{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:40:51Z","timestamp":1787020851360,"version":"build-2736575974"},"reference-count":49,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T00:00:00Z","timestamp":1626307200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T00:00:00Z","timestamp":1626307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81771561"],"award-info":[{"award-number":["81771561"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81830043"],"award-info":[{"award-number":["81830043"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81801427"],"award-info":[{"award-number":["81801427"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005089","name":"Beijing Municipal Natural Science Foundation","doi-asserted-by":"publisher","award":["7192154"],"award-info":[{"award-number":["7192154"]}],"id":[{"id":"10.13039\/501100005089","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Chinese Academy of Medical Sciences innovation project","award":["No. 2017-I2M-1-002"],"award-info":[{"award-number":["No. 2017-I2M-1-002"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Stem Cell Res Ther"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Current surgical therapies for pelvic organ prolapse (POP) do not repair weak vaginal tissue and just provide support; these therapies may trigger severe complications. Stem cell-based regenerative therapy, due to its ability to reconstruct damaged tissue, may be a promising therapeutic strategy for POP. The objective of this study is to evaluate whether mesenchymal stem cell (MSC) therapy can repair weak vaginal tissue in an ovariectomized rhesus macaque model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A bilateral ovariectomy model was established in rhesus macaques to induce menopause-related vaginal injury. Ten bilaterally ovariectomized rhesus macaques were divided into two groups (n=5\/group): the saline group and the MSC group. Three months after ovariectomy, saline or MSCs were injected in situ into the injured vaginal wall. The vaginal tissue was harvested 12 weeks after injection for histological and biochemical analyses to evaluate changes of extracellular matrix, microvascular density, and smooth muscle in the vaginal tissue. Biomechanical properties of the vaginal tissue were assessed by uniaxial tensile testing. Data analysis was performed with unpaired Student\u2019s t test or Mann-Whitney.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Twelve weeks after MSC transplantation, histological and biochemical analyses revealed that the content of collagen I, elastin, and microvascular density in the lamina propria of the vagina increased significantly in the MSC group compared with the saline group. And the fraction of smooth muscle in the muscularis of vagina increased significantly in the MSC group. In addition, MSC transplantation improved the biomechanical properties of the vagina by enhancing the elastic modulus.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Vaginal MSC transplantation could repair the weak vaginal tissue by promoting extracellular matrix ingrowth, neovascularization, and smooth muscle formation and improve the biomechanical properties of the vagina, providing a new prospective treatment for POP.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13287-021-02488-2","type":"journal-article","created":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T07:02:58Z","timestamp":1626332578000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Mesenchymal stem cell transplantation for vaginal repair in an ovariectomized rhesus macaque model"],"prefix":"10.1186","volume":"12","author":[{"given":"Ye","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yidi","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xudong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqian","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,15]]},"reference":[{"issue":"1","key":"2488_CR1","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1007\/s00192-009-0976-9","volume":"21","author":"BT