{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T17:16:55Z","timestamp":1792689415791,"version":"4.5.0"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,12,21]],"date-time":"2024-12-21T00:00:00Z","timestamp":1734739200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2024,12,21]],"date-time":"2024-12-21T00:00:00Z","timestamp":1734739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2021QH011"],"award-info":[{"award-number":["ZR2021QH011"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Stem Cell Res Ther"],"DOI":"10.1186\/s13287-024-04111-6","type":"journal-article","created":{"date-parts":[[2024,12,21]],"date-time":"2024-12-21T16:10:34Z","timestamp":1734797434000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Exosomes derived from hypoxic mesenchymal stem cells restore ovarian function by enhancing angiogenesis"],"prefix":"10.1186","volume":"15","author":[{"given":"Qingxi","family":"Qu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2637-0408","authenticated-orcid":false,"given":"Linghong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Limei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqian","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunxiao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuanxuan","family":"Jing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxuan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,12,21]]},"reference":[{"key":"4111_CR1","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1089\/scd.2021.0005","volume":"30","author":"Y Zhou","year":"2021","unstructured":"Zhou Y, Zhou J, Xu X, Du F, Nie M, Hu L, Ma Y, Liu M, Yu S, Zhang J, Chen Y. Matrigel\/Umbilical Cord-Derived Mesenchymal Stem Cells Promote Granulosa Cell Proliferation and Ovarian Vascularization in a Mouse Model of Premature Ovarian Failure. Stem Cells Dev. 2021;30:782\u201396.","journal-title":"Stem Cells Dev"},{"key":"4111_CR2","doi-asserted-by":"publisher","first-page":"2333","DOI":"10.2217\/fon-2016-0176","volume":"12","author":"G Bedoschi","year":"2016","unstructured":"Bedoschi G, Navarro PA, Oktay K. Chemotherapy-induced damage to ovary: mechanisms and clinical impact. Future Oncol. 2016;12:2333\u201344.","journal-title":"Future Oncol"},{"key":"4111_CR3","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1089\/ten.teb.2020.0205","volume":"28","author":"MY Wang","year":"2022","unstructured":"Wang MY, Wang YX, Li-Ling J, Xie HQ. Adult Stem Cell Therapy for Premature Ovarian Failure: From Bench to Bedside. Tissue Eng Part B Rev. 2022;28:63\u201378.","journal-title":"Tissue Eng Part B Rev"},{"key":"4111_CR4","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1186\/s13287-021-02212-0","volume":"12","author":"YX Fu","year":"2021","unstructured":"Fu YX, Ji J, Shan F, Li J, Hu R. Human mesenchymal stem cell treatment of premature ovarian failure: new challenges and opportunities. Stem Cell Res Ther. 2021;12:161.","journal-title":"Stem Cell Res Ther"},{"key":"4111_CR5","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1186\/s13287-018-1008-9","volume":"9","author":"Y He","year":"2018","unstructured":"He Y, Chen D, Yang L, Hou Q, Ma H, Xu X. The therapeutic potential of bone marrow mesenchymal stem cells in premature ovarian failure. Stem Cell Res Ther. 2018;9:263.","journal-title":"Stem Cell Res Ther"},{"key":"4111_CR6","doi-asserted-by":"publisher","first-page":"576","DOI":"10.3109\/14653249.2010.507330","volume":"12","author":"DJ Prockop","year":"2010","unstructured":"Prockop DJ, Brenner M, Fibbe WE, Horwitz E, Blanc KL, Phinney DG, Simmons PJ, Sensebe L, Keating A. Defining the risks of mesenchymal stromal cell therapy. Cytotherapy. 2010;12:576\u20138.","journal-title":"Cytotherapy"},{"key":"4111_CR7","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1186\/s12967-020-02622-3","volume":"18","author":"S Nikfarjam","year":"2020","unstructured":"Nikfarjam S, Rezaie J, Zolbanin NM, Jafari R. Mesenchymal stem cell derived-exosomes: a modern approach in translational medicine. J Transl Med. 2020;18:449.","journal-title":"J Transl Med"},{"key":"4111_CR8","doi-asserted-by":"publisher","first-page":"814","DOI":"10.4252\/wjsc.v12.i8.814","volume":"12","author":"ZJ Ma","year":"2020","unstructured":"Ma ZJ, Yang JJ, Lu YB, Liu ZY, Wang XX. Mesenchymal stem cell-derived exosomes: Toward cell-free therapeutic strategies in regenerative medicine. World J Stem Cells. 