{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:18:58Z","timestamp":1790662738857,"version":"4.1.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T00:00:00Z","timestamp":1655942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"},{"start":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T00:00:00Z","timestamp":1655942400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,7,23]],"date-time":"2023-07-23T00:00:00Z","timestamp":1690070400000},"content-version":"am","delay-in-days":395,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"name":"NIH\/NIDDK","award":["DK101536"],"award-info":[{"award-number":["DK101536"]}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK101536"],"award-info":[{"award-number":["DK101536"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","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":[[2022,8,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Cavernous nerve (CN) injury causes penile remodeling, including smooth muscle apoptosis and increased collagen, which results in erectile dysfunction (ED), and prevention of this remodeling is critical for novel ED therapy development.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Aim<\/jats:title>\n                  <jats:p>We developed 2 peptide amphiphile (PA) hydrogel delivery vehicles for Sonic hedgehog (SHH) protein to the penis and CN, which effectively suppress penile distrophic remodeling (apoptosis and fibrosis), in vivo in a rat CN injury model, and the aim of this study is to determine if SHH PA can be used to regenerate human corpora cavernosal smooth muscle deriving from multiple ED origins.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Corpora cavernosal tissue was obtained from prostatectomy, diabetic, hypertension, cardiovascular disease and Peyronie\u2019s (control) patients (n = 21). Primary cultures (n = 21) were established, and corpora cavernosal cells were treated with SHH protein, MSA (control), 5E1 SHH inhibitor, and PBS (control). Growth was quantified by counting the number of cells at 3\u20134 days. Statistics were performed by ANOVA with Scheffe\u2019s post hoc test. Concentration of SHH protein for maximal growth was optimized, and a more active SHH protein examined.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Outcomes<\/jats:title>\n                  <jats:p>Cultures were characterized by immunohistochemical analysis with ACTA2, CD31, nNOS and P4HB, and smooth muscle was quantified in comparison to DAPI.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Cultures established were &amp;gt;97% smooth muscle. SHH protein increased growth of smooth muscle cells from prostatectomy, diabetic, and Peyronie\u2019s patients in a similar manner (49%\u201351%), and SHH inhibition decreased growth (20%\u201333%). There was no difference in growth using 25 ug and 10 ug SHH protein, suggesting a threshold concentration of SHH protein above which smooth muscle growth is enhanced. A more active lipid modified SHH peptide further enhanced growth (15%), indicating a more robust growth response. SHH increased growth in smooth muscle cells from hypertension (37%) and cardiovascular disease (32%) patients. SHH protein increased growth under normal and high glucose conditions, suggesting that high glucose conditions that may be present in under controlled diabetic patients would not detract from SHH regenerative capacity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical Implications<\/jats:title>\n                  <jats:p>SHH PA would be beneficial to enhance smooth muscle regeneration in patients with ED of multiple etiologies.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Strengths and Limitations<\/jats:title>\n                  <jats:p>Understanding how human corpora cavernosal tissue responds to SHH treatment is critical for clinical translation of SHH PA to ED patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Corpora cavernosal smooth muscle from all ED patients responded to SHH treatment with increased growth.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1016\/j.jsxm.2022.04.010","type":"journal-article","created":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T04:31:26Z","timestamp":1655958686000},"page":"1228-1242","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":5,"title":["Sonic Hedgehog Signaling in Primary Culture of Human Corpora Cavernosal Tissue from Prostatectomy, Diabetic, and Peyronie\u2019s Patients"],"prefix":"10.1093","volume":"19","author":[{"given":"Sarah","family":"Martin","sequence":"first","affiliation":[{"name":"Department of Urology, University of Illinois at Chicago , Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangping","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Illinois at Chicago , Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Searl","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Illinois at Chicago , Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Ohlander","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Illinois at Chicago , Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel A.","family":"Harrington","sequence":"additional","affiliation":[{"name":"UTHealth, The University of Texas Health Science Center at Houston, Department of Diagnostic and Biomedical Sciences , Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel I.","family":"Stupp","sequence":"additional","affiliation":[{"name":"Materials Science and Engineering, Biomedical Engineering, and Medicine , Evanston, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danuta","family":"Dynda","sequence":"additional","affiliation":[{"name":"Division