{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T11:32:52Z","timestamp":1793964772633,"version":"4.8.0"},"reference-count":167,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,29]],"date-time":"2023-06-29T00:00:00Z","timestamp":1687996800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"CIBER \u201cFragilidad y Envejecimiento Saludable\u201d (CIBERFES) of \u201cInstituto de Salud Carlos III\u201d (ISCIII)","doi-asserted-by":"publisher","award":["PI18\/01659"],"award-info":[{"award-number":["PI18\/01659"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"CIBER \u201cFragilidad y Envejecimiento Saludable\u201d (CIBERFES) of \u201cInstituto de Salud Carlos III\u201d (ISCIII)","doi-asserted-by":"publisher","award":["PI21\/01935"],"award-info":[{"award-number":["PI21\/01935"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Bone metabolism is regulated by osteoblasts, osteoclasts, osteocytes, and stem cells. Pathologies such as osteoporosis, osteoarthritis, osteonecrosis, and traumatic fractures require effective treatments that favor bone formation and regeneration. Among these, cell therapy based on mesenchymal stem cells (MSC) has been proposed. MSC are osteoprogenitors, but their regenerative activity depends in part on their paracrine properties. These are mainly mediated by extracellular vesicle (EV) secretion. EV modulates regenerative processes such as inflammation, angiogenesis, cell proliferation, migration, and differentiation. Thus, MSC-EV are currently an important tool for the development of cell-free therapies in regenerative medicine. This review describes the current knowledge of the effects of MSC-EV in the different phases of bone regeneration. MSC-EV has been used by intravenous injection, directly or in combination with different types of biomaterials, in preclinical models of bone diseases. They have shown great clinical potential in regenerative medicine applied to bone. These findings should be confirmed through standardization of protocols, a better understanding of the mechanisms of action, and appropriate clinical trials. All that will allow the translation of such cell-free therapy to human clinic applications.<\/jats:p>","DOI":"10.3390\/jcm12134385","type":"journal-article","created":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T01:02:41Z","timestamp":1688086961000},"page":"4385","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Clinical Potential of Mesenchymal Stem Cell-Derived Exosomes in Bone Regeneration"],"prefix":"10.3390","volume":"12","author":[{"given":"B\u00e1rbara","family":"Torrecillas-Baena","sequence":"first","affiliation":[{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Endocrinolog\u00eda y Nutrici\u00f3n-GC17, Instituto Maim\u00f3nides de Investigaci\u00f3n Biom\u00e9dica de C\u00f3rdoba (IMIBIC), Hospital Universitario Reina Sof\u00eda, 14004 C\u00f3rdoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Pulido-Escribano","sequence":"additional","affiliation":[{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Endocrinolog\u00eda y Nutrici\u00f3n-GC17, Instituto Maim\u00f3nides de Investigaci\u00f3n Biom\u00e9dica de C\u00f3rdoba (IMIBIC), Hospital Universitario Reina Sof\u00eda, 14004 C\u00f3rdoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Dorado","sequence":"additional","affiliation":[{"name":"Department Bioqu\u00edmica y Biolog\u00eda Molecular, Campus Rabanales C6-1-E17, Campus de Excelencia Internacional Agroalimentario (ceiA3), Universidad de C\u00f3rdoba, 14071 C\u00f3rdoba, Spain"},{"name":"CIBER de Fragilidad y Envejecimiento Saludable (CIBERFES), 14004 C\u00f3rdoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda \u00c1ngeles","family":"G\u00e1lvez-Moreno","sequence":"additional","affiliation":[{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Endocrinolog\u00eda y Nutrici\u00f3n-GC17, Instituto Maim\u00f3nides de Investigaci\u00f3n Biom\u00e9dica de C\u00f3rdoba (IMIBIC), Hospital Universitario Reina Sof\u00eda, 14004 C\u00f3rdoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Camacho-Cardenosa","sequence":"additional","affiliation":[{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Endocrinolog\u00eda y Nutrici\u00f3n-GC17, Instituto Maim\u00f3nides de Investigaci\u00f3n Biom\u00e9dica de C\u00f3rdoba (IMIBIC), Hospital Universitario Reina Sof\u00eda, 14004 C\u00f3rdoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8520-8278","authenticated-orcid":false,"given":"Antonio","family":"Casado-D\u00edaz","sequence":"additional","affiliation":[{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Endocrinolog\u00eda y Nutrici\u00f3n-GC17, Instituto Maim\u00f3nides de Investigaci\u00f3n Biom\u00e9dica de C\u00f3rdoba (IMIBIC), Hospital Universitario Reina Sof\u00eda, 14004 C\u00f3rdoba, Spain"},{"name":"CIBER de Fragilidad y Envejecimiento Saludable (CIBERFES), 14004 C\u00f3rdoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s12938-023-01096-w","article-title":"Human cells with osteogenic potential in bone tissue research","volume":"22","author":"Dvorakova","year":"2023","journal-title":"Biomed. Eng. Online"},{"key":"ref_2","first-page":"421746","article-title":"Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells","volume":"2015","author":"Sasso","year":"2015","journal-title":"Biomed Res. Int."},{"key":"ref_3","first-page":"1","article-title":"The Cells of Bone and Their Interactions","volume":"Volume 262","author":"Ansari","year":"2020","journal-title":"Handbook of Experimental Pharmacology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.1038\/s12276-022-00899-6","article-title":"Neurovascular coupling in bone regeneration","volume":"54","author":"Qin","year":"2022","journal-title":"Exp. Mol. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.actbio.2022.09.023","article-title":"Neuro-bone tissue engineering: Multiple potential translational strategies between nerve and bone","volume":"153","author":"Zhang","year":"2022","journal-title":"Acta Biomater."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1146\/annurev-pathol-011110-130203","article-title":"Disorders of Bone Remodeling","volume":"6","author":"Feng","year":"2011","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Qi, J., Yu, T., Hu, B., Wu, H., and Ouyang, H. (2021). Current biomaterial-based bone tissue engineering and translational medicine. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910233"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1002\/jbm.a.36518","article-title":"Extracellular vesicle and mesenchymal stem cells in bone regeneration: Recent progress and perspectives","volume":"107","author":"Chu","year":"2019","journal-title":"J. Biomed. Mater. Res.\u2014Part A"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Zhou, Y., Yamamoto, Y., Xiao, Z., and Ochiya, T. (2019). The immunomodulatory functions of mesenchymal stromal\/stem cells mediated via paracrine activity. J. Clin. Med., 8.","DOI":"10.3390\/jcm8071025"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"352","DOI":"10.3389\/fbioe.2019.00352","article-title":"Mesenchymal Stromal Cell-Based Bone Regeneration Therapies: From Cell Transplantation and Tissue Engineering to Therapeutic Secretomes and Extracellular Vesicles","volume":"7","author":"Traweger","year":"2019","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1196\/annals.1365.035","article-title":"Bone Remodeling","volume":"1092","author":"Hadjidakis","year":"2006","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1152\/physiol.00061.2014","article-title":"Physiological bone remodeling: Systemic regulation and growth factor involvement","volume":"31","author":"Siddiqui","year":"2016","journal-title":"Physiology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1634\/stemcells.19-3-180","article-title":"Bone Marrow Stromal Stem Cells: Nature, Biology, and Potential Applications","volume":"19","author":"Bianco","year":"2001","journal-title":"Stem Cells"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1126\/science.289.5484.1504","article-title":"Bone resorption by osteoclasts","volume":"289","author":"Teitelbaum","year":"2000","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/BF02555002","article-title":"Electron microscopy of developing calvaria reveals images that suggest that osteoclasts engulf and destroy osteocytes during bone resorption","volume":"46","author":"Elmardi","year":"1990","journal-title":"Calcif. Tissue Int."},{"key":"ref_16","first-page":"1017","article-title":"Osteoporosis: Pathophysiology and therapeutic options","volume":"19","author":"Dovjak","year":"2020","journal-title":"EXCLI J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1001\/jama.292.4.490","article-title":"Clinical Implications of the Osteoprotegerin\/RANKL\/RANK System for Bone and Vascular Diseases","volume":"292","author":"Hofbauer","year":"2004","journal-title":"JAMA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1172\/JCI32518","article-title":"Vascular biology and bone formation: Hints from HIF","volume":"117","author":"Towler","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S0070-2153(04)65006-X","article-title":"Multiple Roles of Vascular Endothelial Growth Factor (VEGF) in Skeletal Development, Growth, and Repair","volume":"65","author":"Zelzer","year":"2004","journal-title":"Curr. Top. Dev. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1172\/JCI31581","article-title":"The hypoxia-inducible factor \u03b1 pathway couples angiogenesis to osteogenesis during skeletal development","volume":"117","author":"Wang","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.gde.2003.08.001","article-title":"Mesoangioblasts\u2014Vascular progenitors for extravascular mesodermal tissues","volume":"13","author":"Cossu","year":"2003","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1002\/jor.23460","article-title":"Fracture healing physiology and the quest for therapies for delayed healing and nonunion","volume":"35","author":"Kostenuik","year":"2017","journal-title":"J. Orthop. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/S8756-3282(01)00608-1","article-title":"Prevention of fracture healing in rats by an inhibitor of angiogenesis","volume":"29","author":"Hausman","year":"2001","journal-title":"Bone"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1002\/jor.20264","article-title":"Ischemia leads to delayed union during fracture healing: A mouse model","volume":"25","author":"Lu","year":"2007","journal-title":"J. Orthop. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/8756-3282(93)90251-5","article-title":"The effects of growth hormone on fracture healing in rats: A histological description","volume":"14","author":"Mosekilde","year":"1993","journal-title":"Bone"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.rcl.2010.02.014","article-title":"Physiology of Bone Loss","volume":"48","author":"Clarke","year":"2010","journal-title":"Radiol. Clin. N. Am."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1050489","DOI":"10.3389\/fcell.2022.1050489","article-title":"Declined adipogenic potential of senescent MSCs due to shift in insulin signaling and altered exosome cargo","volume":"10","author":"Voynova","year":"2022","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/s41586-019-1365-2","article-title":"From discoveries in ageing research to therapeutics for healthy ageing","volume":"571","author":"Campisi","year":"2019","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1038\/nature13193","article-title":"The role of senescent cells in ageing","volume":"509","year":"2014","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"32","DOI":"10.5966\/sctm.2013-0014","article-title":"Adipose-Derived Mesenchymal Stromal Cells From Aged Patients With Coronary Artery Disease Keep Mesenchymal Stromal Cell Properties but Exhibit Characteristics of Aging and Have Impaired Angiogenic Potential","volume":"3","author":"Efimenko","year":"2014","journal-title":"Stem Cells Transl. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.addr.2012.07.010","article-title":"The role of exosomes and microRNAs in senescence and aging","volume":"65","author":"Xu","year":"2013","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1002\/stem.2756","article-title":"Intercellular Transfer of Microvesicles from Young Mesenchymal Stromal Cells Rejuvenates Aged Murine Hematopoietic Stem Cells","volume":"36","author":"Kulkarni","year":"2018","journal-title":"Stem Cells"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"576176","DOI":"10.3389\/fcell.2020.576176","article-title":"Mesenchymal Stromal Cells as Critical Contributors to Tissue Regeneration","volume":"8","author":"Sagaradze","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/s41574-020-0335-y","article-title":"The role of cellular senescence in ageing and endocrine disease","volume":"16","author":"Khosla","year":"2020","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1172\/JCI64098","article-title":"Cellular senescence and the senescent secretory phenotype: Therapeutic opportunities","volume":"123","author":"Tchkonia","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1016\/j.bioactmat.2020.08.014","article-title":"Advancing application of mesenchymal stem cell-based bone tissue regeneration","volume":"6","author":"Shang","year":"2020","journal-title":"Bioact. Mater."