{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T10:08:16Z","timestamp":1788343696482,"version":"build-2803163510"},"reference-count":21,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2023,1,11]],"date-time":"2023-01-11T00:00:00Z","timestamp":1673395200000},"content-version":"vor","delay-in-days":1080,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"},{"start":{"date-parts":[[2020,1,27]],"date-time":"2020-01-27T00:00:00Z","timestamp":1580083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,2,23]],"date-time":"2021-02-23T00:00:00Z","timestamp":1614038400000},"content-version":"am","delay-in-days":393,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100007485","name":"AFIRM II","doi-asserted-by":"publisher","award":["W81XWH-13-2-0052"],"award-info":[{"award-number":["W81XWH-13-2-0052"]}],"id":[{"id":"10.13039\/100007485","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007485","name":"Armed Forces Institute of Regenerative Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007485","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["jsm.jsexmed.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>The human placenta provides a bountiful and noncontroversial source of stem cells which have the potential for regeneration of injured tissue. These cells may restore erectile function after neurovascular tissue injury such as that seen in radical pelvic surgeries and pelvic trauma.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Aim<\/jats:title>\n                  <jats:p>To determine the effect of human placenta\u2013derived stem cells on erectile function recovery and histological changes at various time points in a cavernous nerve injury rat model and to study the fate of injected stem cells throughout the regenerative process.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Human placental stem cells (PSCs) were dual labeled with monomeric Katushka far red fluorescent protein (mKATE)-renLUC using a lentivirus vector. A pelvic neurovascular injury\u2013induced erectile dysfunction model was established in male, athymic rats by crushing the cavernous nerves and ligating the internal pudendal neurovascular bundles, bilaterally. At the time of defect creation, nonlabeled PSCs were injected into the corpus cavernosum at a concentration of 2.5 \u00d7 106 cells\/0.2 mL. The phosphate-buffered saline\u2013treated group served as the negative control group, and age-matched rats (age-matched controls) were used as the control group. Erectile function, histomorphological analyses, and Western blot were assessed at 1, 6, and 12 weeks after model creation. The distribution of implanted, dual-labeled PSCs was monitored using an in vivo imaging system (IVIS). Implanted cells were further tracked by detection of mKATE fluorescence in histological sections.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Main Outcome Measure<\/jats:title>\n                  <jats:p>The main outcome measure includes intracavernous pressure\/mean arterial pressure ratio, neural, endothelial, smooth muscle cell regeneration, mKATE fluorescence, and IVIS imaging.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The ratio of intracavernous pressure to mean arterial pressure significantly increased in PSC-injected rats compared with phosphate-buffered saline controls (P &amp;lt; 0.05) at the 6- and 12-week time points, reaching 72% and 68% of the age-matched control group, respectively. Immunofluorescence staining and Western blot analysis showed significant increases in markers of neurons (84.3%), endothelial cells (70.2%), and smooth muscle cells (70.3%) by 6 weeks in treatment groups compared with negative controls. These results were maintained through 12 weeks. IVIS analysis showed luminescence of implanted PSCs in the injected corpora immediately after injection and migration of cells to the sites of injury, including the incision site and periprostatic vasculature by day 1. mKATE fluorescence data revealed the presence of PSCs in the penile corpora and major pelvic ganglion at 1 and 3 days postoperatively. At 7 days, immunofluorescence of penile PSCs had disappeared and was diminished in the major pelvic ganglion.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical Implications<\/jats:title>\n                  <jats:p>Placenta-derived stem cells may represent a future \u201coff-the-shelf\u201d treatment to mitigate against development of erectile dysfunction after radical prostatectomy or other forms of pelvic injury.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Strength &amp; Limitations<\/jats:title>\n                  <jats:p>Single dose injection of PSCs after injury resulted in maximal functional recovery and tissue regeneration at 6 weeks, and the results were maintained through 12 weeks. Strategies to optimize adult stem cell therapy might achieve more effective outcomes for human clinical trials.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Human PSC therapy effectively restores the erectile tissue and function in this animal model. Thus, PSC therapy may provide an attractive modality to lessen the incidence of erectile dysfunction after pelvic neurovascular injury. Further improvement in tissue regeneration and functional recovery may be possible using multiple injections or systemic introduction of stem cells.