{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:45:32Z","timestamp":1790779532910,"version":"4.1.0"},"reference-count":59,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["NSTC 112-2314-B-038-040-MY3"],"award-info":[{"award-number":["NSTC 112-2314-B-038-040-MY3"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018493","name":"Taipei Medical University-Shuang Ho Hospital, Ministry of Health and Welfare","doi-asserted-by":"publisher","award":["112TMU-SHH-28"],"award-info":[{"award-number":["112TMU-SHH-28"]}],"id":[{"id":"10.13039\/100018493","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Stem Cell Rev and Rep"],"published-print":{"date-parts":[[2026,1]]},"DOI":"10.1007\/s12015-025-11005-4","type":"journal-article","created":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T11:34:04Z","timestamp":1760355244000},"page":"579-598","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Exosome Purification Strategy Influences the Regenerative Efficacy of Dental Pulp Stem Cell-Derived Exosomes in Bone Regeneration"],"prefix":"10.1007","volume":"22","author":[{"given":"Borae","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Yi","family":"Hung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Ting","family":"Chien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Che","family":"Hsieh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Hao","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Hui","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pin-Chuang","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng-Wei","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,13]]},"reference":[{"key":"11005_CR1","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1146\/annurev-chembioeng-061010-114257","volume":"2","author":"F Berthiaume","year":"2011","unstructured":"Berthiaume, F., Maguire, T. J., & Yarmush, M. L. (2011). Tissue engineering and regenerative medicine: History, progress, and challenges. Annual Review of Chemical and Biomolecular Engineering, 2, 403\u2013430.","journal-title":"Annual Review of Chemical and Biomolecular Engineering"},{"key":"11005_CR2","doi-asserted-by":"publisher","first-page":"120718","DOI":"10.1016\/j.biomaterials.2021.120718","volume":"272","author":"A Liu","year":"2021","unstructured":"Liu, A., Lin, D., Zhao, H., Chen, L., Cai, B., Lin, K., & Shen, S. G. (2021). Optimized BMSC-derived osteoinductive exosomes immobilized in hierarchical scaffold via lyophilization for bone repair through Bmpr2\/Acvr2b competitive receptor-activated Smad pathway. Biomaterials, 272, 120718.","journal-title":"Biomaterials"},{"key":"11005_CR3","doi-asserted-by":"publisher","first-page":"1810","DOI":"10.1007\/s12015-021-10172-4","volume":"17","author":"YH Chan","year":"2021","unstructured":"Chan, Y. H., Lee, Y. C., Hung, C. Y., Yang, P. J., Lai, P. C., & Feng, S. W. (2021). Three-dimensional spheroid culture enhances multipotent differentiation and stemness capacities of human dental pulp-derived mesenchymal stem cells by modulating MAPK and NF-\u03baB signaling pathways. Stem Cell Reviews and Reports, 17, 1810\u20131826.","journal-title":"Stem Cell Reviews and Reports"},{"key":"11005_CR4","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1186\/s13287-022-02744-z","volume":"13","author":"YH Chan","year":"2022","unstructured":"Chan, Y. H., Ho, K. N., Lee, Y. C., Chou, M. J., Lew, W. Z., Huang, H. M., Lai, P. C., & Feng, S. W. (2022). Melatonin enhances osteogenic differentiation of dental pulp mesenchymal stem cells by regulating MAPK pathways and promotes the efficiency of bone regeneration in calvarial bone defects. Stem Cell Research & Therapy, 13, 73.","journal-title":"Stem Cell Research & Therapy"},{"key":"11005_CR5","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1186\/s12951-021-01113-x","volume":"19","author":"Y