{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T22:40:48Z","timestamp":1792449648723,"version":"4.5.0"},"reference-count":106,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:00:00Z","timestamp":1761004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Mesenchymal stem cells (MSCs), particularly their secreted exosomes, small microvesicles, represent a major focus in regenerative medicine due to their therapeutic potential. Exosomes exhibit growth factors and cytokines and are loaded with microRNAs (miRNA) and short interfering RNA (siRNA) that can be transferred to other cells, potentially affecting their function. Exosomes are crucial mediators of intercellular communication, are immunomodulatory, and are promoters of tissue regeneration. Despite their promise, the standardized methods for exosome isolation and characterization remain weak. This exploratory study addresses this gap by detailing an effective method for isolating exosomes from adipose tissue mesenchymal stem cells (AT-MSCs), emphasizing precipitation as a technique yielding a high efficiency and purity compared to other methods. Functionally, we aimed to confirm the AT-MSC exosomes\u2019 ability to exert an effective protective activity on the skin and its main components, such as fibroblasts, collagen, and elastin. To achieve this goal, we had to demonstrate that AT-MSC exosomes are safe and free of toxic substances. They can express specific proteins such as CD9, CD63, and CD81, which are well-known exosome markers. These exosomes also contain key miRNAs, including miRNA-203 A, miRNA-203 B, and miRNA-3196, important for skin regeneration, as well as enhancers of cell integrity and proliferation. We eventually confirmed the ability of exosomes to exert protective and recovery effects on fibroblasts after H2O2-induced damage in vitro, as well as on mouse skin after UVB-induced damage in vivo. These effects were verified by measuring levels of reactive oxidative species (ROS), assessing SA-\u03b2-Galactosidase (SA-\u03b2-Gal) activity, analyzing the cell cycle, evaluating the telomere length of fibroblasts by RT-PCR, and conducting histological assessments of collagen and elastin structure in murine skin after UVB exposure. This exploratory work provides valuable insights into the isolation, characterization, and bioactive and reparative properties of exosomes from AT-MSCs, supporting their development for future studies and therapeutic applications.<\/jats:p>","DOI":"10.3390\/bioengineering12101129","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T14:17:35Z","timestamp":1761056255000},"page":"1129","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Exosomes from Adipose Tissue Mesenchymal Stem Cells, a Preliminary Study for In Vitro and In Vivo Application"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5397-8000","authenticated-orcid":false,"given":"Thao Duy","family":"Huynh","sequence":"first","affiliation":[{"name":"Biomedical Research Center, Pham Ngoc Thac University of Medicine, Ho Chi Minh City 700000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciro","family":"Gargiulo Isacco","sequence":"additional","affiliation":[{"name":"Interdisciplinary Department of Medicine, Section of Microbiology and Virology, School of Medicine, The University of Bari, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan Thai Minh","family":"Ngo","sequence":"additional","affiliation":[{"name":"Biomedical Research Center, Pham Ngoc Thac University of Medicine, Ho Chi Minh City 700000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binh Thanh","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Biomedical Research Center, Pham Ngoc Thac University of Medicine, Ho Chi Minh City 700000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0635-7979","authenticated-orcid":false,"given":"Tuan Ngoc","family":"Huu 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Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1672-3292","authenticated-orcid":false,"given":"Van Hung","family":"Pham","sequence":"additional","affiliation":[{"name":"Viet Nam Research and Development Institute of Clinical Microbiology, Ho Chi Minh City 756000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5671-8124","authenticated-orcid":false,"given":"Luigi","family":"Santacroce","sequence":"additional","affiliation":[{"name":"Interdisciplinary Department of Medicine, Section of Microbiology and Virology, School of Medicine, The University of Bari, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5722-8581","authenticated-orcid":false,"given":"Toai Cong","family":"Tran","sequence":"additional","affiliation":[{"name":"Biomedical Research Center, Pham Ngoc Thac University of Medicine, Ho Chi Minh City 700000, 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(2023). Adipose Tissue-Derived Mesenchymal Stem Cell-Derived Exosomes Promote Wound Healing and Tissue Regeneration. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241310434"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1080\/14653240600855905","article-title":"Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement","volume":"8","author":"Dominici","year":"2006","journal-title":"Cytotherapy"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Kuca-Warnawin, E., Kurowska, W., Pleba\u0144czyk, M., Wajda, A., Kornatka, A., Burakowski, T., Janicka, I., Syrowka, P., and Skalska, U. (2023). Basic Properties of Adipose-Derived Mesenchymal Stem Cells of Rheumatoid Arthritis and Osteoarthritis Patients. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15031003"},{"key":"ref_4","first-page":"108","article-title":"Isolation and Characterization of Adipose-Derived Mesenchymal Stem Cell Exosomes: An In-Vitro Study","volume":"16","author":"Fiolin","year":"2022","journal-title":"J. Profesi Med. J. Kedokt. Dan Kesehat."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.jcyt.2015.11.008","article-title":"International Society for Cellular Therapy perspective on immune functional assays for mesenchymal stromal cells as potency release criterion for advanced phase clinical trials","volume":"18","author":"Galipeau","year":"2016","journal-title":"Cytotherapy"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Zaripova, L.N., Midgley, A., Christmas, S.E., Beresford, M.W., Pain, C., Baildam, E.M., and Oldershaw, R.A. (2023). Mesenchymal Stem Cells in the Pathogenesis and Therapy of Autoimmune and Autoinflammatory Diseases. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242216040"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1186\/s13287-024-03752-x","article-title":"Multipotent\/pluripotent stem cell populations in stromal tissues and peripheral blood: Exploring diversity, potential, and therapeutic applications","volume":"15","author":"Aprile","year":"2024","journal-title":"Stem Cell Res. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Alfaqeh, H.H., Idrus, R.B.H., Saim, A.B., and Nordin, A. (2025). Synergistic Effects of Natural Products and Mesenchymal Stem Cells in Osteoarthritis Treatment: A Narrative Review. Curr. Issues Mol. Biol., 47.","DOI":"10.3390\/cimb47060445"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Liu, Q., Li, S., Dupuy, A., Mai, H.L., Sailliet, N., Log\u00e9, C., Robert, J.-M.H., and Brouard, S. (2021). Exosomes as New Biomarkers and Drug Delivery Tools for the Prevention and Treatment of Various Diseases: Current Perspectives. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22157763"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Suh, J.H., Joo, H.S., Hong, E.B., Lee, H.J., and Lee, J.M. (2021). Therapeutic Application of Exosomes in Inflammatory Diseases. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22031144"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Yan, B., Lv, S., Tong, P., Yan, L., Chen, Z., Zhou, L., Yuan, Q., Guo, L., and Shan, L. (2022). Intra-Articular Injection of Adipose-Derived Stem Cells Ameliorates Pain and Cartilage Anabolism\/Catabolism in Osteoarthritis: Preclinical and Clinical Evidences. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.854025"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Storti, G., Foti, R., Foti, R., Palmesano, M., Patacchiola, M., Incognito, D., Cervelli, G., Longo, B., Scioli, M.G., and Fiorelli, E. (2025). A Comprehensive Exploration of the Biological Effects of Adipose-Derived Stem Cells in the Treatment of Systemic Sclerosis. Cells, 14.","DOI":"10.3390\/cells14060458"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"30","DOI":"10.4252\/wjsc.v13.i1.30","article-title":"Adipose-Derived Stem Cells: Pathophysiologic Implications vs Therapeutic Potential in Systemic Sclerosis","volume":"13","author":"Rosa","year":"2021","journal-title":"World J. Stem Cells"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Rozier, P., Maumus, M., Bony, C., Maria, A.T.J., Sabatier, F., Jorgensen, C., Guilpain, P., and No\u00ebl, D. (2021). Extracellular Vesicles Are More Potent than Adipose Mesenchymal Stromal Cells to Exert an Anti-Fibrotic Effect in an In Vitro Model of Systemic Sclerosis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22136837"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Zayed, M.A., Sultan, S., Alsaab, H.O., Yousof, S.M., Alrefaei, G.I., Alsubhi, N.H., Alkarim, S., Al Ghamdi, K.S., Bagabir, S.A., and Jana, A. (2022). Stem-Cell-Based Therapy: The Celestial Weapon against Neurological Disorders. Cells, 11.","DOI":"10.3390\/cells11213476"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Lau, C.S., Park, S.Y., Ethiraj, L.P., Singh, P., Raj, G., Quek, J., Prasadh, S., Choo, Y., and Goh, B.T. (2024). Role of Adipose-Derived Mesenchymal Stem Cells in Bone Regeneration. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25126805"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s13287-016-0383-3","article-title":"Potency testing of mesenchymal stromal cell growth expanded in human platelet lysate from different human tissues","volume":"7","author":"Fazzina","year":"2016","journal-title":"Stem Cell Res. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1089\/biores.2014.0059","article-title":"Subcutaneous Adipose Tissue-Derived Stem Cell Utility Is Independent of Anatomical Harvest Site","volume":"4","author":"Choudhery","year":"2015","journal-title":"BioResearch Open Access"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.cell.2013.05.039","article-title":"The hallmarks of aging","volume":"153","author":"Blasco","year":"2013","journal-title":"Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1021\/acschemneuro.3c00531","article-title":"Aging Hallmarks and Progression and Age-Related Diseases: A Landscape View of Research Advancement","volume":"15","author":"Tenchov","year":"2024","journal-title":"ACS Chem. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/s41514-024-00148-2","article-title":"Healthcare on the brink: Navigating the challenges of an aging society in the United States","volume":"10","author":"Jones","year":"2024","journal-title":"npj Aging"},{"key":"ref_22","first-page":"2554","article-title":"Targeting Cellular Senescence in Aging and Age-Related Diseases: Challenges, Considerations, and the Emerging Role of Senolytic and Senomorphic Therapies","volume":"15","author":"Zheng","year":"2024","journal-title":"Aging Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"13803","DOI":"10.18632\/aging.103504","article-title":"Physical activity, a modulator of aging through effects on telomere biology","volume":"12","author":"Semeraro","year":"2020","journal-title":"Aging"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Zuo, L., Prather, E.R., Stetskiv, M., Garrison, D.E., Meade, J.R., Peace, T.I., and Zhou, T. (2019). Inflammaging and Oxidative Stress in Human Diseases: From Molecular Mechanisms to Novel Treatments. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20184472"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s40520-013-0021-1","article-title":"Telomere, aging and age-related diseases","volume":"25","author":"Xi","year":"2013","journal-title":"Aging Clin. Exp. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1007\/s10238-025-01608-z","article-title":"The relationship between telomere length and aging-related diseases","volume":"25","author":"Huang","year":"2025","journal-title":"Clin. Exp. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"352","DOI":"10.4172\/2157-7633.1000352","article-title":"Autologous Peripheral Blood Stem Cells Increase the Telomere Length in Patient: A Case Report of 13 Patients","volume":"6","author":"Gargiulo","year":"2016","journal-title":"J. Stem Cell Res. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1016\/0014-4827(65)90211-9","article-title":"The limited in vitro lifetime of human diploid cell strains","volume":"37","author":"Hayflick","year":"1965","journal-title":"Exp. Cell Res."