Misra, R., S., V., K., R., & Verma, R. S. (2019). The mesenchymal stem cell secretome: A new paradigm towards cell-free therapeutic mode in regenerative medicine. Cytokine and Growth Factor Reviews, 46, 1-9. https://doi.org/10.1016/j.cytogfr.2019.04.002
Lacroix, R., Judicone, C., Poncelet, P., Robert, S., Arnaud, L., Sampol, J., & Dignat-George, F. (2012). Impact of pre-analytical parameters on the measurement of circulating microparticles: towards standardization of protocol. Journal of Thrombosis and Haemostasis, 10(3), 437-446. https://doi.org/10.1111/j.1538-7836.2011.04610.x
Laggner, M., Gugerell, A., Bachmann, C., Hofbauer, H., Vorstandlechner, V., Seibold, M., Lechner, G. G., Peterbauer, A., Madlener, S., Demyanets, S., Sorgenfrey, D., Ostler, T., Erb, M., Mildner, M., & Ankersmit, H. J. (2020). Reproducibility of GMP-compliant production of therapeutic stressed peripheral blood mononuclear cell-derived secretomes, a novel class of biological medicinal products. Stem Cell Research and Therapy, 11(1), Article 9. https://doi.org/10.1186/s13287-019-1524-2
Lancaster, G. I., & Febbraio, M. A. (2005). Exosome-dependent trafficking of HSP70: a novel secretory pathway for cellular stress proteins. The Journal of Biological Chemistry, 280(24), 23349-23355. https://doi.org/10.1074/jbc.M502017200
Lee, M., Ban, J.-J., Im, W. & Kim, M. (2016). Influence of storage condition on exosome recovery. Biotechnology and Bioprocess Engineering, 21, 299-304. https://doi.org/10.1007/s12257-015-0781-x
Lefebvre, F. A., & Lécuyer, E. (2017). Small luggage for a long journey: Transfer of vesicle-enclosed small RNA in interspecies communication. Frontiers in Microbiology, 8, Article 377. https://doi.org/10.3389/fmicb.2017.00377
Legrand, J. M. D., & Martino, M. M. (2022). Growth factor and cytokine delivery systems for wound healing. Cold Spring Harbor Perspectives in Biology, 14(8), Article a041234. https://doi.org/10.1101/cshperspect.a041234
Li, S., Xu, J., Qian, J., & Gao, X., (2020). Engineering extracellular vesicles for cancer therapy: recent advances and challenges in clinical translation. Biomaterials Science, 8(24), 6978-6991. https://doi.org/10.1039/d0bm01385d
Liang, X., Ding, Y., Zhang, Y., Tse, H. F., & Lian, Q. (2014). Paracrine mechanisms of mesenchymal stem cell-based therapy: current status and perspectives. Cell Transplantation, 23(9), 1045-1059. https://doi.org/10.3727/096368913X667709
Liangsupree, T., Multia, E., & Riekkola, M.-L. (2021). Modern isolation and separation techniques for extracellular vesicles. Journal of Chromatography A, 1636, Article 461773. https://doi.org/10.1016/j.chroma.2020.461773
Linares, R., Tan, S., Gounou, C., Arraud, N., & Brisson, A. R. (2015). High-speed centrifugation induces aggregation of extracellular vesicles. Journal of Extracellular Vesicles, 4, Article 29509. https://doi.org/10.3402/jev.v4.29509
Liu, S., Zhou, J., Zhang, X., Liu, Y., Chen, J., Hu, B., Song, J., & Zhang, Y. (2016). Strategies to optimize adult stem cell therapy for tissue regeneration. International Journal of Molecular Sciences, 17(6), Article 982. https://doi.org/10.3390/ijms17060982
Lopatina, T., Widera, D., & Efimenko, A. (2022). Editorial: Extracellular RNAs as outside regulators of gene expression in homeostasis and pathology. Frontiers in Cell and Developmental Biology, 9, Article 818430. https://doi.org/10.3389/fcell.2021.818430
Lyamina, S., Baranovskii, D., Kozhevnikova, E., Ivanova, T., Kalish, S., Sadekov, T., Klabukov, I., Maev, I., & Govorun, V. (2023). Mesenchymal stromal cells as a driver of inflammaging. International Journal of Molecular Sciences, 24(7), Article 6372. https://doi.org/10.3390/ijms24076372
