Possible role of intravenous administration of mesenchymal stem cells to alleviate interstitial cystitis/bladder pain syndrome in a Toll-like receptor-7 agonist-induced experimental animal model in rat

Abstract Background Interstitial cystitis/bladder pain syndrome (IC/BPS) categorized with and without Hunner lesions is a condition that displays chronic pelvic pain related to the bladder with no efficacious treatment options. There are strong associations suggested between Hunner-type IC and autoi...

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Autores principales:	Hidetoshi Tabata, Masanori Sasaki, Yuko Kataoka-Sasaki, Nobuo Shinkai, Koji Ichihara, Naoya Masumori, Jeffery D. Kocsis, Osamu Honmou
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Intravenous Mesenchymal stem cell Hunner-type interstitial cystitis Diseases of the genitourinary system. Urology RC870-923
Acceso en línea:	https://doaj.org/article/a26989f9c6e448b0a5475d6b5788a594
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spelling	oai:doaj.org-article:a26989f9c6e448b0a5475d6b5788a5942021-11-14T12:30:54ZPossible role of intravenous administration of mesenchymal stem cells to alleviate interstitial cystitis/bladder pain syndrome in a Toll-like receptor-7 agonist-induced experimental animal model in rat10.1186/s12894-021-00923-31471-2490https://doaj.org/article/a26989f9c6e448b0a5475d6b5788a5942021-11-01T00:00:00Zhttps://doi.org/10.1186/s12894-021-00923-3https://doaj.org/toc/1471-2490Abstract Background Interstitial cystitis/bladder pain syndrome (IC/BPS) categorized with and without Hunner lesions is a condition that displays chronic pelvic pain related to the bladder with no efficacious treatment options. There are strong associations suggested between Hunner-type IC and autoimmune diseases. Recently, we established an animal model of Hunner-type IC using a Toll-like receptor-7 (TLR7) agonist. Intravenous infusion of mesenchymal stem cells (MSCs) can be used to treat injury via multimodal and orchestrated therapeutic mechanisms including anti-inflammatory effects. Here, we investigated whether infused MSCs elicit therapeutic efficacy associated with the TLR7-related anti-inflammatory pathway in our Hunner-type IC model. Methods Voiding behaviors were monitored 24 h prior to the Loxoribine (LX), which is a TLR7 agonist instillation in order to establish a Hunner-type IC model (from − 24 to 0 h) in female Sprague–Dawley rats. LX was instilled transurethrally into the bladder. At 0 h, the initial freezing behavior test confirmed that no freezing behavior was observed in any of the animals. The LX-instilled animals were randomized. Randomized LX-instilled rats were intravenously infused with MSCs or with vehicle through the right external jugular vein. Sampling tissue for green fluorescent protein (GFP)-positive MSCs were carried out at 48 h. Second voiding behavior tests were monitored from 72 to 96 h. After the final evaluation of the freezing behavior test at 96 h after LX instillation (72 h after MSC or vehicle infusion), histological evaluation with H&E staining and quantitative real-time polymerase chain reaction (RT-PCR) to analyze the mRNA expression levels of inflammatory cytokines were performed. Results Freezing behavior was reduced in the MSC group, and voiding behavior in the MSC group did not deteriorate. Hematoxylin–eosin staining showed that mucosal edema, leukocyte infiltration, and hemorrhage were suppressed in the MSC group. The relative expression of interferon-β mRNA in the bladder of the MSC group was inhibited. Numerous GFP-positive MSCs were distributed mainly in the submucosal and mucosal layers of the inflammatory bladder wall. Conclusion Intravenous infusion of MSCs may have therapeutic efficacy in a LX-instilled Hunner-type IC rat model via a TLR7-related anti-inflammatory pathway.Hidetoshi TabataMasanori SasakiYuko Kataoka-SasakiNobuo ShinkaiKoji IchiharaNaoya MasumoriJeffery D. KocsisOsamu HonmouBMCarticleIntravenousMesenchymal stem cellHunner-type interstitial cystitisDiseases of the genitourinary system. UrologyRC870-923ENBMC Urology, Vol 21, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Intravenous Mesenchymal stem cell Hunner-type interstitial cystitis Diseases of the genitourinary system. Urology RC870-923
spellingShingle	Intravenous Mesenchymal stem cell Hunner-type interstitial cystitis Diseases of the genitourinary system. Urology RC870-923 Hidetoshi Tabata Masanori Sasaki Yuko Kataoka-Sasaki Nobuo Shinkai Koji Ichihara Naoya Masumori Jeffery D. Kocsis Osamu Honmou Possible role of intravenous administration of mesenchymal stem cells to alleviate interstitial cystitis/bladder pain syndrome in a Toll-like receptor-7 agonist-induced experimental animal model in rat