Ding","year":"2021","unstructured":"Ding, Y., Li, Y., Sun, Z., Han, X., Chen, Y., Ge, Y., Mao, Z., & Wang, W. (2021). Cell-derived extracellular vesicles and membranes for tissue repair. Journal of Nanobiotechnology, 19, 368.","journal-title":"Journal of Nanobiotechnology"},{"key":"11005_CR6","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/s13045-021-01037-x","volume":"14","author":"T Zhou","year":"2021","unstructured":"Zhou, T., Yuan, Z., Weng, J., Pei, D., Du, X., He, C., & Lai, P. (2021). Challenges and advances in clinical applications of mesenchymal stromal cells. Journal of Hematology & Oncology, 14, 24.","journal-title":"Journal of Hematology & Oncology"},{"key":"11005_CR7","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1038\/s41569-020-0389-5","volume":"17","author":"RC de Abreu","year":"2020","unstructured":"de Abreu, R. C., Fernandes, H., da Costa Martins, P. A., Sahoo, S., Emanueli, C., & Ferreira, L. (2020). Native and bioengineered extracellular vesicles for cardiovascular therapeutics. Nature Reviews Cardiology, 17, 685\u2013697.","journal-title":"Nature Reviews Cardiology"},{"key":"11005_CR8","doi-asserted-by":"publisher","first-page":"1609206","DOI":"10.1080\/20013078.2019.1609206","volume":"8","author":"KW Witwer","year":"2019","unstructured":"Witwer, K. W., Van Balkom, B. W. M., Bruno, S., Choo, A., Dominici, M., Gimona, M., Hill, A. F., De Kleijn, D., Koh, M., Lai, R. C., Mitsialis, S. A., Ortiz, L. A., Rohde, E., Asada, T., Toh, W. S., Weiss, D. J., Zheng, L., Giebel, B., & Lim, S. K. (2019). Defining mesenchymal stromal cell (MSC)-derived small extracellular vesicles for therapeutic applications. Journal of Extracellular Vesicles, 8, 1609206.","journal-title":"Journal of Extracellular Vesicles"},{"key":"11005_CR9","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1007\/s12015-022-10342-y","volume":"19","author":"H Kong","year":"2023","unstructured":"Kong, H., Liu, P., Li, H., Zeng, X., Xu, P., Yao, X., Liu, S., Cheng, C. K., & Xu, J. (2023). Mesenchymal stem cell-derived extracellular vesicles: The novel therapeutic option for regenerative dentistry. Stem Cell Reviews and Reports, 19, 46\u201358.","journal-title":"Stem Cell Reviews and Reports"},{"key":"11005_CR10","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1038\/nrm.2017.125","volume":"19","author":"G van Niel","year":"2018","unstructured":"van Niel, G., D\u2019Angelo, G., & Raposo, G. (2018). Shedding light on the cell biology of extracellular vesicles. Nature Reviews Molecular Cell Biology, 19, 213\u2013228.","journal-title":"Nature Reviews Molecular Cell Biology"},{"key":"11005_CR11","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2021.04.013","volume":"175","author":"A Nagelkerke","year":"2021","unstructured":"Nagelkerke, A., Ojansivu, M., van der Koog, L., Whittaker, T. E., Cunnane, E. M., Silva, A. M., Dekker, N., & Stevens, M. M. (2021). Extracellular vesicles for tissue repair and regeneration: Evidence, challenges and opportunities. Advanced Drug Delivery Reviews, 175, Article 113775.","journal-title":"Advanced Drug Delivery Reviews"},{"key":"11005_CR12","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1007\/s13238-021-00863-6","volume":"13","author":"A Thakur","year":"2022","unstructured":"Thakur, A., Ke, X., Chen, Y. W., Motallebnejad, P., Zhang, K., Lian, Q., & Chen, H. J. (2022). The mini player with diverse functions: Extracellular vesicles in cell biology, disease, and therapeutics. Protein & Cell, 13, 631\u2013654.","journal-title":"Protein & Cell"},{"key":"11005_CR13","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1521230113","volume":"113","author":"J Kowal","year":"2016","unstructured":"Kowal, J., Arras, G., Colombo, M., Jouve, M., Morath, J. P., Primdal-Bengtson, B., Dingli, F., Loew, D., Tkach, M., & Th\u00e9ry, C. (2016). Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes. Proceedings of the National Academy of Sciences, 113, Article E968\u2013E977.","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"11005_CR14","doi-asserted-by":"publisher","DOI":"10.3390\/cells8070727","volume":"8","author":"LM Doyle","year":"2019","unstructured":"Doyle, L. M., & Wang, M. Z. (2019). Overview of extracellular vesicles, their origin, composition, purpose, and methods for exosome isolation and analysis. Cells, 8, Article 727.","journal-title":"Cells"},{"key":"11005_CR15","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s13578-019-0282-2","volume":"9","author":"Y Zhang","year":"2019","unstructured":"Zhang, Y., Liu, Y., Liu, H., & Tang, W. H. (2019). Exosomes: Biogenesis, biologic function and clinical potential. Cell & Bioscience, 9, 19.","journal-title":"Cell & Bioscience"},{"key":"11005_CR16","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202003505","volume":"8","author":"F Teng","year":"2020","unstructured":"Teng, F., & Fussenegger, M. (2020). Shedding light on extracellular vesicle biogenesis and bioengineering. Advanced Science, 8, Article 2003505.","journal-title":"Advanced Science"},{"key":"11005_CR17","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1038\/s41419-022-05034-x","volume":"13","author":"M Kou","year":"2022","unstructured":"Kou, M., Huang, L., Yang, J., Chiang, Z., Chen, S., Liu, J., Guo, L., Zhang, X., Zhou, X., Xu, X., Yan, X., Wang, Y., Zhang, J., Xu, A., Tse, H. F., & Lian, Q. (2022). Mesenchymal stem cell-derived extracellular vesicles for Immunomodulation and regeneration: A next generation therapeutic tool? Cell Death & Disease, 13, 580.","journal-title":"Cell Death & Disease"},{"key":"11005_CR18","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-023-02277-4","volume":"21","author":"J Ren","year":"2023","unstructured":"Ren, J., Jing, X., Liu, Y., Liu, J., Ning, X., Zong, M., Zhang, R., Cheng, H., Cui, J., Li, B., & Wu, X. (2023). Exosome-based engineering strategies for the diagnosis and treatment of oral and maxillofacial diseases. Journal Of Nanobiotechnology, 21, Article 501.","journal-title":"Journal Of Nanobiotechnology"},{"key":"11005_CR19","doi-asserted-by":"publisher","DOI":"10.1080\/20013078.2018.1560809","volume":"8","author":"K Takov","year":"2018","unstructured":"Takov, K., Yellon, D. M., & Davidson, S. M. (2018). Comparison of small extracellular vesicles isolated from plasma by ultracentrifugation or size-exclusion chromatography: Yield, purity and functional potential. Journal of Extracellular Vesicles, 8, Article 1560809.","journal-title":"Journal of Extracellular Vesicles"},{"key":"11005_CR20","doi-asserted-by":"publisher","DOI":"10.3390\/cells11091375","volume":"11","author":"L Ginini","year":"2022","unstructured":"Ginini, L., Billan, S., Fridman, E., & Gil, Z. (2022). Insight into extracellular vesicle\u2013cell communication: From cell recognition to intracellular fate. Cells, 11, Article 1375.","journal-title":"Cells"},{"key":"11005_CR21","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau6977","volume":"367","author":"R Kalluri","year":"2020","unstructured":"Kalluri, R., & LeBleu, V. S. (2020). The biology, function, and biomedical applications of exosomes. Science, 367, Article eaau6977.","journal-title":"Science"},{"key":"11005_CR22","doi-asserted-by":"publisher","first-page":"1628","DOI":"10.1016\/j.ymthe.2020.04.020","volume":"28","author":"H Kim","year":"2020","unstructured":"Kim, H., Lee, M. J., Bae, E. H., Ryu, J. S., Kaur, G., Kim, H. J., Kim, J. Y., Barreda, H., Jung, S. Y., Choi, J. M., Shigemoto-Kuroda, T., Oh, J. Y., & Lee, R. H. (2020). Comprehensive