Maas, S. L. N., Breakefield, X. O., & Weaver, A. M. (2017). Extracellular vesicles: Unique intercellular delivery vehicles. Trends in Cell Biology, 27(3), 172-188. https://doi.org/10.1016/j.tcb.2016.11.003
Mabotuwana, N. S., Rech, L., Lim, J., Hardy, S. A., Murtha, L. A., Rainer, P. P., & Boyle, A. J. (2022). Paracrine factors released by stem cells of mesenchymal origin and their effects in cardiovascular disease: A systematic review of pre-clinical studies. Stem Cell Reviews and Reports, 18(8), 2606-2628. https://doi.org/10.1007/s12015-022-10429-6
Magnadóttir, B., Uysal-Onganer, P., Kraev, I., Svansson, V., Hayes, P., & Lange, S. (2020). Deiminated proteins and extracellular vesicles - Novel serum biomarkers in whales and orca. Comparative Biochemistry and Physiology. Part D: Genomics and Proteomics, 34, Article 100676. https://doi.org/10.1016/j.cbd.2020.100676
Mahmood, A., Otruba, Z., Weisgerber, A. W., Palay, M. D., Nguyen, M. T., Bills, B. L., & Knowles, M. K. (2023). Exosome secretion kinetics are controlled by temperature. Biophysical Journal, 122(7), 1301-1314. https://doi.org/10.1016/j.bpj.2023.02.025
Maksimova, N. V., Michenko, A. V., Krasilnikova, O. A., Klabukov, I. D., Gadaev, I. Y., Krasheninnikov, M. E., Belkov, P. A., & Lyundup, A. V. (2022). Mesenchymal stromal cell therapy alone does not lead to complete restoration of skin parameters in diabetic foot patients within a 3-year follow-up period. BioImpacts, 12(1), 51-55. https://doi.org/10.34172/bi.2021.22167
Mannerström, B., Kaur, S., & Seppänen-Kaijansinkko, R. (2019). Cells. In R. Seppänen-Kaijansinkko (Eds.) Tissue engineering in oral and maxillofacial surgery (pp. 27-33). Springer. https://doi.org/10.1007/978-3-030-24517-7_3
Martins, T. S., Catita, J., Rosa, I. M., Silva, O. A. B. D. C. E., & Henriques, A. G. (2018). Exosome isolation from distinct biofluids using precipitation and column-based approaches. PloS One, 13(6), Article e0198820. https://doi.org/10.1371/journal.pone.0198820
Mas-Bargues, C., & Borrás, C. (2021). Importance of stem cell culture conditions for their derived extracellular vesicles therapeutic effect. Free Radical Biology and Medicine, 168, 16-24. https://doi.org/10.1016/j.freeradbiomed.2021.03.028
Mas-Bargues, C., Sanz-Ros, J., Romero-García, N., Huete-Acevedo, J., Dromant, M., & Borrás, C. (2023). Small extracellular vesicles from senescent stem cells trigger adaptive mechanisms in young stem cells by increasing antioxidant enzyme expression. Redox Biology, 62, Article 102668. https://doi.org/10.1016/j.redox.2023.102668
Matsuda, M., & Shimomura, I. (2013). Increased oxidative stress in obesity: implications for metabolic syndrome, diabetes, hypertension, dyslipidemia, atherosclerosis, and cancer. Obesity Research and Clinical Practice, 7(5), e330-e341. https://doi.org/10.1016/j.orcp.2013.05.004
Melling, G. E., Carollo, E., Conlon, R., Simpson, J. C., & Carter, D. R. F. (2019). The challenges and possibilities of extracellular vesicles as therapeutic vehicles. European Journal of Pharmaceutics and Biopharmaceutics, 144, 50-56. https://doi.org/10.1016/j.ejpb.2019.08.009
Nathan, C., & Cunningham-Bussel, A. (2013). Beyond oxidative stress: an immunologist's guide to reactive oxygen species. Nature reviews. Immunology, 13(5), 349-361. https://doi.org/10.1038/nri3423
Nelson, B. C., Maragh, S., Ghiran, I. C., Jones, J. C., DeRose, P. C., Elsheikh, E., Vreeland, W. N., & Wang, L. (2020). Measurement and standardization challenges for extracellular vesicle therapeutic delivery vectors. Nanomedicine, 15(22), 2149-2170. https://doi.org/10.2217/nnm-2020-0206