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Tucker, L.A., and Bates, C.J. (2024). Telomere Length and Biological Aging: The Role of Strength Training in 4814 US Men and Women. Biology, 13.","DOI":"10.3390\/biology13110883"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1007\/s12015-022-10370-8","article-title":"Telomeres and Mitochondrial Metabolism: Implications for Cellular Senescence and Age-related Diseases","volume":"18","author":"Gao","year":"2022","journal-title":"Stem Cell Rev. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s41232-024-00342-5","article-title":"Role of cellular senescence in inflammation and regeneration","volume":"44","author":"Saito","year":"2024","journal-title":"Inflamm. Regen."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Li, C., Yuan, Y., Jia, Y., Zhou, Q., Wang, Q., and Jiang, X. (2025). Cellular senescence: From homeostasis to pathological implications and therapeutic strategies. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1534263"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Kobayashi, H., Umetani, M., Nishio, M., Shigetomi, H., Imanaka, S., and Hashimoto, H. (2025). Molecular Mechanisms of Cellular Senescence in Age-Related Endometrial Dysfunction. Cells, 14.","DOI":"10.3390\/cells14120858"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Walker, B.R., and Moraes, C.T. (2022). Nuclear-Mitochondrial Interactions. Biomolecules, 12.","DOI":"10.3390\/biom12030427"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Palamarchuk, A.I., Kovalenko, E.I., and Streltsova, M.A. (2023). Multiple Actions of Telomerase Reverse Transcriptase in Cell Death Regulation. Biomedicines, 11.","DOI":"10.3390\/biomedicines11041091"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Assalve, G., Lunetti, P., Rocca, M.S., Cosci, I., Di Nisio, A., Ferlin, A., Zara, V., and Ferramosca, A. (2025). Exploring the Link Between Telomeres and Mitochondria: Mechanisms and Implications in Different Cell Types. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26030993"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Lee, Y.H., Park, J.Y., Lee, H., Song, E.S., Kuk, M.U., Joo, J., Oh, S., Kwon, H.W., Park, J.T., and Park, S.C. (2021). Targeting Mitochondrial Metabolism as a Strategy to Treat Senescence. Cells, 10.","DOI":"10.3390\/cells10113003"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Stabenow, L.K., Zibrova, D., Ender, C., Helbing, D.L., Spengler, K., Marx, C., Wang, Z.Q., and Heller, R. (2022). Oxidative Glucose Metabolism Promotes Senescence in Vascular Endothelial Cells. Cells, 11.","DOI":"10.3390\/cells11142213"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2627","DOI":"10.1158\/0008-5472.CAN-03-0846","article-title":"The tumor suppressor p53 down-regulates glucose transporters GLUT1 and GLUT4 gene expression","volume":"64","author":"Armoni","year":"2004","journal-title":"Cancer Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3565127","DOI":"10.1155\/2016\/3565127","article-title":"ROS, cell senescence, and novel molecular mechanisms in aging and age-related diseases","volume":"2016","author":"Davalli","year":"2016","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Stojanovic, B., Jovanovic, I., Dimitrijevic Stojanovic, M., Stojanovic, B.S., Kovacevic, V., Radosavljevic, I., Jovanovic, D., Miletic Kovacevic, M., Zornic, N., and Arsic, A.A. (2025). Oxidative Stress-Driven Cellular Senescence: Mechanistic Crosstalk and Therapeutic Horizons. Antioxidants, 14.","DOI":"10.3390\/antiox14080987"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.4161\/cc.6.13.4436","article-title":"Differential regulation of microRNAs by p53 revealed by massively parallel sequencing: miR-34a is a p53 target that induces apoptosis and G1-arrest","volume":"6","author":"Tarasov","year":"2007","journal-title":"Cell Cycle"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41392-023-01347-1","article-title":"Targeting p53 pathways: Mechanisms, structures and advances in therapy","volume":"8","author":"Wang","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2725","DOI":"10.1038\/s41467-024-47008-x","article-title":"Mitochondrial H2O2 release does not directly cause damage to chromosomal DNA","volume":"15","author":"Polderman","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Lettieri-Barbato, D., Aquilano, K., Punziano, C., Minopoli, G., and Faraonio, R. (2022). MicroRNAs, Long Non-Coding RNAs, and Circular RNAs in the