PD09-08 INTRAPERITONEAL ADMINISTRATION OF MESENCHYMAL STEM CELLS IS EFFECTIVE IN PREVENTING DETRUSOR DYSFUNCTION AFTER PARTIAL BLADDER OUTLET OBSTRUCTION
Bibliographic record
Abstract
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 ...
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".