molecular profiles of functionally effective MSC-derived extracellular vesicles in immunomodulation. Molecular Therapy, 28, 1628\u20131644.","journal-title":"Molecular Therapy"},{"key":"11005_CR23","doi-asserted-by":"crossref","unstructured":"Lee, A. E., Choi, J. G., Shi, S. H., He, P., Zhang, Q. Z., & Le, A. D. (2022). DPSC-derived extracellular vesicles promote rat jawbone regeneration. Journal of Dental Research, 220345221133716.","DOI":"10.1177\/00220345221133716"},{"key":"11005_CR24","doi-asserted-by":"publisher","first-page":"e12044","DOI":"10.1002\/jev2.12044","volume":"10","author":"L Dong","year":"2020","unstructured":"Dong, L., Zieren, R. C., Horie, K., Kim, C. J., Mallick, E., Jing, Y., Feng, M., Kuczler, M. D., Green, J., Amend, S. R., Witwer, K. W., de Reijke, T. M., Cho, Y. K., Pienta, K. J., & Xue, W. (2020). Comprehensive evaluation of methods for small extracellular vesicles separation from human plasma, urine and cell culture medium. Journal of Extracellular Vesicles, 10, e12044.","journal-title":"Journal of Extracellular Vesicles"},{"key":"11005_CR25","doi-asserted-by":"publisher","DOI":"10.1177\/20417314211008626","volume":"12","author":"JY Kim","year":"2021","unstructured":"Kim, J. Y., Rhim, W. K., Yoo, Y. I., Kim, D. S., Ko, K. W., Heo, Y., Park, C. G., & Han, D. K. (2021). Defined MSC exosome with high yield and purity to improve regenerative activity. Journal of Tissue Engineering, 12, Article 20417314211008626.","journal-title":"Journal of Tissue Engineering"},{"key":"11005_CR26","doi-asserted-by":"publisher","first-page":"e12128","DOI":"10.1002\/jev2.12128","volume":"10","author":"RE Veerman","year":"2021","unstructured":"Veerman, R. E., Teeuwen, L., Czarnewski, P., G\u00fccl\u00fcler 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, e12128.","journal-title":"Journal of Extracellular Vesicles"},{"key":"11005_CR27","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2021.811971","volume":"9","author":"J Chen","year":"2022","unstructured":"Chen, J., Li, P., Zhang, T., Xu, Z., Huang, X., Wang, R., & Du, L. (2022). Review on strategies and technologies for exosome isolation and purification. Frontiers in Bioengineering and Biotechnology, 9, Article 811971.","journal-title":"Frontiers in Bioengineering and Biotechnology"},{"key":"11005_CR28","doi-asserted-by":"publisher","first-page":"7123","DOI":"10.1007\/s00216-022-04253-7","volume":"414","author":"WZ Liu","year":"2022","unstructured":"Liu, W. Z., Ma, Z. J., & Kang, X. W. (2022). Current status and outlook of advances in exosome isolation. Analytical and Bioanalytical Chemistry, 414, 7123\u20137141.","journal-title":"Analytical and Bioanalytical Chemistry"},{"key":"11005_CR29","doi-asserted-by":"crossref","unstructured":"Balbi, C., Parisse, P., Vondracek, H., Lazzarini, E., Bolis, S., Fertig, T. E., Gherghiceanu, M., Barile, L., & Vassalli, G. (2023). Impact of isolation methods on extracellular vesicle functionality in vitro and in vivo. Advanced Biology, e2300185.","DOI":"10.1002\/adbi.202300185"},{"key":"11005_CR30","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.jcyt.2023.11.001","volume":"26","author":"R Malvicini","year":"2024","unstructured":"Malvicini, R., De Lazzari, G., Tolomeo, A. M., Santa-Cruz, D., Ullah, M., Cirillo, C., Grumati, P., Pacienza, N., Muraca, M., & Yannarelli, G. (2024). Influence of the isolation method on characteristics and functional activity of mesenchymal stromal cell-derived extracellular vesicles. Cytotherapy, 26, 157\u2013170.","journal-title":"Cytotherapy"},{"key":"11005_CR31","doi-asserted-by":"publisher","DOI":"10.1177\/20417314231155114","volume":"14","author":"S Williams","year":"2023","unstructured":"Williams, S., Jalal, A. R., Lewis, M. P., & Davies, O. G. (2023). A survey to