Redox Control of Cell Senescence. Antioxidants, 11.","DOI":"10.3390\/antiox11030480"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Cruz-Ramos, J.A., de la Mora-Jim\u00e9nez, E., Llanes-Cervantes, B.A., and Dami\u00e1n-Mej\u00eda, M.A. (2025). MicroRNAs in the mitochondria-telomere axis: New insights into cancer development and potential therapeutic targets. Genes, 16.","DOI":"10.20944\/preprints202501.2256.v1"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1225578","DOI":"10.1155\/2022\/1225578","article-title":"ROS: Basic Concepts, Sources, Cellular Signaling, and its Implications in Aging Pathways","volume":"2022","author":"Dantas","year":"2022","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Kim, H.J., Kim, B., Byun, H.J., Yu, L., Nguyen, T.M., Nguyen, T.H., Fare, P.A., Kim, E.J., Cheong, K.A., and Kim, K.S. (2021). Resolvin D1 suppresses H2O2-induced senescence in fibroblasts by inducing autophagy through the miR-1299\/ARG2\/ARL1 axis. Antioxidants, 10.","DOI":"10.3390\/antiox10121924"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Yu, X., Odenthal, M., and Fries, J.W.U. (2016). Exosomes as miRNA carriers: Formation\u2013Function\u2013Future. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17122028"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Salehi, M., Kamali, M.J., Arab, D., Safaeian, N., Ashuori, Z., Maddahi, M., Latifi, N., and Jahromi, A.M. (2024). Exosomal microRNAs in regulating cancer cell resistance to apoptosis. Biochem. Biophys. Rep., 37.","DOI":"10.1016\/j.bbrep.2024.101644"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Luo, L., An, X., Xiao, Y., Sun, X., Li, S., Wang, Y., Sun, W., and Yu, D. (2024). Mitochondria-related microRNAs and their role in cellular senescence. Front. Physiol., 14.","DOI":"10.3389\/fphys.2023.1279548"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/s41580-020-00314-w","article-title":"Cellular senescence in ageing: From mechanisms to therapeutic opportunities","volume":"22","author":"Krizhanovsky","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"29556","DOI":"10.1074\/jbc.271.47.29556","article-title":"Novel form of p21(WAF1\/CIP1\/SDI1) protein in phorbol ester-induced G2\/M arrest","volume":"271","author":"Tchou","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.4161\/cc.10.15.16776","article-title":"The meaning of p16(ink4a) expression in tumors: Functional significance, clinical associations and future developments","volume":"10","author":"Witkiewicz","year":"2011","journal-title":"Cell Cycle"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Kumar, R., and Gullapalli, R.R. (2024). High Throughput Screening Assessment of Reactive Oxygen Species (ROS) Generation using Dihydroethidium (DHE) Fluorescence Dye. J. Vis. Exp. JoVE, 203.","DOI":"10.3791\/66238"},{"key":"ref_56","first-page":"e60682","article-title":"Detection of Total Reactive Oxygen Species in Adherent Cells by 2\u2032,7\u2032-Dichlorodihydrofluorescein Diacetate Staining","volume":"160","author":"Kim","year":"2020","journal-title":"J. Vis. Exp. JoVE"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/s11010-011-0764-y","article-title":"Hoechst 33342 induced reactive oxygen species and impaired expression of cytochrome c oxidase subunit 1 leading to cell death in irradiated human cancer cells","volume":"352","author":"Athar","year":"2011","journal-title":"Mol. Cell. Biochem."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Waheed, T.O., Hahn, O., Sridharan, K., M\u00f6rke, C., Kamp, G., and Peters, K. (2022). Oxidative Stress Response in Adipose Tissue-Derived Mesenchymal Stem\/Stromal Cells. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232113435"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1039\/c0pp00234h","article-title":"Phototoxicity of Hoechst 33342 in time-lapse fluorescence microscopy","volume":"9","author":"Purschke","year":"2010","journal-title":"Photochem. Photobiol. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"13860","DOI":"10.3390\/cimb46120828","article-title":"The Dose Rate of Corpuscular Ionizing Radiation Strongly Influences the Severity of DNA Damage, Cell Cycle Progression and Cellular Senescence in Human Epidermoid Carcinoma Cells","volume":"46","author":"Soroko","year":"2024","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"4861","DOI":"10.7150\/thno.97264","article-title":"Metal-organic cage as a theranostic nanoplatform for magnetic resonance imaging guided chemodynamic therapy","volume":"14","author":"Yin","year":"2024","journal-title":"Theranostics"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e2300230","DOI":"10.1002\/adhm.202300230","article-title":"Breaking a Dogma: High\u2013Throughput Live\u2013Cell Imaging in Real\u2013Time with Hoechst 33342","volume":"12","author":"Fuchs","year":"2023","journal-title":"Adv. Healthc. Mater."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"936","DOI":"10.3109\/10715762.2010.492829","article-title":"Hoechst 33342 induces radiosensitization in malignant glioma cells via increase in mitochondrial reactive oxygen species","volume":"44","author":"Athar","year":"2010","journal-title":"Free Radic. Res."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Zhang, X., Gao, Y., Zhang, S., Wang, Y., Du, Y., Hao, S., and Ni, T. (2025). The Regulation of Cellular Senescence in Cancer. Biomolecules, 15.","DOI":"10.3390\/biom15030448"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.1007\/s00204-023-03562-9","article-title":"Reactive oxygen species, toxicity, oxidative stress, and antioxidants: Chronic diseases and aging","volume":"97","author":"Jomova","year":"2023","journal-title":"Arch. Toxicol."},{"key":"ref_66","unstructured":"(2009). Biological Evaluation of Medical Devices\u2014Part 5: Tests for In Vitro Cytotoxicity. Standard No. ISO 10993-5:2009."},{"key":"ref_67","unstructured":"(2021). Biological Evaluation of Medical Devices\u2014Part 10: Tests for Skin Sensitization. Standard No. ISO 10993-10:2021."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e18239","DOI":"10.1016\/j.heliyon.2023.e18239","article-title":"Intrinsic and environmental basis of aging: A narrative review","volume":"9","author":"Navarro","year":"2023","journal-title":"Heliyon"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s00411-007-0096-1","article-title":"UVB induced oxidative stress in human keratinocytes and protective effect of antioxidant agents","volume":"46","author":"Jin","year":"2007","journal-title":"Radiat. Environ. Biophys."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Ansary, T.M., Hossain, M.R., Kamiya, K., Komine, M., and Ohtsuki, M. (2021). Inflammatory Molecules Associated with Ultraviolet Radiation-Mediated Skin Aging. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22083974"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Nan, L., Guo, P., Hui, W., Xia, F., and Yi, C. (2025). Recent advances in dermal fibroblast senescence and skin aging: Unraveling mechanisms and pioneering therapeutic strategies. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1592596"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"111525","DOI":"10.1016\/j.mad.2021.111525","article-title":"Faces of cellular senescence in skin aging","volume":"198","author":"Ho","year":"2021","journal-title":"Mech. Aging Dev."},{"key":"ref_73","first-page":"1316","article-title":"Aging and \u201cAge-Related\u201d Diseases\u2014What Is the Relation?","volume":"16","author":"Kopp","year":"2024","journal-title":"Aging Dis."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Naharro-Rodriguez, J., Bacci, S., Hernandez-Bule, M.L., Perez-Gonzalez, A., and Fernandez-Guarino, M. (2025). Decoding Skin Aging: A Review of Mechanisms, Markers, and Modern Therapies. Cosmetics, 12.","DOI":"10.3390\/cosmetics12040144"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1186\/s13287-025-04374-7","article-title":"Extracellular vesicles in age-related diseases: Disease pathogenesis, intervention, and biomarker","volume":"16","author":"Putri","year":"2025","journal-title":"Stem Cell Res. Ther."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Lyamina, S., Baranovskii, D., Kozhevnikova, E., Ivanova, T., Kalish, S., Sadekov, T., Klabukov, I., Maev, I., and Govorun, V. (2023). Mesenchymal Stromal Cells as a Driver of Inflammaging. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24076372"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s12964-022-01017-9","article-title":"The potential use of mesenchymal stem cells-derived exosomes as microRNAs delivery systems in different diseases","volume":"21","author":"Oveili","year":"2023","journal-title":"Cell Commun. Signal."