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1016\/j.jsxm.2019.12.002","type":"journal-article","created":{"date-parts":[[2020,1,27]],"date-time":"2020-01-27T23:12:06Z","timestamp":1580166726000},"page":"400-411","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":19,"title":["Dynamic Changes in Erectile Function and Histological Architecture After Intracorporal Injection of Human Placental Stem Cells in a Pelvic Neurovascular Injury Rat Model"],"prefix":"10.1093","volume":"17","author":[{"given":"Xin","family":"Gu","sequence":"first","affiliation":[{"name":"Department of Urology , Shanghai, \u00a0 China"},{"name":"Shanghai Ninth People's Hospital , Shanghai, \u00a0 China"},{"name":"Shanghai JiaoTong University School of Medicine , Shanghai, \u00a0 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parth U.","family":"Thakker","sequence":"additional","affiliation":[{"name":"Wake Forest Institute for Regenerative Medicine , Winston-Salem, NC , USA"},{"name":"Wake Forest School of Medicine , Winston-Salem, NC , USA"},{"name":"Department of Urology , Winston-Salem, NC , USA"},{"name":"Wake Forest Baptist Medical Center , Winston-Salem, NC , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethan L.","family":"Matz","sequence":"additional","affiliation":[{"name":"Department of Urology , Winston-Salem, NC , USA"},{"name":"Wake Forest Baptist Medical Center , Winston-Salem, NC , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan P.","family":"Terlecki","sequence":"additional","affiliation":[{"name":"Department of Urology , Winston-Salem, NC , USA"},{"name":"Wake Forest Baptist Medical Center , Winston-Salem, NC , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank C.","family":"Marini","sequence":"additional","affiliation":[{"name":"Wake Forest Institute for Regenerative Medicine , Winston-Salem, NC , USA"},{"name":"Wake Forest School of Medicine , Winston-Salem, NC , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie G.","family":"Allickson","sequence":"additional","affiliation":[{"name":"Wake Forest Institute for Regenerative Medicine , Winston-Salem, NC , USA"},{"name":"Wake Forest School of Medicine , Winston-Salem, NC , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom F.","family":"Lue","sequence":"additional","affiliation":[{"name":"Department of Urology , San Francisco, CA , USA"},{"name":"University of California , San Francisco, CA , USA"},{"name":"San Francisco , San Francisco, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiting","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Urology , San Francisco, CA , USA"},{"name":"University of California , San Francisco, CA , USA"},{"name":"San Francisco , San Francisco, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Atala","sequence":"additional","affiliation":[{"name":"Wake Forest Institute for Regenerative Medicine , Winston-Salem, NC , USA"},{"name":"Wake Forest School of Medicine , Winston-Salem, NC , USA"},{"name":"Department of Urology , Winston-Salem, NC , USA"},{"name":"Wake Forest Baptist Medical Center , Winston-Salem, NC , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James J.","family":"Yoo","sequence":"additional","affiliation":[{"name":"Wake Forest Institute for Regenerative Medicine , Winston-Salem, NC , USA"},{"name":"Wake Forest School of Medicine , Winston-Salem, NC , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Wake Forest Institute for Regenerative Medicine , Winston-Salem, NC , USA"},{"name":"Wake Forest School of Medicine , Winston-Salem, NC , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Wake Forest Institute for Regenerative Medicine , Winston-Salem, NC , USA"},{"name":"Wake Forest School of Medicine , Winston-Salem, NC , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,1,27]]},"reference":[{"key":"2023011201062709100_bib1","article-title":"NIH National Cancer Institute. SEER Stat Fact Sheets: Prostate Cancer. Surveillance, Epidemiology, and End Results Program"},{"key":"2023011201062709100_bib2","first-page":"191","article-title":"Learning curve for robotic assisted laparoscopic prostatectomy: a multi-institutional study of 3794 patients","volume":"63","author":"Suriakumaran","year":"2011","journal-title":"Minerva Urol Nefrol"},{"key":"2023011201062709100_bib3","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.eururo.2012.04.046","article-title":"Prevention and management of postprostatectomy sexual dysfunctions. Part 1: choosing the right patient at the right time for the surgery","volume":"62","author":"Salonia","year":"2012","journal-title":"Eur Urol"},{"key":"2023011201062709100_bib4","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/S0140-6736(12)60520-0","article-title":"Erectile dysfunction","volume":"381","author":"Shamloul","year":"2013","journal-title":"Lancet"},{"key":"2023011201062709100_bib5","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1111\/j.1743-6109.2010.01804.x","article-title":"Erectile function rehabilitation in the radical prostatectomy patient","volume":"7","author":"Mulhall","year":"2010","journal-title":"J Sex Med"},{"key":"2023011201062709100_bib6","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.jsxm.2015.11.008","article-title":"Low-energy shock wave therapy ameliorates erectile dysfunction in a pelvic neurovascular injuries rat model","volume":"13","author":"Li","year":"2016","journal-title":"J Sex Med"},{"key":"2023011201062709100_bib7","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/j.eururo.2012.02.003","article-title":"Both immediate and delayed intracavernous injection of autologous adipose-derived stromalvascular fraction enhances recovery of erectile function in a rat model of cavernous nerve injury","volume":"62","author":"Qiu","year":"2012","journal-title":"Eur Urol"},{"key":"2023011201062709100_bib8","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.eururo.2012.09.034","article-title":"Intratunical injection of human adipose tissue-derived stem cells preventsfibrosis and is associated with improved erectile function in a rat model of Peyronie\u2019s disease","volume":"63","author":"Castiglione","year":"2013","journal-title":"Eur