of Urology, Southern Illinois University School of Medicine , Springfield, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin T.","family":"McVary","sequence":"additional","affiliation":[{"name":"Department of Urology, Loyola University Stritch School of Medicine , Maywood, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol A.","family":"Podlasek","sequence":"additional","affiliation":[{"name":"Departments of Urology, Physiology, Bioengineering, and Biochemistry, University of Illinois at Chicago , Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,6,23]]},"reference":[{"key":"2023010703000406100_bib0001","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/S0022-5347(17)34871-1","article-title":"Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study","volume":"151","author":"Feldman","year":"1994","journal-title":"J Urol"},{"key":"2023010703000406100_bib0002","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1111\/j.1743-6109.04041.x","article-title":"Prevalence of erectile dysfunction among young adults: results of a large-scale survey","volume":"1","author":"Heruti","year":"2004","journal-title":"J Sex Med"},{"key":"2023010703000406100_bib0003","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.sxmr.2017.05.004","article-title":"Erectile dysfunction in young men\u2014a review of the prevalence and risk factors","volume":"5","author":"Nguyen","year":"2017","journal-title":"Sex Med Rev"},{"key":"2023010703000406100_bib0004","doi-asserted-by":"crossref","first-page":"87","DOI":"10.3816\/CGC.2004.n.017","article-title":"Current concepts in the management of erectile dysfunction in men with prostate cancer","volume":"3","author":"Kendirci","year":"2004","journal-title":"Clin Prostate Cancer"},{"key":"2023010703000406100_bib0005","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/S1470-2045(11)70162-0","article-title":"Long-term quality-of-life outcomes after radical prostatectomy or watchful waiting: the Scandinavian Prostate Cancer Group-4 randomised trial","volume":"12","author":"Johansson","year":"2011","journal-title":"Lancel Oncol"},{"key":"2023010703000406100_bib0006","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1097\/SPC.0000000000000195","article-title":"Erectile dysfunction after radical prostatectomy; prevalence, medical treatments, and psychosocial interventions","volume":"10","author":"Emanu","year":"2016","journal-title":"Curr Opin Support Palliat Care"},{"key":"2023010703000406100_bib0007","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1056\/NEJMoa1209978","article-title":"Long-term functional outcomes after treatment for localized prostate cancer","volume":"368","author":"Resnick","year":"2013","journal-title":"N Engl J Med"},{"key":"2023010703000406100_bib0008","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/S0889-8529(05)70329-7","article-title":"Diabetic sexual dysfunction","volume":"25","author":"Hakim","year":"1996","journal-title":"Endocrinol Metab Clin North Am"},{"key":"2023010703000406100_bib0009","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1111\/dme.13403","article-title":"High prevalence of erectile dysfunctionin diabetes; a systematic review and meta-analysis of 145 studies","volume":"34","author":"Kouidrat","year":"2017","journal-title":"Diabet Med"},{"key":"2023010703000406100_bib0010","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/S0302-2838(02)00032-5","article-title":"Switching from long-term treatment with self-injections to oral sildenafil in diabetic patients with severe erectile dysfunction","volume":"41","author":"Perimenis","year":"2002","journal-title":"Eur Urol"},{"key":"2023010703000406100_bib0011","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1016\/S0022-5347(01)64572-5","article-title":"Apoptosis in the rat penis after penile denervation","volume":"158","author":"Klein","year":"1997","journal-title":"J Urol"},{"key":"2023010703000406100_bib0012","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1097\/01.ju.0000048974.47461.50","article-title":"Penile weight and cell subtype specific changes in a post-radical prostatectomy model of erectile dysfunction","volume":"169","author":"User","year":"2003","journal-title":"J Urol"},{"key":"2023010703000406100_bib0013","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1095\/biolreprod.102.013508","article-title":"Altered sonic hedgehog signaling is associated with morphological abnormalities in the penis of the BB\/WOR diabetic rat","volume":"69","author":"Podlasek","year":"2003","journal-title":"Biol Reprod"},{"key":"2023010703000406100_bib0014","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1095\/biolreprod.106.053926","article-title":"Regulation of cavernous nerve injury-induced apoptosis by sonic hedgehog","volume":"76","author":"Podlasek","year":"2007","journal-title":"Biol Reprod"},{"key":"2023010703000406100_bib0015","doi-asserted-by":"crossref","first-page":"e70985","DOI":"10.1371\/journal.pone.0070985","article-title":"Sonic hedgehog protein is decreased and penile morphology is altered in prostatectomy and diabetic patients","volume":"8","author":"Angeloni","year":"2013","journal-title":"PLoS One"},{"key":"2023010703000406100_bib0016","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.actbio.2016.01.014","article-title":"Sonic hedgehog delivery from self-assembled nanofiber hydrogels reduces the fibrotic response in models of erectile dysfunction","volume":"32","author":"Choe","year":"2016","journal-title":"Acta