},{"key":"ref_37","first-page":"393","article-title":"The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells","volume":"3","author":"Friedenstein","year":"1970","journal-title":"Cell Tissue Kinet."},{"key":"ref_38","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_39","doi-asserted-by":"crossref","unstructured":"Han, Y., Li, X., Zhang, Y., Han, Y., Chang, F., and Ding, J. (2019). Mesenchymal Stem Cells for Regenerative Medicine. Cells, 8.","DOI":"10.3390\/cells8080886"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.4252\/wjsc.v12.i12.1529","article-title":"Mesenchymal stem cells se-cretome: The cornerstone of cell-free regenerative medicine","volume":"12","author":"Dotta","year":"2020","journal-title":"World J. Stem Cells"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1186\/s13287-018-0791-7","article-title":"Mesenchymal stem cell-derived extracellular vesicles: Novel frontiers in regenerative medicine","volume":"9","author":"Keshtkar","year":"2018","journal-title":"Stem Cell Res. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nrm.2017.125","article-title":"Shedding light on the cell biology of extracellular vesicles","volume":"19","author":"Raposo","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"836","DOI":"10.7150\/ijbs.14809","article-title":"Exosomes secreted by human-induced pluripotent stem cell-derived mesenchymal stem cells repair critical-sized bone defects through enhanced angiogenesis and osteogenesis in osteoporotic rats","volume":"12","author":"Qi","year":"2016","journal-title":"Int. J. Biol. Sci."},{"key":"ref_44","first-page":"45622","article-title":"Extracellular Vesicle-functionalized Decalcified Bone Matrix Scaffolds with Enhanced Pro-angiogenic and Pro-bone Regeneration Activities","volume":"7","author":"Xie","year":"2017","journal-title":"Sci. Reports"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.actbio.2017.08.030","article-title":"Regenerating bone with bioactive glass scaffolds: A review of in vivo studies in bone defect models","volume":"62","author":"Roether","year":"2017","journal-title":"Acta Biomater."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1089\/ten.teb.2012.0437","article-title":"Three-dimensional scaffolds for tissue engineering applications: Role of porosity and pore size","volume":"19","author":"Loh","year":"2013","journal-title":"Tissue Eng. Part B Rev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"725","DOI":"10.7150\/thno.39167","article-title":"Mesenchymal stem cell-loaded thermosensitive hydroxypropyl chitin hydrogel combined with a three-dimensional-printed poly(\u03b5-caprolactone)\/nano-hydroxyapatite scaffold to repair bone defects via osteogenesis, angiogenesis and immunomodulation","volume":"10","author":"Ji","year":"2020","journal-title":"Theranostics"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/s41577-022-00763-8","article-title":"The roles of extracellular vesicles in the immune system","volume":"23","author":"Buzas","year":"2023","journal-title":"Nat. Rev. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Harrell, C.R., Jovicic, N., Djonov, V., Arsenijevic, N., and Volarevic, V. (2019). Mesenchymal stem cell-derived exosomes and other extracellular vesicles as new remedies in the therapy of inflammatory diseases. Cells, 8.","DOI":"10.3390\/cells8121605"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.devcel.2020.11.017","article-title":"Embryonic Stem Cell-Derived Extracellular Vesicles Maintain ESC Stemness by Activating FAK","volume":"56","author":"Hur","year":"2021","journal-title":"Dev. Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"18472","DOI":"10.1021\/acsami.0c22671","article-title":"Umbilical Mesenchymal Stem Cell-Derived Exosome-Encapsulated Hydrogels Accelerate Bone Repair by Enhancing Angiogenesis","volume":"13","author":"Zhang","year":"2021","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/ncomms1285","article-title":"Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells","volume":"2","author":"Mittelbrunn","year":"2011","journal-title":"Nat. Commun."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1016\/j.immuni.2019.01.010","article-title":"Specific Decrease in B-Cell-Derived Extracellular Vesicles Enhances Post-Chemotherapeutic CD8 + T Cell Responses","volume":"50","author":"Zhang","year":"2019","journal-title":"Immunity"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1016\/j.ymthe.2019.05.019","article-title":"Extracellular Vesicles from Albumin-Induced Tubular Epithelial Cells Promote the M1 Macrophage Phenotype by Targeting Klotho","volume":"27","author":"Jia","year":"2019","journal-title":"Mol. Ther."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1007\/s00018-018-2983-9","article-title":"Endothelial cell apoptosis and the role of endothelial cell-derived extracellular vesicles in the progression of atherosclerosis","volume":"76","author":"Paone","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1186\/s12931-020-01346-8","article-title":"Extracellular vesicles from mast cells induce mesenchymal transition in airway epithelial cells","volume":"21","author":"Yin","year":"2020","journal-title":"Respir. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3456","DOI":"10.1016\/j.neuron.2021.08.011","article-title":"Oligodendrocytes enhance axonal energy metabolism by deacetylation of mitochondrial proteins through transcellular delivery of SIRT2","volume":"109","author":"Chamberlain","year":"2021","journal-title":"Neuron"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Gao, S., Bai, L., Jia, S., and Meng, C. (2022). Small Extracellular Vesicles of M1-BV2 Microglia Induce Neuronal PC12 Cells Apoptosis via the Competing Endogenous Mechanism of CircRNAs. Genes, 13.","DOI":"10.3390\/genes13091603"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"749","DOI":"10.2337\/db19-0432","article-title":"Exosomes derived from Schwann cells ameliorate peripheral neuropathy in type 2 diabetic mice","volume":"69","author":"Wang","year":"2020","journal-title":"Diabetes"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1016\/j.ccell.2016.10.009","article-title":"Extracellular Vesicles in Cancer: Cell-to-Cell Mediators of Metastasis","volume":"30","author":"Becker","year":"2016","journal-title":"Cancer Cell"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2402","DOI":"10.1038\/s41467-019-10360-4","article-title":"Extracellular vesicles from CLEC2-activated platelets enhance dengue virus-induced lethality via CLEC5A\/TLR2","volume":"10","author":"Sung","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"27066","DOI":"10.3402\/jev.v4.27066","article-title":"Biological properties of extracellular vesicles and their physiological functions","volume":"4","author":"Siljander","year":"2015","journal-title":"J. Extracell. Vesicles"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"146","DOI":"10.3389\/fbioe.2020.00146","article-title":"Extracellular Vesicles Derived From Mesenchymal Stem Cells (MSC) in Regenerative Medicine: Applications in Skin Wound Healing","volume":"8","author":"Dorado","year":"2020","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41556-018-0250-9","article-title":"Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication","volume":"21","author":"Mathieu","year":"2019","journal-title":"Nat. Cell Biol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Akbar, A., Malekian, F., Baghban, N., Kodam, S.P., and Ullah, M. (2022). Methodologies to Isolate and Purify Clinical Grade Extracellular Vesicles for Medical Applications. Cells, 11.","DOI":"10.3390\/cells11020186"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Gurunathan, S., Kang, M.H., Jeyaraj, M., Qasim, M., and Kim, J.H. (2019). Review of the isolation, characterization, biological function, and multifarious therapeutic approaches of exosomes. Cells, 8.","DOI":"10.3390\/cells8040307"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"453","DOI":"10.4252\/wjsc.v14.i7.453","article-title":"Role of hypoxia preconditioning in therapeutic potential of mesenchymal stem-cell-derived extracellular vesicles","volume":"14","author":"Dorado","year":"2022","journal-title":"World J. Stem Cells"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Vizoso, F.J., Eiro, N., Cid, S., Schneider, J., and Perez-Fernandez, R. (2017). Mesenchymal stem cell secretome: Toward cell-free therapeutic strategies in regenerative medicine. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18091852"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"70","DOI":"10.3350\/cmh.2020.0194","article-title":"The development of mesenchymal stem cell therapy in the present, and the perspective of cell-free therapy in the future","volume":"27","author":"Watanabe","year":"2020","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"9742765","DOI":"10.1155\/2019\/9742765","article-title":"Exosomes Derived from Human Bone Marrow Mesenchymal Stem Cells Stimulated by Deferoxamine Accelerate Cutaneous Wound Healing by Promoting Angiogenesis","volume":"2019","author":"Ding","year":"2019","journal-title":"Biomed Res. Int."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"113961","DOI":"10.1016\/j.addr.2021.113961","article-title":"Dosing extracellular vesicles","volume":"178","author":"Gupta","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1038\/mt.2015.44","article-title":"Mesenchymal stem cell-derived extracellular vesicles: Toward cell-free therapeutic applications","volume":"23","author":"Rani","year":"2015","journal-title":"Mol. Ther."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1001\/jamaoncol.2016.0097","article-title":"A novel urine exosome gene expression assay to predict high-grade prostate cancer at initial biopsy","volume":"2","author":"McKiernan","year":"2016","journal-title":"JAMA Oncol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"382","DOI":"10.3389\/fendo.2020.00382","article-title":"Urinary Exosomal Thyroglobulin in Thyroid Cancer Patients With Post-ablative Therapy: A New Biomarker in Thyroid Cancer","volume":"11","author":"Huang","year":"2020","journal-title":"Front. Endocrinol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1093\/abbs\/gmaa028","article-title":"Exosomal piRNA profiling revealed unique circulating piRNA signatures of cholangiocarcinoma and gallbladder carcinoma","volume":"52","author":"Gu","year":"2021","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Dobra, G., Bukva, M., Szabo, Z., Bruszel, B., Harmati, M., Gyukity-Sebestyen, E., Jenei, A., Szucs, M., Horvath, P., and Biro, T. (2020). Small extracellular vesicles isolated from serum may serve as signal-enhancers for the monitoring of cns tumors. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21155359"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e21895","DOI":"10.1096\/fj.202100787R","article-title":"Plasma extracellular vesicles tau and \u03b2-amyloid as biomarkers of cognitive dysfunction of Parkinson\u2019s disease","volume":"35","author":"Chung","year":"2021","journal-title":"FASEB J."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1186\/s13287-022-02900-5","article-title":"Nebulized exosomes derived from allogenic adipose tissue mesenchymal stromal cells in patients with severe COVID-19: A pilot study","volume":"13","author":"Zhu","year":"2022","journal-title":"Stem Cell Res. Ther."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3153891","DOI":"10.1155\/2020\/3153891","article-title":"Molecular and Cellular Mechanisms Responsible for Beneficial Effects of Mesenchymal Stem Cell-Derived Product \u201cexo-d-MAPPS\u201d in Attenuation of Chronic Airway Inflammation","volume":"2020","author":"Harrell","year":"2020","journal-title":"Anal. Cell. Pathol."},{"key":"ref_80","unstructured":"Sheen, J.R., and Garla, V.V. (2022). Fracture Healing Overview, StatPearls Publishing."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1002\/jor.24170","article-title":"Cellular biology of fracture healing","volume":"37","author":"Bahney","year":"2019","journal-title":"J. Orthop. Res."