Neves-da-Rocha, J., Santos-Saboya, M. J., Lopes, M. E. R., Rossi, A., & Martinez-Rossi, N. M. (2023). Insights and perspectives on the role of proteostasis and heat shock proteins in fungal infections. Microorganisms, 11(8), Article 1878. https://doi.org/10.3390/microorganisms11081878
Ng, K. S., Smith, J. A., McAteer, M. P., Mead, B. E., Ware, J., Jackson, F. O., Carter, A., Ferreira, L., Bure, K., Rowley, J. A., Reeve, B., Brindley, D. A., & Karp, J. M. (2019). Bioprocess decision support tool for scalable manufacture of extracellular vesicles. Biotechnology and Bioengineering, 116(2), 307-319. https://doi.org/10.1002/bit.26809
Nguyen, V. V. T., Witwer, K. W., Verhaar, M. C., Strunk, D., & van Balkom, B. W. M. (2020). Functional assays to assess the therapeutic potential of extracellular vesicles. Journal of Extracellular Vesicles, 10(1), Article e12033. https://doi.org/10.1002/jev2.12033
Niedzielska, E., Smaga, I., Gawlik, M., Moniczewski, A., Stankowicz, P., Pera, J., & Filip, M. (2016). Oxidative stress in neurodegenerative diseases. Molecular Neurobiology, 53(6), 4094-4125. https://doi.org/10.1007/s12035-015-9337-5
Nolte-'t Hoen, E. (2018). Putting EV into context: contextual factors influencing immune-related functions of extracellular vesicles (EV). Seminars in Immunopathology, 40(5), 421-424. https://doi.org/10.1007/s00281-018-0720-y
Nooshabadi, V. T., Mardpour, S., Yousefi-Ahmadipour, A., Allahverdi, A., Izadpanah, M., Daneshimehr, F., Ai, J., Banafshe, H. R., & Ebrahimi-Barough, S. (2018). The extracellular vesicles-derived from mesenchymal stromal cells: A new therapeutic option in regenerative medicine. Journal of Cellular Biochemistry, 119(10), 8048-8073. https://doi.org/10.1002/jcb.26726
O'Brien, K., Ughetto, S., Mahjoum, S., Nair, A. V., & Breakefield, X. O. (2022). Uptake, functionality, and re-release of extracellular vesicle-encapsulated cargo. Cell Reports, 39(2), Article 110651. https://doi.org/10.1016/j.celrep.2022.110651
O'Neill, C. P., Gilligan, K. E., & Dwyer, R. M. (2019). Role of extracellular vesicles (EVs) in cell stress response and resistance to cancer therapy. Cancers, 11(2), Article 136. https://doi.org/10.3390/cancers11020136
Paganini, C., Palmiero, U. C., Pocsfalvi, G., Touzet, N., Bongiovanni, A., & Arosio, P. (2019). Scalable production and isolation of extracellular vesicles: Available sources and lessons from current industrial bioprocesses. Biotechnology Journal, 14(10), Article e1800528. https://doi.org/10.1002/biot.201800528
Palanisamy, C. P., Pei, J., Alugoju, P., Anthikapalli, N. V. A., Jayaraman, S., Veeraraghavan, V. P., Gopathy, S., Roy, J. R., Janaki, C. S., Thalamati, D., Mironescu, M., Luo, Q., Miao, Y., Chai, Y., & Long, Q. (2023). New strategies of neurodegenerative disease treatment with extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs). Theranostics, 13(12), 4138-4165. https://doi.org/10.7150/thno.83066
Park, S. J., Jeon, H., Yoo, S.-M., & Lee, M.-S. (2018). The effect of storage temperature on the biological activity of extracellular vesicles for the complement system. In Vitro Cellular and Developmental Biology-Animal, 54(6), 423-429. https://doi.org/10.1007/s11626-018-0261-7
Patel, U., Susman, D., & Allan, A. L. (2024). Quality control and validation of extracellular vesicles isolated from cultured human breast cancer cells. BMC Research Notes, 17(1), Article 202. https://doi.org/10.1186/s13104-024-06865-x
Phelps, J., Sanati-Nezhad, A., Ungrin, M., Duncan, N. A., & Sen, A. (2018). Bioprocessing of mesenchymal stem cells and their derivatives: Toward cell-free therapeutics. Stem Cells International, 2018, Article 9415367. https://doi.org/10.1155/2018/9415367
