Mesenchymal stem cell therapy in a rat model of birth-trauma injury: functional improvements and biodistribution

Detalhes bibliográficos
Autor(a) principal: Sadeghi, Zhina
Data de Publicação: 2016
Outros Autores: Isariyawongse, Justin, Kavran, Michael, Izgi, Kenan, Marini, Gabriela [UNESP], Molter, Joseph, Daneshgari, Firouz, Flask, Chris A., Caplan, Arnold, Hijaz, Adonis
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1007/s00192-015-2831-5
http://hdl.handle.net/11449/228109
Resumo: Introduction and hypothesis: We evaluated the potential role of human mesenchymal stem cells (hMSCs) in improvement of urinary continence following birth-trauma injury. Methods: Human MSCs were injected periurethrally or systemically into rats immediately after vaginal distention (VD) (n = 90). Control groups were non-VD (uninjured/untreated, n = 15), local or systemic saline (injection/control, n = 90), and dermofibroblast (cell therapy/control, n = 90). Leak-point pressure (LPP) was measured 4, 10, and 14 days later. Urethras were morphometrically evaluated. In another sets of VD and non-VD rats, the fate of periurethrally injected hMSC, biodistribution, and in vivo viability was studied using human Alu genomic repeat staining, PKH26 labeling, and luciferase-expression labeling, respectively. Results: Saline- and dermofibroblast-treated control rats demonstrated lower LPP than non-VD controls at days 4 and 14 (P < 0.01). LPP after systemic hMSC and periurethral hMSC treatment were comparable with non-VD controls at 4, 10, and 14 days (P > 0.05). Local saline controls demonstrated extensive urethral tissue bleeding. The connective tissue area/urethral section area proportion and vascular density were higher in the local hMSC- versus the saline-treated group at 4 and 14 days, respectively. No positive Alu-stained nuclei were observed in urethras at 4, 10, and 14 days. PKH26-labelled cells were found in all urethras at 2 and 24 h. Bioluminescence study showed increased luciferase expression from day 0 to 1 following hMSC injection. Conclusions: Human MSCs restored the continence mechanism with an immediate and sustained effect in the VD model, while saline and dermofibroblast therapy did not. Human MSCs remained at the site of periurethral injection for <7 days. We hypothesize that periurethral hMSC treatment improves vascular, connective tissue, and hemorrhage status of urethral tissues after acute VD injury.
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spelling Mesenchymal stem cell therapy in a rat model of birth-trauma injury: functional improvements and biodistributionBirth-trauma injuryMesenchymal stem cellMSC biodistributionStem cell fateStress urinary incontinenceIntroduction and hypothesis: We evaluated the potential role of human mesenchymal stem cells (hMSCs) in improvement of urinary continence following birth-trauma injury. Methods: Human MSCs were injected periurethrally or systemically into rats immediately after vaginal distention (VD) (n = 90). Control groups were non-VD (uninjured/untreated, n = 15), local or systemic saline (injection/control, n = 90), and dermofibroblast (cell therapy/control, n = 90). Leak-point pressure (LPP) was measured 4, 10, and 14 days later. Urethras were morphometrically evaluated. In another sets of VD and non-VD rats, the fate of periurethrally injected hMSC, biodistribution, and in vivo viability was studied using human Alu genomic repeat staining, PKH26 labeling, and luciferase-expression labeling, respectively. Results: Saline- and dermofibroblast-treated control rats demonstrated lower LPP than non-VD controls at days 4 and 14 (P < 0.01). LPP after systemic hMSC and periurethral hMSC treatment were comparable with non-VD controls at 4, 10, and 14 days (P > 0.05). Local saline controls demonstrated extensive urethral tissue bleeding. The connective tissue area/urethral section area proportion and vascular density were higher in the local hMSC- versus the saline-treated group at 4 and 14 days, respectively. No positive Alu-stained nuclei were observed in urethras at 4, 10, and 14 days. PKH26-labelled cells were found in all urethras at 2 and 24 h. Bioluminescence study showed increased luciferase expression from day 0 to 1 following hMSC injection. Conclusions: Human MSCs restored the continence mechanism with an immediate and sustained effect in the VD model, while saline and dermofibroblast therapy did not. Human MSCs remained at the site of periurethral injection for <7 days. We hypothesize that periurethral hMSC treatment improves vascular, connective tissue, and hemorrhage status of urethral tissues after acute VD injury.National Institute of Diabetes and Digestive and Kidney DiseasesNational Institutes of HealthUrology Institute University Hospitals of Case Medical Center Department of Urology Case Western Reserve University, 11100 Euclid AvenueDepartment of Urology Case Western Reserve University School of MedicineLaboratory of Experimental Research on Gynecology and Obstetrics Department of Gynecology and Obstetrics Botucatu Medical SchoolDepartment of Radiology Case Western Reserve UniversityDepartment of Biomedical Engineering Case Western Reserve UniversityDepartment of Pediatrics Case Western Reserve UniversitySkeletal Research Center Biology Department Case Western Reserve UniversityLaboratory of Experimental Research on Gynecology and Obstetrics Department of Gynecology and Obstetrics Botucatu Medical SchoolNational Institute of Diabetes and Digestive and Kidney Diseases: 5K08DK090134National Institutes of Health: 5K08DK090134Case Western Reserve UniversityCase Western Reserve University School of MedicineUniversidade Estadual