description	Abstract Background Interstitial cystitis/bladder pain syndrome (IC/BPS) categorized with and without Hunner lesions is a condition that displays chronic pelvic pain related to the bladder with no efficacious treatment options. There are strong associations suggested between Hunner-type IC and autoimmune diseases. Recently, we established an animal model of Hunner-type IC using a Toll-like receptor-7 (TLR7) agonist. Intravenous infusion of mesenchymal stem cells (MSCs) can be used to treat injury via multimodal and orchestrated therapeutic mechanisms including anti-inflammatory effects. Here, we investigated whether infused MSCs elicit therapeutic efficacy associated with the TLR7-related anti-inflammatory pathway in our Hunner-type IC model. Methods Voiding behaviors were monitored 24 h prior to the Loxoribine (LX), which is a TLR7 agonist instillation in order to establish a Hunner-type IC model (from − 24 to 0 h) in female Sprague–Dawley rats. LX was instilled transurethrally into the bladder. At 0 h, the initial freezing behavior test confirmed that no freezing behavior was observed in any of the animals. The LX-instilled animals were randomized. Randomized LX-instilled rats were intravenously infused with MSCs or with vehicle through the right external jugular vein. Sampling tissue for green fluorescent protein (GFP)-positive MSCs were carried out at 48 h. Second voiding behavior tests were monitored from 72 to 96 h. After the final evaluation of the freezing behavior test at 96 h after LX instillation (72 h after MSC or vehicle infusion), histological evaluation with H&E staining and quantitative real-time polymerase chain reaction (RT-PCR) to analyze the mRNA expression levels of inflammatory cytokines were performed. Results Freezing behavior was reduced in the MSC group, and voiding behavior in the MSC group did not deteriorate. Hematoxylin–eosin staining showed that mucosal edema, leukocyte infiltration, and hemorrhage were suppressed in the MSC group. The relative expression of interferon-β mRNA in the bladder of the MSC group was inhibited. Numerous GFP-positive MSCs were distributed mainly in the submucosal and mucosal layers of the inflammatory bladder wall. Conclusion Intravenous infusion of MSCs may have therapeutic efficacy in a LX-instilled Hunner-type IC rat model via a TLR7-related anti-inflammatory pathway.
format	article
author	Hidetoshi Tabata Masanori Sasaki Yuko Kataoka-Sasaki Nobuo Shinkai Koji Ichihara Naoya Masumori Jeffery D. Kocsis Osamu Honmou
author_facet	Hidetoshi Tabata Masanori Sasaki Yuko Kataoka-Sasaki Nobuo Shinkai Koji Ichihara Naoya Masumori Jeffery D. Kocsis Osamu Honmou
author_sort	Hidetoshi Tabata
title	Possible role of intravenous administration of mesenchymal stem cells to alleviate interstitial cystitis/bladder pain syndrome in a Toll-like receptor-7 agonist-induced experimental animal model in rat
title_short	Possible role of intravenous administration of mesenchymal stem cells to alleviate interstitial cystitis/bladder pain syndrome in a Toll-like receptor-7 agonist-induced experimental animal model in rat
title_full	Possible role of intravenous administration of mesenchymal stem cells to alleviate interstitial cystitis/bladder pain syndrome in a Toll-like receptor-7 agonist-induced experimental animal model in rat
title_fullStr	Possible role of intravenous administration of mesenchymal stem cells to alleviate interstitial cystitis/bladder pain syndrome in a Toll-like receptor-7 agonist-induced experimental animal model in rat
title_full_unstemmed	Possible role of intravenous administration of mesenchymal stem cells to alleviate interstitial cystitis/bladder pain syndrome in a Toll-like receptor-7 agonist-induced experimental animal model in rat
title_sort	possible role of intravenous administration of mesenchymal stem cells to alleviate interstitial cystitis/bladder pain syndrome in a toll-like receptor-7 agonist-induced experimental animal model in rat
publisher	BMC
publishDate	2021
url	https://doaj.org/article/a26989f9c6e448b0a5475d6b5788a594
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Possible role of intravenous administration of mesenchymal stem cells to alleviate interstitial cystitis/bladder pain syndrome in a Toll-like receptor-7 agonist-induced experimental animal model in rat

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