Plotnikov, E. Y., Silachev, D. N., Popkov, V. A., Zorova, L. D., Pevzner, I. B., Zorov, S. D., Jankauskas, S. S., Babenko, V. A., Sukhikh, G. T., & Zorov, D. B. (2017). Intercellular signalling cross-talk: To kill, to heal and to rejuvenate. Heart, Lung and Circulation, 26(7), 648-659. https://doi.org/10.1016/j.hlc.2016.12.002
Qin, Y., Long, L., & Huang, Q. (2020). Extracellular vesicles in toxicological studies: key roles in communication between environmental stress and adverse outcomes. Journal of Applied Toxicology, 40(9), 1166-1182. https://doi.org/10.1002/jat.3963
Rafieezadeh, D., & Rafieezadeh, A. (2024). Extracellular vesicles and their therapeutic applications: a review article (part 1). International Journal of Physiology, Pathophysiology and Pharmacology, 16(1), 1- 9. https://doi.org/10.62347/QPAG5693
Ragusa, A. (2023). Secondary metabolites for the reduction of oxidative stress. Molecules, 28(22), Article 7555. https://doi.org/10.3390/molecules28227555
Rai, A., Claridge, B., Lozano, J., & Greening, D. W. (2024). The discovery of extracellular vesicles and their emergence as a next-generation therapy. Circulation Research, 135(1), 198-221. https://doi.org/10.1161/CIRCRESAHA.123.323054
Rasmussen, R. N., Christensen, K. V., Holm, R. & Nielsen, C. U., (2019). Transcriptome analysis identifies activated signaling pathways and regulated ABC transporters and solute carriers after hyperosmotic stress in renal MDCK I cells. Genomics, 111(6), 1557-1565. https://doi.org/10.1016/j.ygeno.2018.10.014
Rayamajhi, S., Sulthana, S., Ferrel, C., Shrestha, T. B., & Aryal, S. (2023). Extracellular vesicles production and proteomic cargo varies with incubation time and temperature. Experimental Cell Research, 422(2), Article 113454. https://doi.org/10.1016/j.yexcr.2022.113454
Rezaie, J., Feghhi, M., & Etemadi, T. (2022). A review on exosomes application in clinical trials: perspective, questions, and challenges. Cell Communication and Signaling, 20(1), Article 145. https://doi.org/10.1186/s12964-022-00959-4
Ridiandries, A., Tan, J. T. M., & Bursill, C. A. (2018). The role of chemokines in wound healing. International Journal of Molecular Sciences, 19(10), Article 3217. https://doi.org/10.3390/ijms19103217
Rissland, O. S. (2017). The organization and regulation of mRNA-protein complexes. Wiley Interdisciplinary Reviews RNA, 8(1), Article e1369. https://doi.org/10.1002/wrna.1369
Royo, F., Théry, C., Falcón-Pérez, J. M., Nieuwland, R., & Witwer, K. W. (2020). Methods for separation and characterization of extracellular vesicles: Results of a worldwide survey performed by the ISEV rigor and standardization subcommittee. Cells, 9(9), Article 1955. https://doi.org/10.3390/cells9091955
Salmond, N., & Williams, K. C. (2021). Isolation and characterization of extracellular vesicles for clinical applications in cancer - time for standardization? Nanoscale Advances, 3(7), 1830- 1852. https://doi.org/10.1039/d0na00676a
Schulz, E., Karagianni, A., Koch, M., & Fuhrmann, G. (2020). Hot EVs - How temperature affects extracellular vesicles. European Journal of Pharmaceutics and Biopharmaceutics, 146, 55- 63. https://doi.org/10.1016/j.ejpb.2019.11.010
Shao, H., Im, H., Castro, C. M., Breakefield, X., Weissleder, R., & Lee, H. (2018). New Technologies for Analysis of Extracellular Vesicles. Chemical Reviews, 118(4), 1917- 1950. https://doi.org/10.1021/acs.chemrev.7b00534
Sheta, M., Taha, E. A., Lu, Y., & Eguchi, T. (2023). Extracellular vesicles: New classification and tumor immunosuppression. Biology, 12(1), Article 110. https://doi.org/10.3390/biology12010110