Paulista (UNESP)Sadeghi, ZhinaIsariyawongse, JustinKavran, MichaelIzgi, KenanMarini, Gabriela [UNESP]Molter, JosephDaneshgari, FirouzFlask, Chris A.Caplan, ArnoldHijaz, Adonis2022-04-29T07:26:53Z2022-04-29T07:26:53Z2016-02-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article291-300http://dx.doi.org/10.1007/s00192-015-2831-5International Urogynecology Journal, v. 27, n. 2, p. 291-300, 2016.1433-30230937-3462http://hdl.handle.net/11449/22810910.1007/s00192-015-2831-52-s2.0-84957435372Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengInternational Urogynecology Journalinfo:eu-repo/semantics/openAccess2024-08-16T14:12:50Zoai:repositorio.unesp.br:11449/228109Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-16T14:12:50Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Mesenchymal stem cell therapy in a rat model of birth-trauma injury: functional improvements and biodistribution
title Mesenchymal stem cell therapy in a rat model of birth-trauma injury: functional improvements and biodistribution
spellingShingle Mesenchymal stem cell therapy in a rat model of birth-trauma injury: functional improvements and biodistribution
Sadeghi, Zhina
Birth-trauma injury
Mesenchymal stem cell
MSC biodistribution
Stem cell fate
Stress urinary incontinence
title_short Mesenchymal stem cell therapy in a rat model of birth-trauma injury: functional improvements and biodistribution
title_full Mesenchymal stem cell therapy in a rat model of birth-trauma injury: functional improvements and biodistribution
title_fullStr Mesenchymal stem cell therapy in a rat model of birth-trauma injury: functional improvements and biodistribution
title_full_unstemmed Mesenchymal stem cell therapy in a rat model of birth-trauma injury: functional improvements and biodistribution
title_sort Mesenchymal stem cell therapy in a rat model of birth-trauma injury: functional improvements and biodistribution
author Sadeghi, Zhina
author_facet Sadeghi, Zhina
Isariyawongse, Justin
Kavran, Michael
Izgi, Kenan
Marini, Gabriela [UNESP]
Molter, Joseph
Daneshgari, Firouz
Flask, Chris A.
Caplan, Arnold
Hijaz, Adonis
author_role author
author2 Isariyawongse, Justin
Kavran, Michael
Izgi, Kenan
Marini, Gabriela [UNESP]
Molter, Joseph
Daneshgari, Firouz
Flask, Chris A.
Caplan, Arnold
Hijaz, Adonis
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Case Western Reserve University
Case Western Reserve University School of Medicine
Universidade Estadual Paulista (UNESP)
dc.contributor.author.fl_str_mv Sadeghi, Zhina
Isariyawongse, Justin
Kavran, Michael
Izgi, Kenan
Marini, Gabriela [UNESP]
Molter, Joseph
Daneshgari, Firouz
Flask, Chris A.
Caplan, Arnold
Hijaz, Adonis
dc.subject.por.fl_str_mv Birth-trauma injury
Mesenchymal stem cell
MSC biodistribution
Stem cell fate
Stress urinary incontinence
topic Birth-trauma injury
Mesenchymal stem cell
MSC biodistribution
Stem cell fate
Stress urinary incontinence
description Introduction and hypothesis: We evaluated the potential role of human mesenchymal stem cells (hMSCs) in improvement of urinary continence following birth-trauma injury. Methods: Human MSCs were injected periurethrally or systemically into rats immediately after vaginal distention (VD) (n = 90). Control groups were non-VD (uninjured/untreated, n = 15), local or systemic saline (injection/control, n = 90), and dermofibroblast (cell therapy/control, n = 90). Leak-point pressure (LPP) was measured 4, 10, and 14 days later. Urethras were morphometrically evaluated. In another sets of VD and non-VD rats, the fate of periurethrally injected hMSC, biodistribution, and in vivo viability was studied using human Alu genomic repeat staining, PKH26 labeling, and luciferase-expression labeling, respectively. Results: Saline- and dermofibroblast-treated control rats demonstrated lower LPP than non-VD controls at days 4 and 14 (P < 0.01). LPP after systemic hMSC and periurethral hMSC treatment were comparable with non-VD controls at 4, 10, and 14 days (P > 0.05). Local saline controls demonstrated extensive urethral tissue bleeding. The connective tissue area/urethral section area proportion and vascular density were higher in the local hMSC- versus the saline-treated group at 4 and 14 days, respectively. No positive Alu-stained nuclei were observed in urethras at 4, 10, and 14 days. PKH26-labelled cells were found in all urethras at 2 and 24 h. Bioluminescence study showed increased luciferase expression from day 0 to 1 following hMSC injection. Conclusions: Human MSCs restored the continence mechanism with an immediate and sustained effect in the VD model, while saline and dermofibroblast therapy did not. Human MSCs remained at the site of periurethral injection for <7 days. We hypothesize that periurethral hMSC treatment improves vascular, connective tissue, and hemorrhage status of urethral tissues after acute VD injury.
publishDate 2016
dc.date.none.fl_str_mv 2016-02-01
2022-04-29T07:26:53Z
2022-04-29T07:26:53Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1007/s00192-015-2831-5
International Urogynecology Journal, v. 27, n. 2, p. 291-300, 2016.
1433-3023
0937-3462
http://hdl.handle.net/11449/228109
10.1007/s00192-015-2831-5
2-s2.0-84957435372
url http://dx.doi.org/10.1007/s00192-015-2831-5
http://hdl.handle.net/11449/228109
identifier_str_mv International Urogynecology Journal, v. 27, n. 2, p. 291-300, 2016.
1433-3023
0937-3462
10.1007/s00192-015-2831-5
2-s2.0-84957435372
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv International Urogynecology Journal
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 291-300
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
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