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Vig, S., and Fernandes, M.H. (2022). Bone Cell Exosomes and Emerging Strategies in Bone Engineering. Biomedicines, 10.","DOI":"10.3390\/biomedicines10040767"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/nrrheum.2014.164","article-title":"Fracture healing: Mechanisms and interventions","volume":"11","author":"Einhorn","year":"2014","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_84","first-page":"28","article-title":"Inflammation, ageing, and bone regeneration","volume":"10","author":"Gibon","year":"2017","journal-title":"J. Orthop. Transl."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"3483","DOI":"10.2147\/IJN.S248741","article-title":"Osteoimmune modulation and guided steogenesis promoted by barrier membranes incorporated with s-nitrosoglutathione (Gsno) and mesenchymal stem cell-derived exosomes","volume":"15","author":"Wang","year":"2020","journal-title":"Int. J. Nanomed."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1002\/term.2947","article-title":"Immunoregulatory role of exosomes derived from differentiating mesenchymal stromal cells on inflammation and osteogenesis","volume":"13","author":"Wei","year":"2019","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"3178","DOI":"10.1039\/C9BM00426B","article-title":"Tauroursodeoxycholic acid (TUDCA) counters osteoarthritis by regulating intracellular cholesterol levels and membrane fluidity of degenerated chondrocytes","volume":"7","author":"Arai","year":"2019","journal-title":"Biomater. Sci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jconrel.2022.12.053","article-title":"Generation of bioactive MSC-EVs for bone tissue regeneration by tauroursodeoxycholic acid treatment","volume":"354","author":"Cha","year":"2023","journal-title":"J. Control. Release"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"878194","DOI":"10.3389\/fimmu.2022.878194","article-title":"Extracellular Vesicles From TNF\u03b1 Preconditioned MSCs: Effects on Immunomodulation and Bone Regeneration","volume":"13","author":"Kang","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1038\/s41577-019-0178-8","article-title":"Osteoimmunology: Evolving concepts in bone\u2013immune interactions in health and disease","volume":"19","author":"Tsukasaki","year":"2019","journal-title":"Nat. Rev. Immunol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1089\/ten.tea.2016.0548","article-title":"Priming Adipose Stem Cells with Tumor Necrosis Factor-Alpha Preconditioning Potentiates Their Exosome Efficacy for Bone Regeneration","volume":"23","author":"Lu","year":"2017","journal-title":"Tissue Eng.\u2014Part A"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/s13075-022-02778-x","article-title":"PTH (1-34) enhances the therapeutic effect of bone marrow mesenchymal stem cell-derived exosomes by inhibiting proinflammatory cytokines expression on OA chondrocyte repair in vitro","volume":"24","author":"Shao","year":"2022","journal-title":"Arthritis Res. Ther."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.actbio.2019.12.020","article-title":"Hypoxic mesenchymal stem cell-derived exosomes promote bone fracture healing by the transfer of miR-126","volume":"103","author":"Liu","year":"2020","journal-title":"Acta Biomater."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.bioactmat.2022.10.001","article-title":"Small extracellular vesicles derived from hypoxic preconditioned dental pulp stem cells ameliorate inflammatory osteolysis by modulating macrophage polarization and osteoclastogenesis","volume":"22","author":"Tian","year":"2023","journal-title":"Bioact. Mater."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"6655225","DOI":"10.1155\/2021\/6655225","article-title":"Exosomes Secreted from Hypoxia-Preconditioned Mesenchymal Stem Cells Prevent Steroid-Induced Osteonecrosis of the Femoral Head by Promoting Angiogenesis in Rats","volume":"2021","author":"Yuan","year":"2021","journal-title":"Biomed Res. Int."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"639","DOI":"10.7150\/ijbs.14025","article-title":"Dimethyloxaloylglycine Promotes the Angiogenic Activity of Mesenchymal Stem Cells Derived from iPSCs via Activation of the PI3K\/Akt Pathway for Bone Regeneration","volume":"12","author":"Zhang","year":"2016","journal-title":"Int. J. Biol. Sci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1186\/s13287-019-1410-y","article-title":"Dimethyloxaloylglycine-stimulated human bone marrow mesenchymal stem cell-derived exosomes enhance bone regeneration through angiogenesis by targeting the AKT\/mTOR pathway","volume":"10","author":"Liang","year":"2019","journal-title":"Stem Cell Res. Ther."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"829136","DOI":"10.3389\/fbioe.2021.829136","article-title":"Bone Mesenchymal Stem Cell-Derived sEV-Encapsulated Thermosensitive Hydrogels Accelerate Osteogenesis and Angiogenesis by Release of Exosomal miR-21","volume":"9","author":"Wu","year":"2022","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"121438","DOI":"10.1016\/j.biomaterials.2022.121438","article-title":"Bioactive glass nanoparticles inhibit osteoclast differentiation and osteoporotic bone loss by activating lncRNA NRON expression in the extracellular vesicles derived from bone marrow mesenchymal stem cells","volume":"283","author":"Yang","year":"2022","journal-title":"Biomaterials"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Yahao, G., and Xinjia, W. (2021). The Role and Mechanism of Exosomes from Umbilical Cord Mesenchymal Stem Cells in Inducing Osteogenesis and Preventing Osteoporosis. Cell Transplant., 30.","DOI":"10.1177\/09636897211057465"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.actbio.2020.12.046","article-title":"Exosomes from TNF-\u03b1-treated human gingiva-derived MSCs enhance M2 macrophage polarization and inhibit periodontal bone loss","volume":"122","author":"Nakao","year":"2021","journal-title":"Acta Biomater."