Simonsen, J. B. (2017). What are we looking at? Extracellular vesicles, lipoproteins, or both? Circulation Research, 121(8), 920-922. https://doi.org/10.1161/CIRCRESAHA.117.311767
Singh, M. K., Shin, Y., Ju, S., Han, S., Choe, W., Yoon, K. S., Kim, S. S., & Kang, I. (2024). Heat shock response and heat shock proteins: Current understanding and future opportunities in human diseases. International Journal of Molecular Sciences, 25(8), Article 4209. https://doi.org/10.3390/ijms25084209
Sivanantham, A., & Jin, Y. (2022). Impact of storage conditions on EV integrity/surface markers and cargos. Life, 12(5), Article 697. https://doi.org/10.3390/life12050697
Smirnova, A., Yatsenko, E., Baranovskii, D., & Klabukov, I. (2023). Mesenchymal stem cell-derived extracellular vesicles in skin wound healing: the risk of senescent drift induction in secretome-based therapeutics. Military Medical Research, 10(1), Article 60. https://doi.org/10.1186/s40779-023-00498-0
Stawarska, A., Bamburowicz-Klimkowska, M., Runden-Pran, E., Dusinska, M., Cimpan, M. R., Rios-Mondragon, I., & Grudzinski, I. P. (2024). Extracellular vesicles as next-generation diagnostics and advanced therapy medicinal products. International Journal of Molecular Sciences, 25(12), Article 6533. https://doi.org/10.3390/ijms25126533
Syromiatnikova, V., Prokopeva, A., & Gomzikova, M. (2022). Methods of the Large-Scale Production of Extracellular Vesicles. International Journal of Molecular Sciences, 23(18), Article 10522. https://doi.org/10.3390/ijms231810522
Tachibana, A., Santoso, M. R., Mahmoudi, M., Shukla, P., Wang, L., Bennett, M., Goldstone, A. B., Wang, M., Fukushi, M., Ebert, A. D., Woo, Y. J., Rulifson, E., & Yang, P. C. (2017). Paracrine effects of the pluripotent stem cell-derived cardiac myocytes salvage the injured myocardium. Circulation Research, 121(6), e22-e36. https://doi.org/10.1161/CIRCRESAHA.117.310803
Takasugi, M., Okada, R., Takahashi, A., Chen, D. V., Watanabe, S., & Hara, E. (2017). Small extracellular vesicles secreted from senescent cells promote cancer cell proliferation through EphA2. Nature Communications, 8, Article 15729. https://doi.org/10.1038/ncomms15728
Tang, P., Song, F., Chen, Y., Gao, C., Ran, X., Li, Y., Сhen, Z., Zhang, Z., Wei, W., Peng, Z., Li, Z., & Zhou, C. (2024). Preparation and characterization of extracellular vesicles and their cutting-edge applications in regenerative medicine. Applied Materials Today, 37, Article 10208. https://doi.org/10.1016/j.apmt.2024.102084
Tannich, F., Hamlaoui, S., & Souilem, O. (2020). The effect of sub-anesthetic doses of ketamine on plasma oxidative stress in pilocarpine-induced epilepsy in mice. Issues in Biological Sciences and Pharmaceutical Research, 7(5),106-116. https://doi.org/10.15739/ibspr.19.013
Taylor, D. D., & Shah, S. (2015). Methods of isolating extracellular vesicles impact down-stream analyses of their cargoes. Methods, 87, 3-10. https://doi.org/10.1016/j.ymeth.2015.02.019
Thompson, W., & Papoutsakis, E. T. (2023). The role of biomechanical stress in extracellular vesicle formation, composition and activity. Biotechnology Advances, 66, Article 108158. https://doi.org/10.1016/j.biotechadv.2023.108158
Uldry, A. C., Maciel-Dominguez, A., Jornod, M., Buchs, N., Braga-Lagache, S., Brodard, J., Jankovic, J., Bonadies, N., & Heller, M. (2022). Effect of sample transportation on the proteome of human circulating blood extracellular vesicles. International Journal of Molecular Sciences, 23(9), Article 4515. https://doi.org/10.3390/ijms23094515