Haylen","year":"2010","unstructured":"Haylen BT, de Ridder D, Freeman RM, Swift SE, Berghmans B, Lee J, et al. An International Urogynecological Association (IUGA)\/International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction. Int Urogynecol J. 2010;21(1):5\u201326. https:\/\/doi.org\/10.1007\/s00192-009-0976-9.","journal-title":"Int Urogynecol J"},{"issue":"11","key":"2488_CR2","doi-asserted-by":"publisher","first-page":"1925","DOI":"10.1007\/s00192-018-03859-9","volume":"30","author":"Z Li","year":"2019","unstructured":"Li Z, Xu T, Li Z, Gong J, Liu Q, Zhu L. An epidemiologic study of pelvic organ prolapse in rural Chinese women: a population-based sample in China. Int Urogynecol J. 2019;30(11):1925\u201332. https:\/\/doi.org\/10.1007\/s00192-018-03859-9.","journal-title":"Int Urogynecol J"},{"issue":"2","key":"2488_CR3","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/S0002-9378(99)70203-6","volume":"180","author":"EC Samuelsson","year":"1999","unstructured":"Samuelsson EC, Victor FT, Tibblin G, Sv\u00e4rdsudd KF. Signs of genital prolapse in a Swedish population of women 20 to 59 years of age and possible related factors. Am J Obstet Gynecol. 1999;180(2):299\u2013305. https:\/\/doi.org\/10.1016\/S0002-9378(99)70203-6.","journal-title":"Am J Obstet Gynecol"},{"issue":"3","key":"2488_CR4","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1007\/s00192-007-0459-9","volume":"19","author":"MF Fialkow","year":"2008","unstructured":"Fialkow MF, Newton KM, Lentz GM, Weiss NS. Lifetime risk of surgical management for pelvic organ prolapse or urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct. 2008;19(3):437\u201340. https:\/\/doi.org\/10.1007\/s00192-007-0459-9.","journal-title":"Int Urogynecol J Pelvic Floor Dysfunct"},{"issue":"5","key":"2488_CR5","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1097\/AOG.0b013e3181f73729","volume":"116","author":"FJ Smith","year":"2010","unstructured":"Smith FJ, Holman CD, Moorin RE, Tsokos N. Lifetime risk of undergoing surgery for pelvic organ prolapse. Obstet Gynecol. 2010;116(5):1096\u2013100. https:\/\/doi.org\/10.1097\/AOG.0b013e3181f73729.","journal-title":"Obstet Gynecol"},{"issue":"4","key":"2488_CR6","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1016\/s0029-7844(01)01472-7","volume":"98","author":"LL Subak","year":"2001","unstructured":"Subak LL, Waetjen LE, van den Eeden S, Thom DH, Vittinghoff E, Brown JS. Cost of pelvic organ prolapse surgery in the United States. Obstet Gynecol. 2001;98(4):646\u201351. https:\/\/doi.org\/10.1016\/s0029-7844(01)01472-7.","journal-title":"Obstet Gynecol"},{"issue":"1","key":"2488_CR7","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1007\/s00192-011-1584-z","volume":"23","author":"EJ Stanford","year":"2012","unstructured":"Stanford EJ, Cassidenti A, Moen MD. Traditional native tissue versus mesh-augmented pelvic organ prolapse repairs: providing an accurate interpretation of current literature. Int Urogynecol J. 2012;23(1):19\u201328. https:\/\/doi.org\/10.1007\/s00192-011-1584-z.","journal-title":"Int Urogynecol J"},{"key":"2488_CR8","doi-asserted-by":"crossref","unstructured":"Maher C, Feiner B, Baessler K, Schmid C. Surgical management of pelvic organ prolapse in women. Cochrane Database Syst Rev. 2013;Cd004014.","DOI":"10.1002\/14651858.CD004014.pub5"},{"issue":"9566","key":"2488_CR9","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.1016\/S0140-6736(07)60462-0","volume":"369","author":"JE Jelovsek","year":"2007","unstructured":"Jelovsek JE, Maher C, Barber MD. Pelvic organ prolapse. Lancet. 2007;369(9566):1027\u201338. https:\/\/doi.org\/10.1016\/S0140-6736(07)60462-0.","journal-title":"Lancet."