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"9128","DOI":"10.18632\/aging.102379","article-title":"Mesenchymal stem cell senescence alleviates their intrinsic and seno-suppressive paracrine properties contributing to osteoarthritis development","volume":"11","author":"Malaise","year":"2019","journal-title":"Aging"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"9688138","DOI":"10.1155\/2021\/9688138","article-title":"A Comparative Study on the Effect of Exosomes Secreted by Mesenchymal Stem Cells Derived from Adipose and Bone Marrow Tissues in the Treatment of Osteoarthritis-Induced Mouse Model","volume":"2021","author":"Fazaeli","year":"2021","journal-title":"Biomed Res. Int."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Kwon, D.G., Kim, M.K., Jeon, Y.S., Nam, Y.C., Park, J.S., and Ryu, D.J. (2022). State of the Art: The Immunomodulatory Role of MSCs for Osteoarthritis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031618"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1111\/evj.13537","article-title":"Extracellular vesicles from equine mesenchymal stem cells decrease inflammation markers in chondrocytes in vitro","volume":"54","author":"Baratta","year":"2022","journal-title":"Equine Vet. J."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s12951-021-01236-1","article-title":"Anti-inflammatory and immunomodulatory effects of the extracellular vesicles derived from human umbilical cord mesenchymal stem cells on osteoarthritis via M2 macrophages","volume":"20","author":"Li","year":"2022","journal-title":"J. Nanobiotechnol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.4049\/jimmunol.1601515","article-title":"Akt Signaling Pathway in Macrophage Activation and M1\/M2 Polarization","volume":"198","author":"Vergadi","year":"2017","journal-title":"J. Immunol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.biomaterials.2019.02.006","article-title":"MSC exosomes alleviate temporomandibular joint osteoarthritis by attenuating inflammation and restoring matrix homeostasis","volume":"200","author":"Zhang","year":"2019","journal-title":"Biomaterials"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"7734","DOI":"10.1111\/jcmm.16654","article-title":"Bone marrow mesenchymal stem cell\u2013derived exosomal miR-206 promotes osteoblast proliferation and differentiation in osteoarthritis by reducing Elf3","volume":"25","author":"Huang","year":"2021","journal-title":"J. Cell. Mol. Med."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"105946","DOI":"10.1016\/j.intimp.2019.105946","article-title":"Human bone mesenchymal stem cells-derived exosomes overexpressing microRNA-26a-5p alleviate osteoarthritis via down-regulation of PTGS2","volume":"78","author":"Jin","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"906","DOI":"10.7150\/thno.20746","article-title":"Mesenchymal stromal\/stem cell-derived extracellular vesicles promote human cartilage regeneration in vitro","volume":"8","author":"Vonk","year":"2018","journal-title":"Theranostics"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"7197598","DOI":"10.1155\/2017\/7197598","article-title":"Extracellular vesicles from adipose-derived mesenchymal stem cells downregulate senescence features in osteoarthritic osteoblasts","volume":"2017","author":"Alcaraz","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"107824","DOI":"10.1016\/j.intimp.2021.107824","article-title":"Low-intensity pulsed ultrasound promotes osteoarthritic cartilage regeneration by BMSC-derived exosomes via modulating the NF-\u03baB signaling pathway","volume":"97","author":"Liao","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"ref_114","first-page":"3900","article-title":"Research on the correlation of diabetes mellitus complicated with osteoporosis with lipid metabolism, adipokines and inflammatory factors and its regression analysis","volume":"21","author":"Chen","year":"2017","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.jbiosc.2021.02.007","article-title":"Exosomes from adipose derived mesenchymal stem cells alleviate diabetic osteoporosis in rats through suppressing NLRP3 inflammasome activation in osteoclasts","volume":"131","author":"Zhang","year":"2021","journal-title":"J. Biosci. Bioeng."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1186\/s12951-021-01015-y","article-title":"A novel delivery nanobiotechnology: Engineered miR-181b exosomes improved osteointegration by regulating macrophage polarization","volume":"19","author":"Liu","year":"2021","journal-title":"J. Nanobiotechnol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"rbab010","DOI":"10.1093\/rb\/rbab010","article-title":"Surface engineering of titania nanotubes incorporated with double-layered extracellular vesicles to modulate inflammation and osteogenesis","volume":"8","author":"Zhao","year":"2021","journal-title":"Regen. Biomater."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"2706","DOI":"10.1242\/dev.136861","article-title":"Blood vessel formation and function in bone","volume":"143","author":"Sivaraj","year":"2016","journal-title":"Development"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00774-017-0860-5","article-title":"Extracellular vesicle-mediated bone metabolism in the bone microenvironment","volume":"36","author":"Li","year":"2018","journal-title":"Bone Miner. Metab."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"674084","DOI":"10.3389\/fcell.2021.674084","article-title":"Cross-Talk Between Mesenchymal Stromal Cells (MSCs) and Endothelial Progenitor Cells (EPCs) in Bone Regeneration","volume":"9","author":"Bouland","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.yexcr.2018.06.003","article-title":"Exosomes derived from endothelial progenitor cells ameliorate acute lung injury by transferring miR-126","volume":"370","author":"Wu","year":"2018","journal-title":"Exp. Cell Res."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.bone.2016.06.013","article-title":"The roles of vascular endothelial growth factor in bone repair and regeneration","volume":"91","author":"Hu","year":"2016","journal-title":"Bone"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Takeuchi, R., Katagiri, W., Endo, S., and Kobayashi, T. (2019). Exosomes from conditioned media of bone marrow-derived mesenchymal stem cells promote bone regeneration by enhancing angiogenesis. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0225472"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.bbrc.2007.08.099","article-title":"Osteoblast-specific Angiopoietin 1 overexpression increases bone mass","volume":"362","author":"Suzuki","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"7715","DOI":"10.7150\/thno.58410","article-title":"Exosomal lncRNA-H19 promotes osteogenesis and angiogenesis through mediating Angpt1\/Tie2-NO signaling in CBS-heterozygous mice","volume":"11","author":"Behera","year":"2021","journal-title":"Theranostics"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"6201","DOI":"10.2147\/IJN.S389471","article-title":"Small Extracellular Vesicles Released from Bioglass\/Hydrogel Scaffold Promote Vascularized Bone Regeneration by Transferring miR-23a-3p","volume":"17","author":"Hu","year":"2022","journal-title":"Int. J. Nanomed."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"113026","DOI":"10.1016\/j.yexcr.2022.113026","article-title":"Extracellular vesicles-encapsulated microRNA-29b-3p from bone marrow-derived mesenchymal stem cells promotes fracture healing via modulation of the PTEN\/PI3K\/AKT axis","volume":"412","author":"Yang","year":"2022","journal-title":"Exp. Cell Res."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1038\/cdd.2008.12","article-title":"Biology of HIF-1\u03b1","volume":"15","author":"Weidemann","year":"2008","journal-title":"Cell Death Differ."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"120646","DOI":"10.1016\/j.biomaterials.2020.120646","article-title":"Unlocking mammalian regeneration through hypoxia inducible factor one alpha signaling","volume":"269","author":"DeFrates","year":"2021","journal-title":"Biomaterials"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.actbio.2022.07.015","article-title":"Small extracellular vesicles derived from hypoxic mesenchymal stem cells promote vascularized bone regeneration through the miR-210-3p\/EFNA3\/PI3K pathway","volume":"150","author":"Zhuang","year":"2022","journal-title":"Acta Biomater."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1002\/cbin.10869","article-title":"Exosomes secreted from mutant-HIF-1\u03b1-modified bone-marrow-derived mesenchymal stem cells attenuate early steroid-induced avascular necrosis of femoral head in rabbit","volume":"41","author":"Li","year":"2017","journal-title":"Cell Biol. Int."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"e12570","DOI":"10.1111\/cpr.12570","article-title":"Exosomes from human umbilical cord mesenchymal stem cells enhance fracture healing through HIF-1\u03b1-mediated promotion of angiogenesis in a rat model of stabilized fracture","volume":"52","author":"Zhang","year":"2019","journal-title":"Cell Prolif."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.semcdb.2018.08.007","article-title":"Extracellular matrix scaffolding in angiogenesis and capillary homeostasis","volume":"89","author":"Marchand","year":"2019","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.bioactmat.2021.10.021","article-title":"Nidogen1-enriched extracellular vesicles accelerate angiogenesis and bone regeneration by targeting Myosin-10 to regulate endothelial cell adhesion","volume":"12","author":"Cheng","year":"2022","journal-title":"Bioact. Mater."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"dev199908","DOI":"10.1242\/dev.199908","article-title":"The origins and roles of osteoclasts in bone development, homeostasis and repair","volume":"149","author":"Yahara","year":"2022","journal-title":"Development"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1002\/bdrc.21047","article-title":"Osteoblast recruitment to sites of bone formation in skeletal development, homeostasis, and regeneration","volume":"99","author":"Dirckx","year":"2013","journal-title":"Birth Defects Res. Part C\u2014Embryo Today Rev."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1177\/0022034518764411","article-title":"Emerging Role of Extracellular Vesicles in Bone Remodeling","volume":"97","author":"Liu","year":"2018","journal-title":"J. Dent. Res."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.bone.2018.05.019","article-title":"Defining osteoblast and adipocyte lineages in the bone marrow","volume":"118","author":"Pierce","year":"2019","journal-title":"Bone"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"45","DOI":"10.2147\/DDDT.S178698","article-title":"Osteogenic effect of bone marrow mesenchymal stem cell-derived exosomes on steroid-induced osteonecrosis of the femoral head","volume":"13","author":"Fang","year":"2019","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"2293","DOI":"10.7150\/thno.39238","article-title":"Human umbilical cord mesenchymal stromal cells-derived extracellular vesicles exert potent bone protective effects by CLEC11A-mediated regulation of bone metabolism","volume":"10","author":"Hu","year":"2020","journal-title":"Theranostics"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"27","DOI":"10.7554\/eLife.18782","article-title":"Clec11a\/osteolectin is an osteogenic growth factor that promotes the maintenance of the adult skeleton","volume":"5","author":"Yue","year":"2016","journal-title":"Elife"},{"key":"ref_142","first-page":"811","article-title":"Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Enhance the Osteoblastic Differentiation of Periodontal Ligament Stem Cells Under High Glucose Conditions Through the PI3K\/AKT Signaling Pathway","volume":"35","author":"Yang","year":"2022","journal-title":"Biomed. Environ. Sci."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1038\/s41419-021-03430-3","article-title":"Role of microRNA-335 carried by bone marrow mesenchymal stem cells-derived extracellular vesicles in bone fracture recovery","volume":"12","author":"Hu","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1007\/s10753-021-01583-z","article-title":"Mesenchymal Stem Cell\u2013Derived Extracellular Vesicles Inhibit Osteoporosis via MicroRNA-27a-Induced Inhibition of DKK2-Mediated Wnt\/\u03b2-Catenin Pathway","volume":"45","author":"Wang","year":"2022","journal-title":"Inflammation"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1186\/s12951-021-00958-6","article-title":"Bone mesenchymal stem cells stimulation by magnetic nanoparticles and a static magnetic field: Release of exosomal miR-1260a improves osteogenesis and angiogenesis","volume":"19","author":"Wu","year":"2021","journal-title":"J. Nanobiotechnol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"21961","DOI":"10.1038\/srep21961","article-title":"Bone marrow stromal\/stem cell-derived extracellular vesicles regulate osteoblast activity and differentiation in vitro and promote bone regeneration in vivo","volume":"6","author":"Qin","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1186\/s13287-020-01707-6","article-title":"Extracellular vesicle-encapsulated miR-22-3p from bone marrow mesenchymal stem cell promotes osteogenic differentiation via FTO inhibition","volume":"11","author":"Zhang","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"119204","DOI":"10.1016\/j.lfs.2021.119204","article-title":"microRNA-935-modified bone marrow mesenchymal stem cells-derived exosomes enhance osteoblast proliferation and differentiation in osteoporotic rats","volume":"272","author":"Zhang","year":"2021","journal-title":"Life Sci."