evaluate parameters governing the selection and application of extracellular vesicle isolation methods. Journal of Tissue Engineering, 14, Article 20417314231155114.","journal-title":"Journal of Tissue Engineering"},{"key":"11005_CR32","doi-asserted-by":"publisher","first-page":"e110","DOI":"10.1002\/cpcb.110","volume":"88","author":"C Coughlan","year":"2020","unstructured":"Coughlan, C., Bruce, K. D., Burgy, O., Boyd, C., et al. (2020). Exosome isolation by ultracentrifugation and precipitation and techniques for downstream analyses. Current Protocols in Cell Biology, 88, e110.","journal-title":"Current Protocols in Cell Biology"},{"key":"11005_CR33","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202002596","volume":"7","author":"BF Hettich","year":"2020","unstructured":"Hettich, B. F., Ben-Yehuda Greenwald, M., Werner, S., & Leroux, J. C. (2020). Exosomes for wound healing: Purification optimization and identification of bioactive components. Advanced Science, 7, Article 2002596.","journal-title":"Advanced Science"},{"key":"11005_CR34","doi-asserted-by":"publisher","first-page":"e12266","DOI":"10.1002\/jev2.12266","volume":"11","author":"KS Visan","year":"2022","unstructured":"Visan, K. S., Lobb, R. J., Ham, S., Lima, L. G., Palma, C., Edna, C. P. Z., Wu, L. Y., Gowda, H., Datta, K. K., Hartel, G., Salomon, C., & M\u00f6ller, A. (2022). Comparative analysis of tangential flow filtration and ultracentrifugation, both combined with subsequent size exclusion chromatography, for the isolation of small extracellular vesicles. Journal of Extracellular Vesicles, 11, e12266.","journal-title":"Journal of Extracellular Vesicles"},{"key":"11005_CR35","doi-asserted-by":"publisher","first-page":"2369","DOI":"10.1007\/s00018-019-03071-y","volume":"76","author":"M Mongui\u00f3-Tortajada","year":"2019","unstructured":"Mongui\u00f3-Tortajada, M., G\u00e1lvez-Mont\u00f3n, C., Bayes-Genis, A., Roura, S., & Borr\u00e0s, F. E. (2019). Extracellular vesicle isolation methods: Rising impact of size-exclusion chromatography. Cellular And Molecular Life Sciences, 76, 2369\u20132382.","journal-title":"Cellular And Molecular Life Sciences"},{"key":"11005_CR36","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12358","volume":"12","author":"Z Zhang","year":"2023","unstructured":"Zhang, Z., Yu, K., You, Y., Jiang, P., Wu, Z., DeTure, M. A., Dickson, D. W., Ikezu, S., Peng, J., & Ikezu, T. (2023). Comprehensive characterization of human brain-derived extracellular vesicles using multiple isolation methods: Implications for diagnostic and therapeutic applications. Journal of Extracellular Vesicles, 12, Article e12358.","journal-title":"Journal of Extracellular Vesicles"},{"key":"11005_CR37","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1186\/s13287-022-02767-6","volume":"13","author":"L Ma","year":"2022","unstructured":"Ma, L., Rao, N., Jiang, H., Dai, Y., Yang, S., Yang, H., & Hu, J. (2022). Small extracellular vesicles from dental follicle stem cells provide biochemical cues for periodontal tissue regeneration. Stem Cell Research & Therapy, 13, 92.","journal-title":"Stem Cell Research & Therapy"},{"key":"11005_CR38","doi-asserted-by":"publisher","DOI":"10.1186\/s41232-021-00163-w","volume":"41","author":"Y Imanishi","year":"2021","unstructured":"Imanishi, Y., Hata, M., Matsukawa, R., Aoyagi, A., Omi, M., Mizutani, M., Naruse, K., Ozawa, S., Honda, M., Matsubara, T., & Takebe, J. (2021). Efficacy of extracellular vesicles from dental pulp stem cells for bone regeneration in rat calvarial bone defects. Inflammation and Regeneration, 41, Article 12.","journal-title":"Inflammation and Regeneration"},{"key":"11005_CR39","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1016\/j.tibtech.2023.01.003","volume":"41","author":"PM