Biomater"},{"key":"2023010703000406100_bib0017","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1095\/biolreprod.102.006643","article-title":"Sonic hedgehog cascade is required for penile postnatal morphogenesis, differentiation and adult homeostasis","volume":"68","author":"Podlasek","year":"2003","journal-title":"Biol Reprod"},{"key":"2023010703000406100_bib0018","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1111\/j.1743-6109.2012.02930.x","article-title":"Sonic hedgehog is neuroprotective in the cavernous nerve with crush injury","volume":"10","author":"Angeloni","year":"2013","journal-title":"J Sex Med"},{"key":"2023010703000406100_bib0019","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1095\/biolreprod.107.064766","article-title":"Neural influences on sonic hedgehog and apoptosis in the penis","volume":"78","author":"Bond","year":"2008","journal-title":"Biol Reprod"},{"key":"2023010703000406100_bib0020","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1126\/science.1063187","article-title":"Self-assembly and mineralization of peptide-amphiphile nanofibers","volume":"294","author":"Hartgerink","year":"2001","journal-title":"Science"},{"key":"2023010703000406100_bib0021","doi-asserted-by":"crossref","first-page":"5133","DOI":"10.1073\/pnas.072699999","article-title":"Peptide-amphiphile nanofibers: a versatile scaffold for the preparation of self-assembling materials","volume":"99","author":"Hartgerink","year":"2002","journal-title":"Proc Natl Acad Sci USA"},{"key":"2023010703000406100_bib0022","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1038\/nmat2778","article-title":"A self-assembly pathway to aligned monodomain gels","volume":"9","author":"Zhang","year":"2010","journal-title":"Nat Mater"},{"key":"2023010703000406100_bib0023","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1111\/j.1743-6109.2010.02001.x","article-title":"Peptide amphiphile nanofiber delivery of sonic hedgehog protein to reduce smooth muscle apoptosis in the penis after cavernous nerve resection","volume":"8","author":"Bond","year":"2011","journal-title":"J Sex Med"},{"key":"2023010703000406100_bib0024","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1016\/j.biomaterials.2010.10.003","article-title":"Regeneration of the cavernous nerve by Sonic hedgehog using aligned peptide amphiphile nanofibers","volume":"32","author":"Angeloni","year":"2011","journal-title":"Biomaterials"},{"key":"2023010703000406100_bib0025","article-title":"Optimization of Sonic hedgehog delivery to the penis from self-assembling nanofiber hydrogels to preserve penile morphology after cavernous nerve injury","volume":"20","author":"Choe","year":"2019","journal-title":"Nanomedicine"},{"key":"2023010703000406100_bib0026","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1111\/j.1464-410X.2008.08023.x","article-title":"Stereological and biochemical analysis of muscular and connective tissue components in the penile corpus cavernosum adjacent to the fibrous plaque of Peyronie\u2019s disease","volume":"103","author":"Costa","year":"2008","journal-title":"BJU Int"},{"key":"2023010703000406100_bib0027","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/BF00749976","article-title":"A rapid preparation of primary cultures of mouse skeletal muscle cells","volume":"13","author":"Metzinger","year":"1993","journal-title":"Cytotechnology"},{"key":"2023010703000406100_bib0028","doi-asserted-by":"crossref","first-page":"2551","DOI":"10.1002\/nau.23813","article-title":"Sonic hedgehog regulation of human rhabdosphincter muscle: potential implications for treatment of stress urinary incontinence","volume":"37","author":"Hehemann","year":"2018","journal-title":"Neurourol Urodyn"},{"key":"2023010703000406100_bib0029","doi-asserted-by":"crossref","first-page":"4011","DOI":"10.2174\/138161205774913408","article-title":"Sonic hedgehog, the penis and erectile dysfunction: a review of Sonic Hedgehog in the penis","volume":"11","author":"Podlasek","year":"2005","journal-title":"Curr Pharm Design"}],"container-title":["The Journal of Sexual Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1743609522013029?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1743609522013029?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jsm\/article-pdf\/19\/8\/1228\/48420898\/jsm_19_8_1228.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jsm\/article-pdf\/19\/8\/1228\/48420898\/jsm_19_8_1228.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T14:53:51Z","timestamp":1675954431000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jsm\/article\/19\/8\/1228\/6961369"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,23]]},"references-count":29,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,6,23]]},"published-print":{"date-parts":[[2022,8,1]]}},"URL":"https:\/\/doi.org\/10.1016\/j.jsxm.2022.04.010","relation":{},"ISSN":["1743-6109","1743-6095"],"issn-type":[{"value":"1743-6109","type":"electronic"},{"value":"1743-6095","type":"print"}],"subject":[],"published-other":{"date-parts":[[2022,8]]},"published":{"date-parts":[[2022,6,23]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Sonic Hedgehog Signaling in Primary Culture of Human Corpora Cavernosal Tissue From Prostatectomy, Diabetic, and Peyronie's Patients","name":"articletitle","label":"Article Title"},{"value":"The Journal of Sexual Medicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jsxm.2022.04.010","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Published by Elsevier Inc on behalf of the International Society for Sexual Medicine","name":"copyright","label":"Copyright"}]}}