2020;12:814\u201340.","journal-title":"World J Stem Cells"},{"key":"4111_CR9","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1186\/s13287-022-03056-y","volume":"13","author":"Q Qu","year":"2022","unstructured":"Qu Q, Liu L, Cui Y, Liu H, Yi J, Bing W, Liu C, Jiang D, Bi Y. miR-126-3p containing exosomes derived from human umbilical cord mesenchymal stem cells promote angiogenesis and attenuate ovarian granulosa cell apoptosis in a preclinical rat model of premature ovarian failure. Stem Cell Res Ther. 2022;13:352.","journal-title":"Stem Cell Res Ther"},{"key":"4111_CR10","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1177\/1947601911423654","volume":"2","author":"BL Krock","year":"2011","unstructured":"Krock BL, Skuli N, Simon MC. Hypoxia-induced angiogenesis: good and evil. Genes Cancer. 2011;2:1117\u201333.","journal-title":"Genes Cancer"},{"key":"4111_CR11","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1089\/ten.teb.2021.0145","volume":"28","author":"Y Yang","year":"2022","unstructured":"Yang Y, Lee EH, Yang Z. Hypoxia-Conditioned Mesenchymal Stem Cells in Tissue Regeneration Application. Tissue Eng Part B Rev. 2022;28:966\u201377.","journal-title":"Tissue Eng Part B Rev"},{"key":"4111_CR12","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1530\/REP-09-0283","volume":"138","author":"RS Robinson","year":"2009","unstructured":"Robinson RS, Woad KJ, Hammond AJ, Laird M, Hunter MG, GE Mann. Angiogenesis and vascular function in the ovary. Reproduction. 2009;138:869\u201381.","journal-title":"Reproduction"},{"key":"4111_CR13","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1111\/j.1439-0531.2004.00505.x","volume":"39","author":"C Tamanini","year":"2004","unstructured":"Tamanini C, De Ambrogi M. Angiogenesis in developing follicle and corpus luteum. Reprod Domest Anim. 2004;39:206\u201316.","journal-title":"Reprod Domest Anim"},{"key":"4111_CR14","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1186\/s13287-020-01639-1","volume":"11","author":"Q Qu","year":"2020","unstructured":"Qu Q, Pang Y, Zhang C, Liu L, Bi Y. Exosomes derived from human umbilical cord mesenchymal stem cells inhibit vein graft intimal hyperplasia and accelerate reendothelialization by enhancing endothelial function. Stem Cell Res Ther. 2020;11:133.","journal-title":"Stem Cell Res Ther"},{"key":"4111_CR15","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1186\/s13287-020-01978-z","volume":"11","author":"Q Qu","year":"2020","unstructured":"Qu Q, Wang L, Bing W, Bi Y, Zhang C, Jing X, Liu L. miRNA-126-3p carried by human umbilical cord mesenchymal stem cell enhances endothelial function through exosome-mediated mechanisms in vitro and attenuates vein graft neointimal formation in vivo. Stem Cell Res Ther. 2020;11:464.","journal-title":"Stem Cell Res Ther"},{"key":"4111_CR16","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1530\/JOE-10-0357","volume":"209","author":"T Sakurai","year":"2011","unstructured":"Sakurai T, Suzuki K, Yoshie M, Hashimoto K, Tachikawa E, Tamura K. Stimulation of tube formation mediated through the prostaglandin EP2 receptor in rat luteal endothelial cells. J Endocrinol. 2011;209:33\u201343.","journal-title":"J Endocrinol"},{"key":"4111_CR17","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1369\/jhc.4A6514.2005","volume":"54","author":"MP Pusztaszeri","year":"2006","unstructured":"Pusztaszeri MP, Seelentag W, Bosman FT. Immunohistochemical expression of endothelial markers CD31, CD34, von Willebrand factor, and Fli-1 in normal human tissues. J Histochem Cytochemistry. 