},{"key":"2488_CR10","doi-asserted-by":"publisher","first-page":"590.e1-6","DOI":"10.1016\/j.ajog.2008.02.022","volume":"198","author":"DD Rahn","year":"2008","unstructured":"Rahn DD, Ruff MD, Brown SA, Tibbals HF, Word RA. Biomechanical properties of the vaginal wall: effect of pregnancy, elastic fiber deficiency, and pelvic organ prolapse. Am J Obstet Gynecol. 2008;198:590.e1-6.","journal-title":"Am J Obstet Gynecol"},{"key":"2488_CR11","doi-asserted-by":"publisher","first-page":"165.e1-6","DOI":"10.1016\/j.ajog.2007.03.040","volume":"197","author":"LB Epstein","year":"2007","unstructured":"Epstein LB, Graham CA, Heit MH. Systemic and vaginal biomechanical properties of women with normal vaginal support and pelvic organ prolapse. Am J Obstet Gynecol. 2007;197:165.e1-6.","journal-title":"Am J Obstet Gynecol"},{"issue":"7","key":"2488_CR12","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1016\/j.scib.2019.02.007","volume":"64","author":"L Li","year":"2019","unstructured":"Li L, Kang J, Zhang Y, Mao M, Yang Y, Lang J, et al. LAMC1, LAMA2 and LAMA3 gene polymorphisms and the risk for severe pelvic organ prolapse. Sci Bull. 2019;64(7):466\u20138. https:\/\/doi.org\/10.1016\/j.scib.2019.02.007.","journal-title":"Sci Bull"},{"key":"2488_CR13","doi-asserted-by":"publisher","first-page":"2604","DOI":"10.4081\/ejh.2016.2604","volume":"60","author":"A Vetuschi","year":"2016","unstructured":"Vetuschi A, D'Alfonso A, Sferra R, Zanelli D, Pompili S, Patacchiola F, et al. Changes in muscularis propria of anterior vaginal wall in women with pelvic organ prolapse. Eur J Histochem. 2016;60:2604.","journal-title":"Eur J Histochem"},{"issue":"3","key":"2488_CR14","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1016\/j.juro.2012.05.017","volume":"188","author":"L Zhou","year":"2012","unstructured":"Zhou L, Lee JH, Wen Y, Constantinou C, Yoshinobu M, Omata S, et al. Biomechanical properties and associated collagen composition in vaginal tissue of women with pelvic organ prolapse. J Urol. 2012;188(3):875\u201380. https:\/\/doi.org\/10.1016\/j.juro.2012.05.017.","journal-title":"J Urol"},{"issue":"5, Part 1","key":"2488_CR15","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1097\/01.AOG.0000182584.15087.dd","volume":"106","author":"PA Moalli","year":"2005","unstructured":"Moalli PA, Shand SH, Zyczynski HM, Gordy SC, Meyn LA. Remodeling of vaginal connective tissue in patients with prolapse. Obstet Gynecol. 2005;106(5, Part 1):953\u201363. https:\/\/doi.org\/10.1097\/01.AOG.0000182584.15087.dd.","journal-title":"Obstet Gynecol"},{"issue":"3","key":"2488_CR16","doi-asserted-by":"publisher","first-page":"307","DOI":"10.2217\/rme.10.37","volume":"5","author":"C Mason","year":"2010","unstructured":"Mason C, Manzotti E. Regenerative medicine cell therapies: numbers of units manufactured and patients treated between 1988 and 2010. Regen Med. 2010;5(3):307\u201313. https:\/\/doi.org\/10.2217\/rme.10.37.","journal-title":"Regen Med"},{"key":"2488_CR17","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1016\/j.actbio.2014.10.043","volume":"13","author":"SL Edwards","year":"2015","unstructured":"Edwards SL, Ulrich D, White JF, Su K, Rosamilia A, Ramshaw JA, et al. Temporal changes in the biomechanical properties of endometrial mesenchymal stem cell seeded scaffolds in a rat model. Acta Biomater. 2015;13:286\u201394. https:\/\/doi.org\/10.1016\/j.actbio.2014.10.043.","journal-title":"Acta Biomater"},{"key":"2488_CR18","doi-asserted-by":"publisher","first-page":"119495","DOI":"10.1016\/j.biomaterials.2019.119495","volume":"225","author":"S Emmerson","year":"2019","unstructured":"Emmerson S, Mukherjee S, Melendez-Munoz J, Cousins F, Edwards SL, Karjalainen P, et al. Composite mesh design for delivery of autologous mesenchymal stem cells influences mesh integration, exposure and biocompatibility in an ovine model of pelvic organ prolapse. Biomaterials. 2019;225:119495. https:\/\/doi.org\/10.1016\/j.biomaterials.2019.119495.","journal-title":"Biomaterials."