Pincela Lins","year":"2023","unstructured":"Pincela Lins, P. M., Pirlet, E., Szymonik, M., Bronckaers, A., & Nelissen, I. (2023). Manufacture of extracellular vesicles derived from mesenchymal stromal cells. Trends in Biotechnology, 41, 965\u2013981.","journal-title":"Trends in Biotechnology"},{"key":"11005_CR40","doi-asserted-by":"publisher","first-page":"3684","DOI":"10.7150\/thno.41580","volume":"10","author":"D Yang","year":"2020","unstructured":"Yang, D., Zhang, W., Zhang, H., Zhang, F., Chen, L., Ma, L., Larcher, L. M., Chen, S., Liu, N., Zhao, Q., Tran, P. H. L., Chen, C., Veedu, R. N., & Wang, T. (2020). Progress, opportunity, and perspective on exosome isolation \u2013 Efforts for efficient exosome-based theranostics. Theranostics, 10, 3684\u20133707.","journal-title":"Theranostics"},{"key":"11005_CR41","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.70725","volume":"10","author":"D Ter-Ovanesyan","year":"2021","unstructured":"Ter-Ovanesyan, D., Norman, M., Lazarovits, R., Trieu, W., Lee, J. H., Church, G. M., & Walt, D. R. (2021). Framework for rapid comparison of extracellular vesicle isolation methods. eLife, 10, Article e70725.","journal-title":"eLife"},{"key":"11005_CR42","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20194684","volume":"20","author":"N Ludwig","year":"2019","unstructured":"Ludwig, N., Whiteside, T. L., & Reichert, T. E. (2019). Challenges in exosome isolation and analysis in health and disease. International Journal of Molecular Sciences, 20, Article 4684.","journal-title":"International Journal of Molecular Sciences"},{"key":"11005_CR43","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1038\/s41565-021-00931-2","volume":"16","author":"IK Herrmann","year":"2021","unstructured":"Herrmann, I. K., Wood, M. J. A., & Fuhrmann, G. (2021). Extracellular vesicles as a next-generation drug delivery platform. Nature Nanotechnology, 16, 748\u2013759.","journal-title":"Nature Nanotechnology"},{"key":"11005_CR44","doi-asserted-by":"publisher","first-page":"910","DOI":"10.1002\/sctm.20-0376","volume":"10","author":"RMS Cardoso","year":"2021","unstructured":"Cardoso, R. M. S., Rodrigues, S. C., Gomes, C. F., Duarte, F. V., Romao, M., Leal, E. C., Freire, P. C., Neves, R., & Sim\u00f5es-Correia, J. (2021). Development of an optimized and scalable method for isolation of umbilical cord blood-derived small extracellular vesicles for future clinical use. Stem Cells Translational Medicine, 10, 910\u2013921.","journal-title":"Stem Cells Translational Medicine"},{"key":"11005_CR45","doi-asserted-by":"publisher","DOI":"10.1080\/20013078.2019.1692401","volume":"9","author":"S Shu","year":"2019","unstructured":"Shu, S., Yang, Y., Allen, C. L., Hurley, E., Tung, K. H., Minderman, H., Wu, Y., & Ernstoff, M. S. (2019). Purity and yield of melanoma exosomes are dependent on isolation method. Journal of Extracellular Vesicles, 9, Article 1692401.","journal-title":"Journal of Extracellular Vesicles"},{"key":"11005_CR46","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12087","volume":"10","author":"JA Mart\u00ednez-Greene","year":"2021","unstructured":"Mart\u00ednez-Greene, J. A., Hern\u00e1ndez-Ortega, K., Quiroz-Baez, R., Resendis-Antonio, O., Pichardo-Casas, I., Sinclair, D. A., Budnik, B., Hidalgo-Miranda, A., Uribe-Querol, E., Ramos-God\u00ednez, M. D. P., & Mart\u00ednez-Mart\u00ednez, E. (2021). Quantitative proteomic analysis of extracellular vesicle subgroups isolated by an optimized method combining polymer-based precipitation and size exclusion chromatography. Journal of Extracellular Vesicles, 10, Article e12087.","journal-title":"Journal of Extracellular Vesicles"},{"key":"11005_CR47","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1186\/s13287-020-02032-8","volume":"11","author":"ZG