2006;54:385\u201395.","journal-title":"J Histochem Cytochemistry"},{"key":"4111_CR18","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1111\/jcmm.12795","volume":"20","author":"W Bing","year":"2016","unstructured":"Bing W, Pang X, Qu Q, Bai X, Yang W, Bi Y, Bi X. Simvastatin improves the homing of BMSCs via the PI3K\/AKT\/miR-9 pathway. J Cell Mol Med. 2016;20:949\u201361.","journal-title":"J Cell Mol Med"},{"key":"4111_CR19","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/j.actbio.2022.07.015","volume":"150","author":"Y Zhuang","year":"2022","unstructured":"Zhuang Y, Cheng M, Li M, Cui J, Huang J, Zhang C, Si J, Lin K, Yu H. Small extracellular vesicles derived from hypoxic mesenchymal stem cells promote vascularized bone regeneration through the miR-210-3p\/EFNA3\/PI3K pathway. Acta Biomater. 2022;150:413\u201326.","journal-title":"Acta Biomater"},{"key":"4111_CR20","doi-asserted-by":"crossref","unstructured":"Kalluri R, LeBleu VS. The biology, function,biomedical applications of exosomes. Science. 2020;367:6977.","DOI":"10.1126\/science.aau6977"},{"key":"4111_CR21","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1038\/nri855","volume":"2","author":"C Thery","year":"2002","unstructured":"Thery C, Zitvogel L, Amigorena S. Exosomes: composition, biogenesis and function. Nat Rev Immunol. 2002;2:569\u201379.","journal-title":"Nat Rev Immunol"},{"key":"4111_CR22","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/s41556-018-0250-9","volume":"21","author":"M Mathieu","year":"2019","unstructured":"Mathieu M, Martin-Jaular L, Lavieu G, Thery C. Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication. Nat Cell Biol. 2019;21:9\u201317.","journal-title":"Nat Cell Biol"},{"key":"4111_CR23","doi-asserted-by":"crossref","unstructured":"Chen S, Sun F, Qian H, Xu W, Jiang J. (2022). Preconditioning and Engineering Strategies for Improving the Efficacy of Mesenchymal Stem Cell-Derived Exosomes in Cell-Free Therapy. Stem Cells Int 2022:1779346.","DOI":"10.1155\/2022\/1779346"},{"key":"4111_CR24","doi-asserted-by":"publisher","first-page":"4622","DOI":"10.1073\/pnas.081063798","volume":"98","author":"S Wen","year":"2001","unstructured":"Wen S, Stolarov J, Myers MP, Su JD, Wigler MH, Tonks NK, DL Durden. PTEN controls tumor-induced angiogenesis. Proc Natl Acad Sci U S A. 2001;98:4622\u20137.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"4111_CR25","doi-asserted-by":"publisher","first-page":"2054","DOI":"10.1101\/gad.1308805","volume":"19","author":"K Hamada","year":"2005","unstructured":"Hamada K, Sasaki T, Koni PA, Natsui M, Kishimoto H, Sasaki J, Yajima N, Horie Y, Hasegawa G, Naito M, Miyazaki J, Suda T, Itoh H, Nakao K, Mak TW, Nakano T, Suzuki A. The PTEN\/PI3K pathway governs normal vascular development and tumor angiogenesis. Genes Dev. 2005;19:2054\u201365.","journal-title":"Genes Dev"},{"key":"4111_CR26","doi-asserted-by":"publisher","first-page":"51","DOI":"10.3389\/fnmol.2011.00051","volume":"4","author":"J Karar","year":"2011","unstructured":"Karar J, Maity A. PI3K\/AKT\/mTOR Pathway in Angiogenesis. Front Mol Neurosci. 2011;4:51.","journal-title":"Front Mol Neurosci"},{"key":"4111_CR27","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/S0065-230X(09)02002-8","volume":"102","author":"BH Jiang","year":"2009","unstructured":"Jiang BH, Liu LZ. PI3K\/PTEN signaling in angiogenesis and tumorigenesis. Adv Cancer Res. 2009;102:19\u201365.","journal-title":"Adv Cancer Res"},{"key":"4111_CR28","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1093\/humupd\/dms022","volume":"18","author":"S Morgan","year":"2012","unstructured":"Morgan S, Anderson RA, Gourley C, Wallace WH, Spears N. How do chemotherapeutic agents damage the ovary? Hum Reprod Update. 