PD09-08 INTRAPERITONEAL ADMINISTRATION OF MESENCHYMAL STEM CELLS IS EFFECTIVE IN PREVENTING DETRUSOR DYSFUNCTION AFTER PARTIAL BLADDER OUTLET OBSTRUCTION
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Résumé
You have accessJournal of UrologyStem Cell Research (PD09)1 Apr 2019PD09-08 INTRAPERITONEAL ADMINISTRATION OF MESENCHYMAL STEM CELLS IS EFFECTIVE IN PREVENTING DETRUSOR DYSFUNCTION AFTER PARTIAL BLADDER OUTLET OBSTRUCTION Bridget Waife, Tom Churchill, Rutuja Kadam, Jennifer Carleton, Adetola Adesida, and Peter Metcalfe* Bridget WaifeBridget Waife More articles by this author , Tom ChurchillTom Churchill More articles by this author , Rutuja KadamRutuja Kadam More articles by this author , Jennifer CarletonJennifer Carleton More articles by this author , Adetola AdesidaAdetola Adesida More articles by this author , and Peter Metcalfe*Peter Metcalfe* More articles by this author View All Author Informationhttps://doi.org/10.1097/01.JU.0000555266.36014.0fAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVES: Mesenchymal stem cells (MSC) have shown great promise with respect to the prevention and treatment of detrusor dysfunction and fibrosis after partial bladder outlet obstruction (pBOO). Our lab has previously demonstrated short and long-term benefits with a reduction in the inflammatory and hypoxic cytokine cascade, decreased smooth muscle hypertrophy, prevention of fibrosis, and improvement in urodynamic parameters. Although our intravenous administration has demonstrated uptake of MSC into the bladder, we hypothesize the primary mechanism of action is via a systemic downregulation of the inflammatory and hypoxic cascade. Therefore, we repeated the pBOO in our model using the intraperitoneal (IP) administration of MSC to compare the efficacy to intravenous administration. METHODS: 5x106 MSC via IP had similar effects to 106 MSC IV, while 106 IP was not as effective. 5 x106 IP showed greater reduction in TGF-B1, MTOR, and Col 1+3 than 106 IV (p<0.05) at 4 weeks. The difference was less pronounced after 2 weeks. MSC benefits were seen with respect to decreased hypoxic markers (HIF-1, HIF-3) and improved urodynamic parameters, with the high dose IP results similar to the IV administration. IHC demonstrated uptake of MSC in the detrusor with IV, but not with IP dosing. RESULTS: 5x106 MSC via IP had similar effects to 106 MSC IV, while 106 IP was not as effective. 5 x106 IP showed greater reduction in TGF-B1, MTOR, and Col 1+3 than 106 IV (p<0.05) at 4 weeks. The difference was less pronounced after 2 weeks. MSC benefits were seen with respect to decreased hypoxic markers (HIF-1, HIF-3) and improved urodynamics, with the high dose IP results similar to the IV administration. IHC demonstrated MSC in the detrusor with IV, but not with IP dosing. CONCLUSIONS: We have been able to show that IP MSC administration is effective in a dose and time dependent manner. IP compares favorably to IV administration but requires greater dosing. Its mechanism of action, however, may demonstrate a distant response to systemic inflammation compared to detrusor implantation and direct, paracrine responses. This has significant implications with respect to the comprehension of the mechanism of action and progression to clinical use. Source of Funding: Rex Boake Summer Studentship William Lakey Summer Studentship CUA Astellas Research Grant Edmonton Civic Employees Edmonton, Canada© 2019 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 201Issue Supplement 4April 2019Page: e156-e156 Advertisement Copyright & Permissions© 2019 by American Urological Association Education and Research, Inc.MetricsAuthor Information Bridget Waife More articles by this author Tom Churchill More articles by this author Rutuja Kadam More articles by this author Jennifer Carleton More articles by this author Adetola Adesida More articles by this author Peter Metcalfe* More articles by this author Expand All Advertisement PDF downloadLoading ...
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,006 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».