},{"issue":"4","key":"2488_CR19","doi-asserted-by":"publisher","first-page":"20180089","DOI":"10.1098\/rsfs.2018.0089","volume":"9","author":"S Mukherjee","year":"2019","unstructured":"Mukherjee S, Darzi S, Paul K, Werkmeister JA, Gargett CE. Mesenchymal stem cell-based bioengineered constructs: foreign body response, cross-talk with macrophages and impact of biomaterial design strategies for pelvic floor disorders. Interface Focus. 2019;9(4):20180089. https:\/\/doi.org\/10.1098\/rsfs.2018.0089.","journal-title":"Interface Focus"},{"key":"2488_CR20","doi-asserted-by":"publisher","unstructured":"Beeravolu N, McKee C, Alamri A, Mikhael S, Brown C, Perez-Cruet M, et al. Isolation and characterization of mesenchymal stromal cells from human umbilical cord and fetal placenta. J Vis Exp. 2017;(122). https:\/\/doi.org\/10.3791\/55224.","DOI":"10.3791\/55224"},{"key":"2488_CR21","first-page":"8921284","volume":"2019","author":"M Mao","year":"2019","unstructured":"Mao M, Li Y, Zhang Y, Kang J, Zhu L. Tissue composition and biomechanical property changes in the vaginal wall of ovariectomized young rats. Biomed Res Int. 2019;2019:8921284.","journal-title":"Biomed Res Int"},{"issue":"12","key":"2488_CR22","doi-asserted-by":"publisher","first-page":"2011","DOI":"10.1007\/s00192-013-2111-1","volume":"24","author":"L De Landsheere","year":"2013","unstructured":"De Landsheere L, Munaut C, Nusgens B, Maillard C, Rubod C, Nisolle M, et al. Histology of the vaginal wall in women with pelvic organ prolapse: a literature review. Int Urogynecol J. 2013;24(12):2011\u201320. https:\/\/doi.org\/10.1007\/s00192-013-2111-1.","journal-title":"Int Urogynecol J"},{"key":"2488_CR23","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.ejogrb.2019.01.012","volume":"234","author":"R Gong","year":"2019","unstructured":"Gong R, Xia Z. Collagen changes in pelvic support tissues in women with pelvic organ prolapse. Eur J Obstet Gynecol Reprod Biol. 2019;234:185\u20139. https:\/\/doi.org\/10.1016\/j.ejogrb.2019.01.012.","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"issue":"3","key":"2488_CR24","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1007\/s00192-011-1532-y","volume":"23","author":"K Lammers","year":"2012","unstructured":"Lammers K, Lince SL, Spath MA, van Kempen LC, Hendriks JC, Vierhout ME, et al. Pelvic organ prolapse and collagen-associated disorders. Int Urogynecol J. 2012;23(3):313\u20139. https:\/\/doi.org\/10.1007\/s00192-011-1532-y.","journal-title":"Int Urogynecol J"},{"issue":"4","key":"2488_CR25","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1007\/s00192-008-0737-1","volume":"20","author":"MH Kerkhof","year":"2009","unstructured":"Kerkhof MH, Hendriks L, Br\u00f6lmann HA. Changes in connective tissue in patients with pelvic organ prolapse--a review of the current literature. Int Urogynecol J Pelvic Floor Dysfunct. 2009;20(4):461\u201374. https:\/\/doi.org\/10.1007\/s00192-008-0737-1.","journal-title":"Int Urogynecol J Pelvic Floor Dysfunct"},{"issue":"9","key":"2488_CR26","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1369\/0022155418772798","volume":"66","author":"A Vetuschi","year":"2018","unstructured":"Vetuschi A, Pompili S, Gallone A, D'Alfonso A, Carbone MG, Carta G, et al. Immunolocalization of advanced glycation end products, mitogen activated protein kinases, and transforming growth factor-\u03b2\/Smads in pelvic organ prolapse. J Histochem Cytochem. 