2012;18:525\u201335.","journal-title":"Hum Reprod Update"},{"key":"4111_CR29","doi-asserted-by":"publisher","first-page":"1428","DOI":"10.1111\/jcmm.14822","volume":"24","author":"M Oltra","year":"2020","unstructured":"Oltra M, Vidal-Gil L, Maisto R, J Sancho\u2010Pelluz and, Barcia JM. Oxidative stress\u2010induced angiogenesis is mediated by miR\u2010205\u20105p. J Cell Mol Med. 2020;24:1428\u201336.","journal-title":"J Cell Mol Med"},{"key":"4111_CR30","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s13287-021-02694-y","volume":"13","author":"LT Nguyen","year":"2022","unstructured":"Nguyen LT, Tran NT, Than UTT, Nguyen MQ, Tran AM, Do PTX, Chu TT, Nguyen TD, Bui AV, Ngo TA, Hoang VT, NTM Hoang. Optimization of human umbilical cord blood-derived mesenchymal stem cell isolation and culture methods in serum- and xeno-free conditions. Stem Cell Res Ther. 2022;13:15.","journal-title":"Stem Cell Res Ther"},{"key":"4111_CR31","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1038\/cdd.2011.172","volume":"19","author":"JC Estrada","year":"2012","unstructured":"Estrada JC, Albo C, Benguria A, Dopazo A, Lopez-Romero P, Carrera-Quintanar L, Roche E, Clemente EP, Enriquez JA, Bernad A, Samper E. Culture of human mesenchymal stem cells at low oxygen tension improves growth and genetic stability by activating glycolysis. Cell Death Differ. 2012;19:743\u201355.","journal-title":"Cell Death Differ"},{"key":"4111_CR32","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1089\/ten.teb.2009.0296","volume":"16","author":"R Das","year":"2010","unstructured":"Das R, Jahr H, van Osch GJ, Farrell E. The role of hypoxia in bone marrow-derived mesenchymal stem cells: considerations for regenerative medicine approaches. Tissue Eng Part B Rev. 2010;16:159\u201368.","journal-title":"Tissue Eng Part B Rev"},{"key":"4111_CR33","doi-asserted-by":"crossref","unstructured":"Wang X, Tang Y, Liu Z, Yin Y, Li Q, Liu G, Yan B. (2021). The Application Potential and Advance of Mesenchymal Stem Cell-Derived Exosomes in Myocardial Infarction. Stem Cells Int 2021:5579904.","DOI":"10.1155\/2021\/5579904"},{"key":"4111_CR34","doi-asserted-by":"publisher","first-page":"1803","DOI":"10.1039\/D1BM01722E","volume":"10","author":"J Mu","year":"2022","unstructured":"Mu J, Li L, Wu J, Huang T, Zhang Y, Cao J, Ma T, Chen J, Zhang C, Zhang X, Lu T, Kong X, Sun J, Gao J. Hypoxia-stimulated mesenchymal stem cell-derived exosomes loaded by adhesive hydrogel for effective angiogenic treatment of spinal cord injury. Biomater Sci. 2022;10:1803\u201311.","journal-title":"Biomater Sci"},{"key":"4111_CR35","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1186\/s12951-021-00942-0","volume":"19","author":"J Wang","year":"2021","unstructured":"Wang J, Wu H, Peng Y, Zhao Y, Qin Y, Zhang Y, Xiao Z. Hypoxia adipose stem cell-derived exosomes promote high-quality healing of diabetic wound involves activation of PI3K\/Akt pathways. J Nanobiotechnol. 2021;19:202.","journal-title":"J Nanobiotechnol"}],"container-title":["Stem Cell Research & Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13287-024-04111-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13287-024-04111-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13287-024-04111-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,21]],"date-time":"2024-12-21T17:04:06Z","timestamp":1734800646000},"score":1,"resource":{"primary":{"URL":"https:\/\/stemcellres.biomedcentral.com\/articles\/10.1186\/s13287-024-04111-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,21]]},"references-count":35,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["4111"],"URL":"https:\/\/doi.org\/10.1186\/s13287-024-04111-6","relation":{},"ISSN":["1757-6512"],"issn-type":[{"value":"1757-6512","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,21]]},"assertion":[{"value":"10 May 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 December 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 December 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The experimental procedures associated with human cells and animals were approved. (1) Title of the approved project: The effect of human umbilical cord-derived mesenchymal stem cell and its exosomes in premature ovarian failure; (2) Name of the institutional approval committee or unit: Ethics Committee of Qilu Hospital of Shandong University; (3) Approval number: KYLL-202203-013; (4) Date of approval: 18 March 2022.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors read and approved the final manuscript.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"496"}}