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1083\/jcb.201201057","article-title":"miR-34s inhibit osteoblast proliferation and differentiation in the mouse by targeting SATB2","volume":"197","author":"Wei","year":"2012","journal-title":"J. Cell Biol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/j.cell.2006.05.012","article-title":"SATB2 Is a Multifunctional Determinant of Craniofacial Patterning and Osteoblast Differentiation","volume":"125","author":"Dobreva","year":"2006","journal-title":"Cell"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"8777","DOI":"10.18632\/aging.102264","article-title":"LncRNA MALAT1 shuttled by bone marrow-derived mesenchymal stem cells-secreted exosomes alleviates osteoporosis through mediating microRNA-34c\/SATB2 axis","volume":"11","author":"Yang","year":"2019","journal-title":"Aging"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"2970","DOI":"10.1002\/jcb.25245","article-title":"The influence of MicroRNA-150 in Osteoblast Matrix Mineralization","volume":"116","author":"Dong","year":"2015","journal-title":"J. Cell. Biochem."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1089\/hum.2020.005","article-title":"Bone marrow mesenchymal stem cells-derived exosomal MicroRNA-150-3p promotes osteoblast proliferation and differentiation in osteoporosis","volume":"32","author":"Qiu","year":"2021","journal-title":"Hum. Gene Ther."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"20794","DOI":"10.1073\/pnas.0909311106","article-title":"A MicroRNA regulatory mechanism of osteoblast differentiation","volume":"106","author":"Inose","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"e12152","DOI":"10.1002\/jev2.12152","article-title":"Extracellular vesicles from adipose tissue-derived stem cells alleviate osteoporosis through osteoprotegerin and miR-21-5p","volume":"10","author":"Lee","year":"2021","journal-title":"J. Extracell. Vesicles"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.abb.2008.03.018","article-title":"Functions of RANKL\/RANK\/OPG in bone modeling and remodeling","volume":"473","author":"Boyce","year":"2008","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Su, P., Tian, Y., Yang, C., Ma, X., Wang, X., Pei, J., and Qian, A. (2018). Mesenchymal Stem Cell Migration during Bone Formation and Bone Diseases Therapy. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19082343"},{"key":"ref_158","first-page":"576","article-title":"Exosomes from gingival mesenchymal stem cells enhance migration and osteogenic differentiation of pre-osteoblasts","volume":"75","author":"Jiang","year":"2020","journal-title":"Pharmazie"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"519","DOI":"10.2147\/IJN.S346755","article-title":"Periodontal Ligament Stem Cell-Derived Small Extracellular Vesicles Embedded in Matrigel Enhance Bone Repair Through the Adenosine Receptor Signaling Pathway","volume":"17","author":"Zhao","year":"2022","journal-title":"Int. J. Nanomed."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.biomaterials.2015.02.064","article-title":"Emulating native periosteum cell population and subsequent paracrine factor production to promote tissue engineered periosteum-mediated allograft healing","volume":"52","author":"Hoffman","year":"2015","journal-title":"Biomaterials"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"21947","DOI":"10.1002\/jcp.28758","article-title":"Rat sinus mucosa- and periosteum-derived exosomes accelerate osteogenesis","volume":"234","author":"Sun","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"e48191","DOI":"10.7554\/eLife.48191","article-title":"Human perivascular stem cell-derived extracellular vesicles mediate bone repair","volume":"8","author":"Xu","year":"2019","journal-title":"Elife"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"11385","DOI":"10.1021\/acs.chemrev.0c01177","article-title":"Translational Applications of Hydrogels","volume":"121","author":"Correa","year":"2021","journal-title":"Chem. Rev."},{"key":"ref_164","first-page":"1123","article-title":"A smart magnetic hydrogel containing exosome promotes osteogeniccommitmentofhumanadipose-derivedmesenchymal stem cells","volume":"26","author":"Nkukar","year":"2022","journal-title":"Iran. J. Basic Med. Sci."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"6306","DOI":"10.1039\/C4CS00322E","article-title":"Emerging translational research on magnetic nanoparticles for regenerative medicine","volume":"44","author":"Gao","year":"2015","journal-title":"Chem. Soc. Rev."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"e152","DOI":"10.1563\/AAID-JOI-D-13-00225","article-title":"Importance of Poly(lactic-co-glycolic acid) in Scaffolds for Guided Bone Regeneration: A Focused Review","volume":"41","year":"2015","journal-title":"J. Oral Implantol."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"5240","DOI":"10.1021\/acsami.7b17620","article-title":"Tissue-Engineered Bone Immobilized with Human Adipose Stem Cells-Derived Exosomes Promotes Bone Regeneration","volume":"10","author":"Li","year":"2018","journal-title":"ACS Appl. Mater. Interfaces"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/13\/4385\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:03:40Z","timestamp":1760126620000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/13\/4385"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,29]]},"references-count":167,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["jcm12134385"],"URL":"https:\/\/doi.org\/10.3390\/jcm12134385","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,29]]}}}