2018;66(9):673\u201386. https:\/\/doi.org\/10.1369\/0022155418772798.","journal-title":"J Histochem Cytochem"},{"issue":"1","key":"2488_CR27","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1007\/s00423-003-0429-8","volume":"389","author":"K Junge","year":"2004","unstructured":"Junge K, Klinge U, Rosch R, Mertens PR, Kirch J, Klosterhalfen B, et al. Decreased collagen type I\/III ratio in patients with recurring hernia after implantation of alloplastic prostheses. Langenbeck's Arch Surg. 2004;389(1):17\u201322. https:\/\/doi.org\/10.1007\/s00423-003-0429-8.","journal-title":"Langenbeck's Arch Surg"},{"issue":"6868","key":"2488_CR28","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1038\/415168a","volume":"415","author":"H Yanagisawa","year":"2002","unstructured":"Yanagisawa H, Davis EC, Starcher BC, Ouchi T, Yanagisawa M, Richardson JA, et al. Fibulin-5 is an elastin-binding protein essential for elastic fibre development in vivo. Nature. 2002;415(6868):168\u201371. https:\/\/doi.org\/10.1038\/415168a.","journal-title":"Nature."},{"issue":"2","key":"2488_CR29","doi-asserted-by":"publisher","first-page":"578","DOI":"10.2353\/ajpath.2007.060662","volume":"170","author":"PG Drewes","year":"2007","unstructured":"Drewes PG, Yanagisawa H, Starcher B, Hornstra I, Csiszar K, Marinis SI, et al. Pelvic organ prolapse in fibulin-5 knockout mice: pregnancy-induced changes in elastic fiber homeostasis in mouse vagina. Am J Pathol. 2007;170(2):578\u201389. https:\/\/doi.org\/10.2353\/ajpath.2007.060662.","journal-title":"Am J Pathol"},{"issue":"4","key":"2488_CR30","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0152793","volume":"11","author":"K Chin","year":"2016","unstructured":"Chin K, Wieslander C, Shi H, Balgobin S, Montoya TI, Yanagisawa H, et al. Pelvic organ support in animals with partial loss of fibulin-5 in the vaginal wall. PLoS One. 2016;11(4):e0152793. https:\/\/doi.org\/10.1371\/journal.pone.0152793.","journal-title":"PLoS One"},{"issue":"1","key":"2488_CR31","doi-asserted-by":"publisher","first-page":"88","DOI":"10.3109\/14653240903350265","volume":"12","author":"G Lin","year":"2010","unstructured":"Lin G, Wang G, Banie L, Ning H, Shindel AW, Fandel TM, et al. Treatment of stress urinary incontinence with adipose tissue-derived stem cells. Cytotherapy. 2010;12(1):88\u201395. https:\/\/doi.org\/10.3109\/14653240903350265.","journal-title":"Cytotherapy."},{"issue":"6","key":"2488_CR32","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1177\/1933719113512529","volume":"21","author":"M Alarab","year":"2014","unstructured":"Alarab M, Kufaishi H, Lye S, Drutz H, Shynlova O. Expression of extracellular matrix-remodeling proteins is altered in vaginal tissue of premenopausal women with severe pelvic organ prolapse. Reprod Sci. 2014;21(6):704\u201315. https:\/\/doi.org\/10.1177\/1933719113512529.","journal-title":"Reprod Sci"},{"issue":"1","key":"2488_CR33","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.ejogrb.2010.12.043","volume":"156","author":"M Dviri","year":"2011","unstructured":"Dviri M, Leron E, Dreiher J, Mazor M, Shaco-Levy R. Increased matrix metalloproteinases-1,-9 in the uterosacral ligaments and vaginal tissue from women with pelvic organ prolapse. Eur J Obstet Gynecol Reprod Biol. 2011;156(1):113\u20137. https:\/\/doi.org\/10.1016\/j.ejogrb.2010.12.043.","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"issue":"3","key":"2488_CR34","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1016\/j.stem.2012.02.005","volume":"10","author":"SH Ranganath","year":"2012","unstructured":"Ranganath SH, Levy O, Inamdar MS, Karp JM. Harnessing the mesenchymal stem cell secretome for the treatment of cardiovascular disease. Cell Stem Cell. 2012;10(3):244\u201358. https:\/\/doi.org\/10.1016\/j.stem.2012.02.005.","journal-title":"Cell Stem Cell"},{"issue":"3","key":"2488_CR35","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1016\/j.cardiores.2005.12.002","volume":"69","author":"H Nagase","year":"2006","unstructured":"Nagase H, Visse R, Murphy G. Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc Res. 2006;69(3):562\u201373. https:\/\/doi.org\/10.1016\/j.cardiores.2005.12.002.","journal-title":"Cardiovasc Res"},{"issue":"12","key":"2488_CR36","doi-asserted-by":"publisher","first-page":"2189","DOI":"10.1089\/scd.2011.0674","volume":"21","author":"ST Hsiao","year":"2012","unstructured":"Hsiao ST, Asgari A, Lokmic Z, Sinclair R, Dusting GJ, Lim SY, et al. Comparative analysis of paracrine factor expression in human adult mesenchymal stem cells derived from bone marrow, adipose, and dermal tissue. Stem Cells Dev. 2012;21(12):2189\u2013203. https:\/\/doi.org\/10.1089\/scd.2011.0674.","journal-title":"Stem Cells Dev"},{"issue":"2","key":"2488_CR37","doi-asserted-by":"publisher","first-page":"103","DOI":"10.2174\/157488810791268564","volume":"5","author":"AJ Salgado","year":"2010","unstructured":"Salgado AJ, Reis RL, Sousa NJ, Gimble JM. Adipose tissue derived stem cells secretome: soluble factors and their roles in regenerative medicine. Curr Stem Cell Res Ther. 2010;5(2):103\u201310. https:\/\/doi.org\/10.2174\/157488810791268564.","journal-title":"Curr Stem Cell Res Ther"},{"key":"2488_CR38","first-page":"953.e1-8","volume":"80","author":"GY Li","year":"2012","unstructured":"Li GY, Zhou F, Gong YQ, Cui WS, Yuan YM, Song WD, et al. Activation of VEGF and ERK1\/2 and improvement of urethral function by adipose-derived stem cells in a rat stress urinary incontinence model. Urology. 2012;80:953.e1-8.","journal-title":"Urology"},{"issue":"3-4","key":"2488_CR39","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1089\/ten.TEA.2013.0170","volume":"20","author":"D Ulrich","year":"2014","unstructured":"Ulrich D, Edwards SL, Su K, Tan KS, White JF, Ramshaw JA, et al. Human endometrial mesenchymal stem cells modulate the tissue response and mechanical behavior of polyamide mesh implants for pelvic organ prolapse repair. Tissue Eng Part A. 2014;20(3-4):785\u201398. https:\/\/doi.org\/10.1089\/ten.TEA.2013.0170.","journal-title":"Tissue Eng Part A"},{"issue":"3","key":"2488_CR40","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1016\/j.bbrc.2007.09.058","volume":"363","author":"S Sadat","year":"2007","unstructured":"Sadat S, Gehmert S, Song YH, Yen Y, Bai X, Gaiser S, et al. The cardioprotective effect of mesenchymal stem cells is mediated by IGF-I and VEGF. Biochem Biophys Res Commun. 2007;363(3):674\u20139. https:\/\/doi.org\/10.1016\/j.bbrc.2007.09.058.","journal-title":"Biochem Biophys Res Commun"},{"issue":"5","key":"2488_CR41","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1097\/SPV.0b013e31829ff74d","volume":"19","author":"S Mei","year":"2013","unstructured":"Mei S, Ye M, Gil L, Zhang J, Zhang Y, Candiotti K, et al. The role of smooth muscle cells in the pathophysiology of pelvic organ prolapse. Female Pelvic Med Reconstr Surg. 2013;19(5):254\u20139. https:\/\/doi.org\/10.1097\/SPV.0b013e31829ff74d.","journal-title":"Female Pelvic Med Reconstr Surg"},{"issue":"1","key":"2488_CR42","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1067\/mob.2002.124843","volume":"187","author":"MK Boreham","year":"2002","unstructured":"Boreham MK, Wai CY, Miller RT, Schaffer JI, Word RA. Morphometric analysis of smooth muscle in the anterior vaginal wall of women with pelvic organ prolapse. Am J Obstet Gynecol. 2002;187(1):56\u201363. https:\/\/doi.org\/10.1067\/mob.2002.124843.","journal-title":"Am J Obstet Gynecol"},{"issue":"6","key":"2488_CR43","doi-asserted-by":"publisher","first-page":"1501","DOI":"10.1067\/mob.2002.130005","volume":"187","author":"MK Boreham","year":"2002","unstructured":"Boreham MK, Wai CY, Miller RT, Schaffer JI, Word RA. Morphometric properties of the posterior vaginal wall in women with pelvic organ prolapse. Am J Obstet Gynecol. 