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

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dc.contributor.authorSadeghi, Zhina
dc.contributor.authorIsariyawongse, Justin
dc.contributor.authorKavran, Michael
dc.contributor.authorIzgi, Kenan
dc.contributor.authorMarini, Gabriela [UNESP]
dc.contributor.authorMolter, Joseph
dc.contributor.authorDaneshgari, Firouz
dc.contributor.authorFlask, Chris A.
dc.contributor.authorCaplan, Arnold
dc.contributor.authorHijaz, Adonis
dc.contributor.institutionCase Western Reserve University
dc.contributor.institutionCase Western Reserve University School of Medicine
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.date.accessioned2022-04-29T07:26:53Z
dc.date.available2022-04-29T07:26:53Z
dc.date.issued2016-02-01
dc.description.abstractIntroduction 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.en
dc.description.affiliationUrology Institute University Hospitals of Case Medical Center Department of Urology Case Western Reserve University, 11100 Euclid Avenue
dc.description.affiliationDepartment of Urology Case Western Reserve University School of Medicine
dc.description.affiliationLaboratory of Experimental Research on Gynecology and Obstetrics Department of Gynecology and Obstetrics Botucatu Medical School
dc.description.affiliationDepartment of Radiology Case Western Reserve University
dc.description.affiliationDepartment of Biomedical Engineering Case Western Reserve University
dc.description.affiliationDepartment of Pediatrics Case Western Reserve University
dc.description.affiliationSkeletal Research Center Biology Department Case Western Reserve University
dc.description.affiliationUnespLaboratory of Experimental Research on Gynecology and Obstetrics Department of Gynecology and Obstetrics Botucatu Medical School
dc.description.sponsorshipNational Institute of Diabetes and Digestive and Kidney Diseases
dc.description.sponsorshipNational Institutes of Health
dc.description.sponsorshipIdNational Institute of Diabetes and Digestive and Kidney Diseases: 5K08DK090134
dc.description.sponsorshipIdNational Institutes of Health: 5K08DK090134
dc.format.extent291-300
dc.identifierhttp://dx.doi.org/10.1007/s00192-015-2831-5
dc.identifier.citationInternational Urogynecology Journal, v. 27, n. 2, p. 291-300, 2016.
dc.identifier.doi10.1007/s00192-015-2831-5
dc.identifier.issn1433-3023
dc.identifier.issn0937-3462
dc.identifier.scopus2-s2.0-84957435372
dc.identifier.urihttp://hdl.handle.net/11449/228109
dc.language.isoeng
dc.relation.ispartofInternational Urogynecology Journal
dc.sourceScopus
dc.subjectBirth-trauma injury
dc.subjectMesenchymal stem cell
dc.subjectMSC biodistribution
dc.subjectStem cell fate
dc.subjectStress urinary incontinence
dc.titleMesenchymal stem cell therapy in a rat model of birth-trauma injury: functional improvements and biodistributionen
dc.typeArtigo

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Artigos - Ginecologia e Obstetrícia - FMB