Van Deun, J., Mestdagh, P., Sormunen, R., Cocquyt, V., Vermaelen, K., Vandesompele, J., Bracke, M., De Wever, O., & Hendrix, A. (2014). The impact of disparate isolation methods for extracellular vesicles on downstream RNA profiling. Journal of Extracellular Vesicles, 3(1), Article 24858. https://doi.org/10.3402/jev.v3.24858
van Meteren, N., Lagadic-Gossmann, D., Chevanne, M., Gallais, I., Gobart, D., Burel, A., Bucher, S., Grova, N., Fromenty, B., Appenzeller, B. M. R., Chevance, S., Gauffre, F., Le Ferrec, E., & Sergent, O. (2019). Polycyclic aromatic hydrocarbons can trigger hepatocyte release of extracellular vesicles by various mechanisms of action depending on their affinity for the aryl hydrocarbon receptor. Toxicological Sciences, 171(2), 443-462. https://doi.org/10.1093/toxsci/kfz157
Veerman, R. E., Teeuwen, L., Czarnewski, P., Güclüler Akpinar, G., Sandberg, A., Cao, X., Pernemalm, M., Orre, L. M., Gabrielsson, S., & Eldh, M. (2021). Molecular evaluation of five different isolation methods for extracellular vesicles reveals different clinical applicability and subcellular origin. Journal of Extracellular Vesicles, 10(9), Article e12128. https://doi.org/10.1002/jev2.12128
Vergauwen, G., Dhondt, B., Van Deun, J., De Smedt, E., Berx, G., Timmerman, E., Gevaert, K., Miinalainen, I., Cocquyt, V., Braems, G., Van den Broecke, R., Denys, H., De Wever, O., & Hendrix, A. (2017). Confounding factors of ultrafiltration and protein analysis in extracellular vesicle research. Scientific Reports, 7(1), Article 2704. https://doi.org/10.1038/s41598-017-02599-y
Vinken, M. (2015). Introduction: connexins, pannexins and their channels as gatekeepers of organ physiology. Cellular and Molecular Life Sciences, 72(15), 2775-2778. https://doi.org/10.1007/s00018-015-1958-3
Walbrecq, G., Margue, C., Behrmann, I., & Kreis, S. (2020). Distinct cargos of small extracellular vesicles derived from hypoxic cells and their effect on cancer cells. International Journal of Molecular Sciences, 21(14), Article 5071. https://doi.org/10.3390/ijms21145071
Wallis, R., Mizen, H., & Bishop, C. L. (2020). The bright and dark side of extracellular vesicles in the senescence-associated secretory phenotype. Mechanisms of Ageing and Development, 189, Article 111263. https://doi.org/10.1016/j.mad.2020.111263
Wang, K., Wei, Y., Liu, W., Liu, L., Guo, Z., Fan, C., Wang, L., Hu, J., & Li, B. (2019). Mechanical stress-dependent autophagy component release via extracellular nanovesicles in tumor cells. ACS Nano, 13(4), 4589-4602. https://doi.org/10.1021/acsnano.9b00587
Wang, Z., Zhou, X., Kong, Q., He, H., Sun, J., Qiu, W., Zhang, L., & Yang, M. (2024). Extracellular vesicle preparation and analysis: A state-of-the-art review. Advanced Science, 11(30), Article e2401069. https://doi.org/10.1002/advs.202401069
Weng, Z., Zhang, B., Wu, C., Yu, F., Han, B., Li, B., & Li, L. (2021). Therapeutic roles of mesenchymal stem cell-derived extracellular vesicles in cancer. Journal of Hematology and Oncology, 14(1), Article 136. https://doi.org/10.1186/s13045-021-01141-y
Wijesinghe, S. N., Anderson, J., Brown, T. J., Nanus, D. E., Housmans, B., Green, J. A., Hackl, M., Choi, K. K., Arkill, K. P., Welting, T., James, V., Jones, S. W., & Peffers, M. J. (2022). The role of extracellular vesicle miRNAs and tRNAs in synovial fibroblast senescence. Frontiers in molecular biosciences, 9, Article 971621. https://doi.org/10.3389/fmolb.2022.971621
Wilkening, A., Rüb, C., Sylvester, M., & Voos, W. (2018). Analysis of heat-induced protein aggregation in human mitochondria. The Journal of biological chemistry, 293(29), 11537-11552. https://doi.org/10.1074/jbc.RA118.002122