Urol"},{"key":"2023011201062709100_bib9","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.eururo.2011.07.061","article-title":"Recruitment of intracavernously injected adipose-derived stem cells to the major pelvic ganglion improves erectile function in a rat model of cavernous nerve injury","volume":"61","author":"Fandel","year":"2012","journal-title":"Eur Urol"},{"key":"2023011201062709100_bib10","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1016\/j.eururo.2015.09.026","article-title":"Safety of intracavernous bone marrow-mononuclear cells for postradical prostatectomy erectile dysfunction: an open dose-escalation pilot study","volume":"69","author":"Yiou","year":"2016","journal-title":"Eur Urol"},{"key":"2023011201062709100_bib11","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.3727\/096368916X691448","article-title":"Transplantation of human urine-derived stem cells transfected with pigment epithelium-derived factor to protect erectile function in a rat model of cavernous nerve injury","volume":"25","author":"Yang","year":"2016","journal-title":"Cell Transplant"},{"key":"2023011201062709100_bib12","doi-asserted-by":"crossref","first-page":"e92825","DOI":"10.1371\/journal.pone.0092825","article-title":"Human urine-derived stem cells alone or genetically-modified with FGF2 Improve type 2 diabetic erectile dysfunction in a rat model","volume":"9","author":"Ouyang","year":"2014","journal-title":"PLoS One"},{"key":"2023011201062709100_bib13","doi-asserted-by":"crossref","first-page":"155","DOI":"10.5534\/wjmh.2016.34.3.155","article-title":"The current status of stem-cell therapy in erectile dysfunction: a review","volume":"34","author":"Maldonado-Reed","year":"2016","journal-title":"World J Mens Health"},{"key":"2023011201062709100_bib14","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1111\/jsm.12957","article-title":"Intravenous preload of mesenchymal stem cells rescues erectile function in a rat model of erectile dysfunction","volume":"12","author":"Takayanagi","year":"2015","journal-title":"J Sex Med"},{"key":"2023011201062709100_bib15","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1111\/bju.14631","article-title":"Long-term therapeutic effect of cell therapy on improvement of erectile dysfunction in a rat model with pelvic neurovascular injury","volume":"124","author":"Gu","year":"2019","journal-title":"BJU Int"},{"key":"2023011201062709100_bib16","doi-asserted-by":"crossref","first-page":"e1104","DOI":"10.1016\/j.juro.2018.02.2728","article-title":"Non-invasive, dual-labeling, technology for cell tracking in stem cell therapy for erectile dysfunction","volume":"199","author":"Matz","year":"2018","journal-title":"J Urol"},{"key":"2023011201062709100_bib17","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/nbt1274","article-title":"Isolation of amniotic stem cell lines with potential for therapy","volume":"25","author":"De Coppi","year":"2007","journal-title":"Nat Biotechnol"},{"key":"2023011201062709100_bib18","doi-asserted-by":"crossref","first-page":"e72790","DOI":"10.1371\/journal.pone.0072790","article-title":"Correction of diabetic erectile dysfunction with adipose derived stem cells modified with the vascular endothelial growth factor gene in a rodent diabetic model","volume":"8","author":"Liu","year":"2013","journal-title":"PLoS One"},{"key":"2023011201062709100_bib19","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1111\/jsm.12380","article-title":"Intracavernous delivery of clonal mesenchymal stem cells restores erectile function in a mouse model of cavernous nerve injury","volume":"11","author":"Ryu","year":"2014","journal-title":"J Sex Med"},{"key":"2023011201062709100_bib20","doi-asserted-by":"crossref","first-page":"2439","DOI":"10.1111\/jsm.12636","article-title":"Therapeutic potential of adipose-derived stem cells-based micro-tissues in a rat model of postprostatectomy erectile dysfunction","volume":"11","author":"Xu","year":"2014","journal-title":"J Sex Med"},{"key":"2023011201062709100_bib21","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.3727\/096368913X667709","article-title":"Paracrine mechanisms of mesenchymal stem cell based therapy: current status and perspectives","volume":"23","author":"Liang","year":"2014","journal-title":"Cell Transpl"}],"container-title":["The Journal of Sexual Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1743609519318570?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1743609519318570?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jsm\/article-pdf\/17\/3\/400\/48527185\/jsm_17_3_400.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jsm\/article-pdf\/17\/3\/400\/48527185\/jsm_17_3_400.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T14:43:48Z","timestamp":1675953828000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jsm\/article\/17\/3\/400\/6973805"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,27]]},"references-count":21,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,1,27]]},"published-print":{"date-parts":[[2020,3,1]]}},"URL":"https:\/\/doi.org\/10.1016\/j.jsxm.2019.12.002","relation":{},"ISSN":["1743-6109","1743-6095"],"issn-type":[{"value":"1743-6109","type":"electronic"},{"value":"1743-6095","type":"print"}],"subject":[],"published-other":{"date-parts":[[2020,3]]},"published":{"date-parts":[[2020,1,27]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Dynamic Changes in Erectile Function and Histological Architecture After Intracorporal Injection of Human Placental Stem Cells in a Pelvic Neurovascular Injury Rat Model","name":"articletitle","label":"Article Title"},{"value":"The Journal of Sexual Medicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jsxm.2019.12.002","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}