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Odehnalov\u00e1, N., \u0160andrikov\u00e1, V., Hromadka, R., Skali\u010dkov\u00e1, M., Dytrych, P., Hoskovec, D., Kej\u00edk, Z., Hajduch, J., Vellieux, F., and Va\u0161\u00e1kov\u00e1, M.K. (2025). The potential of exosomes in regenerative medicine and in the diagnosis and therapies of neurodegenerative diseases and cancer. Front. Med., 12.","DOI":"10.3389\/fmed.2025.1539714"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Yang, Y.-P., Nicol, C.J.B., and Chiang, M.-C. (2025). A Review of the Neuroprotective Properties of Exosomes Derived from Stem Cells and Exosome-Coated Nanoparticles for Treating Neurodegenerative Diseases and Stroke. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26083915"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Youssef, E., Palmer, D., Fletcher, B., and Vaughn, R. (2025). Exosomes in Precision Oncology and Beyond: From Bench to Bedside in Diagnostics and Therapeutics. Cancers, 17.","DOI":"10.20944\/preprints202501.1036.v1"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Keshtkar, S., Asvar, Z., Najafi, H., Heidari, M., Kaviani, M., Sarvestani, F.S., Tamaddon, A.M., Sadati, M.S., Hamidizadeh, N., and Azarpira, N. (2025). Exosomes as natural vectors for therapeutic delivery of bioactive compounds in skin diseases. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1485769"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Saha, P., Datta, S., Ghosh, S., Samanta, A., Ghosh, P., and Sinha, D. (2021). Bioengineering of Extracellular Vesicles: Exosome-Based Next-Generation Therapeutic Strategy in Cancer. Bioengineering, 8.","DOI":"10.3390\/bioengineering8100139"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1535750","DOI":"10.1080\/20013078.2018.1535750","article-title":"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","volume":"7","author":"Witwer","year":"2018","journal-title":"J. Extracell. Vesicles"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Gorshkov, A., Purvinsh, L., Brodskaia, A., and Vasin, A. (2022). Exosomes as Natural Nanocarriers for RNA-Based Therapy and Prophylaxis. Nanomaterials, 12.","DOI":"10.3390\/nano12030524"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"102269","DOI":"10.1101\/pdb.prot102269","article-title":"Bradford Assay for Determining Protein Concentration","volume":"2020","author":"Kielkopf","year":"2020","journal-title":"Cold Spring Harb. Protoc."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/S0968-0004(02)02110-2","article-title":"Oxidative stress shortens telomeres","volume":"27","year":"2002","journal-title":"Trends Biochem. Sci."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Purnianto, A., Mawal, C., Kulkarni, M.M., Su, H., Koukoulis, T.F., Wongsodirdjo, P., Hung, Y.H., Ayton, S., Bush, A.I., and Barnham, K.J. (2024). Small extracellular vesicles contain metals and transfer metal intercellularly. J. Extracell. Biol., 3.","DOI":"10.1002\/jex2.70012"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Tienda-V\u00e1zquez, M.A., Hanel, J.M., M\u00e1rquez-Arteaga, E.M., Salgado-\u00c1lvarez, A.P., Scheckhuber, C.Q., Alanis-G\u00f3mez, J.R., Espinoza-Silva, J.I., Ramos-Kuri, M., Hern\u00e1ndez-Rosas, F., and Melchor-Mart\u00ednez, E.M. (2023). Exosomes: A Promising Strategy for Repair, Regeneration and Treatment of Skin Disorders. Cells, 12.","DOI":"10.3390\/cells12121625"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"101395","DOI":"10.4252\/wjsc.v17.i2.101395","article-title":"Exosomal miR-203 from bone marrow stem cells targets the SOCS3\/NF-\u03baB pathway to regulate neuroinflammation in temporal lobe epilepsy","volume":"17","author":"Wang","year":"2025","journal-title":"World J. Stem Cells"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Giammona, A., Di Franco, S., Lo Dico, A., and Stassi, G. (2024). The miRNA Contribution in Adipocyte Maturation. Non-Coding RNA, 10.","DOI":"10.20944\/preprints202405.0080.v1"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Song, S., Johnson, K.S., Lujan, H., Pradhan, S.H., Sayes, C.M., and Taube, J.H. (2021). Nanoliposomal Delivery of MicroRNA-203 Suppresses Migration of Triple-Negative Breast Cancer through Distinct Target Suppression. Non-Coding RNA, 7.","DOI":"10.3390\/ncrna7030045"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Giunco, S., Petrara, M.R., Indraccolo, S., Ciminale, V., and De Rossi, A. (2025). Beyond Telomeres: Unveiling the Extratelomeric Functions of TERT in B-Cell Malignancies. Cancers, 17.","DOI":"10.3390\/cancers17071165"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Tapparo, M., Pomatto, M.A.C., Deregibus, M.C., Papadimitriou, E., Cavallari, C., D\u2019Antico, S., Collino, F., and Camussi, G. (2021). Serum Derived Extracellular Vesicles Mediated Delivery of Synthetic miRNAs in Human Endothelial Cells. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.636587"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Li, S., Liu, F., Zhang, S., Sun, X., Li, X., Yue, Q., Su, L., Yang, S., and Zhao, L. (2025). Lavender Exosome-Like nanoparticles attenuate UVB-Induced Photoaging via miR166-Mediated inflammation and collagen regulation. Sci. Rep., 15.","DOI":"10.1038\/s41598-025-08817-2"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"4598","DOI":"10.1128\/MCB.23.13.4598-4610.2003","article-title":"Hydrogen peroxide triggers nuclear export of telomerase reverse transcriptase via Src kinase family-dependent phosphorylation of tyrosine 707","volume":"23","author":"Haendeler","year":"2003","journal-title":"Mol. Cell. Biol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"486","DOI":"10.4103\/ijd.ijd_568_23","article-title":"miRNA: The Next Frontier in Dermatology Research and Therapeutics","volume":"69","author":"Sil","year":"2024","journal-title":"Indian J. Dermatol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.exger.2017.01.009","article-title":"Molecular mechanisms of UVB-induced senescence of dermal fibroblasts and its relevance for photoaging of the human skin","volume":"94","author":"Cavinato","year":"2017","journal-title":"Exp. Gerontol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"e374","DOI":"10.1002\/hsr2.374","article-title":"Targeting microRNA for improved skin health","volume":"4","author":"Li","year":"2021","journal-title":"Health Sci. Rep."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1038\/cdd.2008.69","article-title":"miR-203 represses \u2018stemness\u2019 by repressing DeltaNp63","volume":"15","author":"Lena","year":"2008","journal-title":"Cell Death Differ."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"10644","DOI":"10.1128\/JVI.00703-10","article-title":"MicroRNA 203 expression in keratinocytes is dependent on regulation of p53 levels by E6","volume":"84","author":"McKenna","year":"2010","journal-title":"J. Virol."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Zhang, S., Yang, Y., Lv, X., Zhou, X., Zhao, W., Meng, L., Zhu, S., Zhang, Z., and Wang, Y. (2024). Exosome Cargo in Neurodegenerative Diseases: Leveraging Their Intercellular Communication Capabilities for Biomarker Discovery and Therapeutic Delivery. Brain Sci., 14.","DOI":"10.3390\/brainsci14111049"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/j.jid.2021.07.167","article-title":"Role of Exosomes in Dermal Wound Healing: A Systematic Review","volume":"142","author":"Prasai","year":"2022","journal-title":"J. Investig. Dermatol."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Al Halawani, A., Mithieux, S.M., Yeo, G.C., Hosseini-Beheshti, E., and Weiss, A.S. (2022). Extracellular Vesicles: Interplay with the Extracellular Matrix and Modulated Cell Responses. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23063389"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"S193","DOI":"10.33549\/physiolres.935153","article-title":"Circulating exosomal miRNAs as a promising diagnostic biomarker in cancer","volume":"72","author":"Bugala","year":"2023","journal-title":"Physiol. Res."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Bai, L., Yu, L., Ran, M., Zhong, X., Sun, M., Xu, M., Wang, Y., Yan, X., Lee, R.J., and Tang, Y. (2025). Harnessing the Potential of Exosomes in Therapeutic Interventions for Brain Disorders. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26062491"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"102121","DOI":"10.1016\/j.tranon.2024.102121","article-title":"A comprehensive review on recent advances in exosome isolation and characterization: Toward clinical applications","volume":"50","author":"Dilsiz","year":"2024","journal-title":"Transl. 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