Wang","year":"2020","unstructured":"Wang, Z. G., He, Z. Y., Liang, S., Yang, Q., Cheng, P., & Chen, A. M. (2020). Comprehensive proteomic analysis of exosomes derived from human bone marrow, adipose tissue, and umbilical cord mesenchymal stem cells. Stem Cell Research & Therapy, 11, 511.","journal-title":"Stem Cell Research & Therapy"},{"key":"11005_CR48","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2020.461773","volume":"1636","author":"T Liangsupree","year":"2021","unstructured":"Liangsupree, T., Multia, E., & Riekkola, M. L. (2021). Modern isolation and separation techniques for extracellular vesicles. Journal Of Chromatography A, 1636, Article 461773.","journal-title":"Journal Of Chromatography A"},{"key":"11005_CR49","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/s13287-024-03639-x","volume":"15","author":"N Al-Sharabi","year":"2024","unstructured":"Al-Sharabi, N., Mohamed-Ahmed, S., Shanbhag, S., Kampleitner, C., Elnour, R., Yamada, S., Rana, N., Birkeland, E., Tangl, S., Gruber, R., & Mustafa, K. (2024). Osteogenic human MSC-derived extracellular vesicles regulate MSC activity and osteogenic differentiation and promote bone regeneration in a rat calvarial defect model. Stem Cell Research & Therapy, 15, 33.","journal-title":"Stem Cell Research & Therapy"},{"key":"11005_CR50","doi-asserted-by":"publisher","first-page":"519","DOI":"10.2147\/IJN.S346755","volume":"17","author":"B Zhao","year":"2022","unstructured":"Zhao, B., Chen, Q., Zhao, L., Mao, J., Huang, W., Han, X., & Liu, Y. (2022). Periodontal ligament stem cell-derived small extracellular vesicles embedded in matrigel enhance bone repair through the adenosine receptor signaling pathway. International Journal of Nanomedicine, 17, 519\u2013536.","journal-title":"International Journal of Nanomedicine"},{"key":"11005_CR51","doi-asserted-by":"publisher","first-page":"e12396","DOI":"10.1002\/jev2.12396","volume":"13","author":"SI van de Wakker","year":"2024","unstructured":"van de Wakker, S. I., Bauz\u00e1-Martinez, J., R\u00edos Arceo, C., Manjikian, H., Snijders Blok, C. J. B., Roefs, M. T., Willms, E., Maas, R. G. C., Pronker, M. F., de Jong, O. G., Wu, W., G\u00f6rgens, A., Andaloussi, E., Sluijter, S., J. P. G., & Vader, P. (2024). Size matters: Functional differences of small extracellular vesicle subpopulations in cardiac repair responses. Journal of Extracellular Vesicles, 13, e12396.","journal-title":"Journal of Extracellular Vesicles"},{"key":"11005_CR52","doi-asserted-by":"publisher","first-page":"113961","DOI":"10.1016\/j.addr.2021.113961","volume":"178","author":"D Gupta","year":"2021","unstructured":"Gupta, D., Zickler, A. M., & Andaloussi, E., S (2021). Dosing extracellular vesicles. Advanced Drug Delivery Reviews, 178, 113961.","journal-title":"Advanced Drug Delivery Reviews"},{"key":"11005_CR53","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.actbio.2020.09.052","volume":"118","author":"WB Swanson","year":"2020","unstructured":"Swanson, W. B., Zhang, Z., Xiu, K., Gong, T., Eberle, M., Wang, Z., & Ma, P. X. (2020). Scaffolds with controlled release of pro-mineralization exosomes to promote craniofacial bone healing without cell transplantation. Acta Biomaterialia, 118, 215\u2013232.","journal-title":"Acta Biomaterialia"},{"key":"11005_CR54","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1016\/j.actbio.2020.04.017","volume":"109","author":"CC Huang","year":"2020","unstructured":"Huang, C. C., Kang, M., Lu, Y., Shirazi, S., Diaz, J. I., Cooper, L. F., Gajendrareddy, P., & Ravindran, S. (2020). Functionally engineered extracellular vesicles improve bone regeneration. Acta Biomaterialia, 109, 182\u2013194.","journal-title":"Acta