2002;187(6):1501\u20138; discussion 8-9. https:\/\/doi.org\/10.1067\/mob.2002.130005.","journal-title":"Am J Obstet Gynecol"},{"issue":"1","key":"2488_CR44","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.eururo.2010.10.038","volume":"59","author":"W Zhao","year":"2011","unstructured":"Zhao W, Zhang C, Jin C, Zhang Z, Kong D, Xu W, et al. Periurethral injection of autologous adipose-derived stem cells with controlled-release nerve growth factor for the treatment of stress urinary incontinence in a rat model. Eur Urol. 2011;59(1):155\u201363. https:\/\/doi.org\/10.1016\/j.eururo.2010.10.038.","journal-title":"Eur Urol"},{"issue":"3","key":"2488_CR45","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1002\/nau.20998","volume":"30","author":"J Corcos","year":"2011","unstructured":"Corcos J, Loutochin O, Campeau L, Eliopoulos N, Bouchentouf M, Blok B, et al. Bone marrow mesenchymal stromal cell therapy for external urethral sphincter restoration in a rat model of stress urinary incontinence. Neurourol Urodyn. 2011;30(3):447\u201355. https:\/\/doi.org\/10.1002\/nau.20998.","journal-title":"Neurourol Urodyn"},{"issue":"32","key":"2488_CR46","doi-asserted-by":"publisher","first-page":"12167","DOI":"10.1073\/pnas.0604850103","volume":"103","author":"LV Rodr\u00edguez","year":"2006","unstructured":"Rodr\u00edguez LV, Alfonso Z, Zhang R, Leung J, Wu B, Ignarro LJ. Clonogenic multipotent stem cells in human adipose tissue differentiate into functional smooth muscle cells. Proc Natl Acad Sci U S A. 2006;103(32):12167\u201372. https:\/\/doi.org\/10.1073\/pnas.0604850103.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"2488_CR47","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1016\/j.juro.2006.09.103","volume":"177","author":"P De Coppi","year":"2007","unstructured":"De Coppi P, Callegari A, Chiavegato A, Gasparotto L, Piccoli M, Taiani J, et al. Amniotic fluid and bone marrow derived mesenchymal stem cells can be converted to smooth muscle cells in the cryo-injured rat bladder and prevent compensatory hypertrophy of surviving smooth muscle cells. J Urol. 2007;177(1):369\u201376. https:\/\/doi.org\/10.1016\/j.juro.2006.09.103.","journal-title":"J Urol"},{"issue":"12","key":"2488_CR48","doi-asserted-by":"publisher","first-page":"1531","DOI":"10.1016\/j.addr.2003.08.002","volume":"55","author":"K Gelse","year":"2003","unstructured":"Gelse K, P\u00f6schl E, Aigner T. Collagens--structure, function, and biosynthesis. Adv Drug Deliv Rev. 2003;55(12):1531\u201346. https:\/\/doi.org\/10.1016\/j.addr.2003.08.002.","journal-title":"Adv Drug Deliv Rev"},{"issue":"18","key":"2488_CR49","doi-asserted-by":"publisher","first-page":"4872","DOI":"10.1016\/j.biomaterials.2010.02.056","volume":"31","author":"XH Zou","year":"2010","unstructured":"Zou XH, Zhi YL, Chen X, Jin HM, Wang LL, Jiang YZ, et al. Mesenchymal stem cell seeded knitted silk sling for the treatment of stress urinary incontinence. Biomaterials. 2010;31(18):4872\u20139. https:\/\/doi.org\/10.1016\/j.biomaterials.2010.02.056.","journal-title":"Biomaterials."}],"container-title":["Stem Cell Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13287-021-02488-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13287-021-02488-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13287-021-02488-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T07:23:40Z","timestamp":1626333820000},"score":1,"resource":{"primary":{"URL":"https:\/\/stemcellres.biomedcentral.com\/articles\/10.1186\/s13287-021-02488-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,15]]},"references-count":49,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["2488"],"URL":"https:\/\/doi.org\/10.1186\/s13287-021-02488-2","relation":{},"ISSN":["1757-6512"],"issn-type":[{"value":"1757-6512","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,15]]},"assertion":[{"value":"25 April 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 July 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 July 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All procedures were approved by the ethics committee of the Peking Union Medical College Hospital (JS-2043) and the ethics committee of the Beijing Institute of Xieerxin Biology Resource (E20190401). All institutional and national guidelines for the care and use of laboratory animals were followed.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"406"}}