Wiklander, O. P. B., Brennan, M. Á., Lötvall, J., Breakefield, X. O., & El Andaloussi, S. (2019). Advances in therapeutic applications of extracellular vesicles. Science Translational Medicine, 11(492), Article eaav8521. https://doi.org/10.1126/scitranslmed.aav8521
Wu, Q., Zhang, H., Sun, S., Wang, L. & Sun, S. (2021). Extracellular vesicles and immunogenic stress in cancer. Cell Death and Disease, 12(10), Article 894. https://doi.org/10.1038/s41419-021-04171-z
Wu, X., Cao, X., Lintelmann, J., Peters, A., Koenig, W., Zimmermann, R., Schneider, A., Wolf, K., & KORA-Study group (2022a). Assessment of the association of exposure to polycyclic aromatic hydrocarbons, oxidative stress, and inflammation: A cross-sectional study in Augsburg, Germany. International Journal of Hygiene and Environmental Health, 244, Article 113993. https://doi.org/10.1016/j.ijheh.2022.113993
Wu, Y., Wang, Y., Lu, Y., Luo, X., Huang, Y., Xie, T., Pilarsky, C., Dang, Y., & Zhang, J. (2022b). Microfluidic technology for the isolation and analysis of exosomes. Micromachines, 13(10), Article 1571. https://doi.org/10.3390/mi13101571
Xi, X. J., Zeng, J. J., Lu, Y., Chen, S. H., Jiang, Z. W., He, P. J., & Mi, H. (2020). Extracellular vesicles enhance oxidative stress through P38/NF-kB pathway in ketamine-induced ulcerative cystitis. Journal of Cellular and Molecular Medicine, 24(13), 7609-7624. https://doi.org/10.1111/jcmm.15397
Yoo, T. J., Du, X., & Zhou, B. (2015). The paracrine effect of mesenchymal human stem cells restored hearing in β-tubulin induced autoimmune sensorineural hearing loss. Hearing Research, 330(Pt A), 57-61. https://doi.org/10.1016/j.heares.2015.07.021
Yuan, F., Li, Y. M., & Wang, Z. (2021). Preserving extracellular vesicles for biomedical applications: consideration of storage stability before and after isolation. Drug Delivery, 28(1), 1501-1509. https://doi.org/10.1080/10717544.2021.1951896
Yuan, Q.-L., Zhang, Y.-G., & Chen, Q. (2020). Mesenchymal stem cell (MSC)-derived extracellular vesicles: Potential therapeutics as MSC trophic mediators in regenerative medicine. The Anatomical Record, 303(6), 1735-1742. https://doi.org/10.1002/ar.24186
Zaborowski, M. P., Balaj, L., Breakefield, X. O., & Lai, C. P. (2015). Extracellular vesicles: Composition, biological relevance, and methods of study. Bioscience, 65(8), 783-797. https://doi.org/10.1093/biosci/biv084.
Zeng, Y., Qiu, Y., Jiang, W., Shen, J., Yao, X., He, X., Li, L., Fu, B., & Liu, X. (2022). Biological Features of Extracellular Vesicles and Challenges. Frontiers in Cell and Developmental Biology, 10, Article 816698. https://doi.org/10.3389/fcell.2022.816698
Zhang, H., Han, Y., Qiu, X., Wang, Y., Li, W., Liu, J., Chen, X., Li, R., Xu, F., Chen, W., Yang, Q., Fang, Y., Fan, Y., Wang, J., Zhang, H., & Zhu, T. (2020a). Association of internal exposure to polycyclic aromatic hydrocarbons with inflammation and oxidative stress in prediabetic and healthy individuals. Chemosphere, 253, Article 126748. https://doi.org/10.1016/j.chemosphere.2020.126748
Zhang, Y., Bi, J., Huang, J., Tang, Y., Du, S., & Li, P. (2020b). Exosome: A review of its classification, isolation techniques, storage, diagnostic and targeted therapy applications. International Journal of Nanomedicine, 15, 6917-6934. https://doi.org/10.2147/IJN.S264498
Zhao, A. G., Shah, K., Cromer, B., & Sumer, H. (2020). Mesenchymal stem cell-derived extracellular vesicles and their therapeutic potential. Stem Cells International, 2020, Article 8825771. https://doi.org/10.1155/2020/8825771
Zhong, H., & Yin, H. (2015). Role of lipid peroxidation derived 4-hydroxynonenal (4-HNE) in cancer: focusing on mitochondria. Redox Biology, 4, 193-199. https://doi.org/10.1016/j.redox.2014.12.011