Biomaterialia"},{"key":"11005_CR55","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1016\/j.bioactmat.2022.01.041","volume":"14","author":"Y Gao","year":"2022","unstructured":"Gao, Y., Yuan, Z., Yuan, X., Wan, Z., Yu, Y., Zhan, Q., Zhao, Y., Han, J., Huang, J., Xiong, C., & Cai, Q. (2022). Bioinspired porous microspheres for sustained hypoxic exosomes release and vascularized bone regeneration. Bioactive Materials, 14, 377\u2013388.","journal-title":"Bioactive Materials"},{"key":"11005_CR56","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbiosy.2023.100078","volume":"11","author":"J Shi","year":"2023","unstructured":"Shi, J., Teo, K. Y. W., Zhang, S., Lai, R. C., Rosa, V., Tong, H. J., Duggal, M. S., Lim, S. K., & Toh, W. S. (2023). Mesenchymal stromal cell exosomes enhance dental pulp cell functions and promote pulp\u2013dentin regeneration. Biomaterials and Biosystems, 11, Article 100078.","journal-title":"Biomaterials and Biosystems"},{"key":"11005_CR57","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.101526","volume":"298","author":"R Borza","year":"2022","unstructured":"Borza, R., Salgado-Polo, F., Moolenaar, W. H., & Perrakis, A. (2022). Structure and function of the ecto-nucleotide pyrophosphatase\/phosphodiesterase (ENPP) family: Tidying up diversity. Journal of Biological Chemistry, 298, Article 101526.","journal-title":"Journal of Biological Chemistry"},{"key":"11005_CR58","doi-asserted-by":"publisher","first-page":"C843","DOI":"10.1152\/ajpcell.00692.2023","volume":"326","author":"IL Tourkova","year":"2024","unstructured":"Tourkova, I. L., Larrouture, Q. C., Liu, S., Luo, J., Schlesinger, P. H., & Blair, H. C. (2024). The ecto-nucleotide pyrophosphatase\/phosphodiesterase 2 promotes early osteoblast differentiation and mineralization in stromal stem cells. American Journal of Physiology \u2013 Cell Physiology, 326, C843\u2013C849.","journal-title":"American Journal of Physiology \u2013 Cell Physiology"},{"key":"11005_CR59","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1016\/j.bone.2012.06.015","volume":"51","author":"BJ Kim","year":"2012","unstructured":"Kim, B. J., Lee, Y. S., Lee, S. Y., Park, S. Y., Dieplinger, H., Ryu, S. H., Yea, K., Choi, S., Lee, S. H., Koh, J. M., & Kim, G. S. (2012). Afamin secreted from nonresorbing osteoclasts acts as a chemokine for preosteoblasts via the Akt-signaling pathway. Bone, 51, 431\u2013440.","journal-title":"Bone"}],"container-title":["Stem Cell Reviews and Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12015-025-11005-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12015-025-11005-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12015-025-11005-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T22:17:25Z","timestamp":1768342645000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12015-025-11005-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,13]]},"references-count":59,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["11005"],"URL":"https:\/\/doi.org\/10.1007\/s12015-025-11005-4","relation":{},"ISSN":["2629-3269","2629-3277"],"issn-type":[{"value":"2629-3269","type":"print"},{"value":"2629-3277","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,13]]},"assertion":[{"value":"14 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 October 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Research involving human material has been approved by the Institutional Review Board of Taipei Medical University (Approval No. N202203070). All human participants provided informed consent for tooth donation. Animal studies were approved by the Institutional Animal Care and Use Committee of Taipei Medical University, Taipei, Taiwan (Approval No. LAC-2022-0020).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Statement"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}