158 - Prostate organoid model as a new model to study the crosstalk between epithelial and stromal cells in benign prostate hyperplasia
Notice bibliographique
Résumé
Hypothesis / aims of study Benign prostatic hyperplasia (BPH) is characterized by inflammation, fibrosis of the extracellular matrix and hypercontractility of stromal tissue. In urological diseases with similar symptoms, the ratio of pro nerve growth factor (proNGF) to its mature isoform (NGF) is increased and considered a marker of inflammation. Murine models of diabetic bladder dysfunction display the same imbalance. Chronic treatment with THX-B, an antagonist of the p75NTR receptor of proNGF, restored the neurotrophin ratio and improved bladder contractile parameters. On the other hand, organoids are tridimensional cellular structures which reproduce the interactions between different cell types present in the same organ, removing the problems associated with co-culturing cells in 2 dimensions. They have been widely used to study prostate diseases but mainly in cancer research. We here report a model of organoids from prostate cells to assess the role of neurotrophins in BPH. Study design, materials and methods Whole prostate tissue of Sprague-Dawley rats was digested with collagenase type II. Epithelial and stromal cells (50/50) were seeded in non-adherent wells. After 48 hours, the structure of organoids was examined by confocal microscopy using smooth muscle myosin heavy chain (SMMHC) and cytokeratin 17 (CK17) to highlight respectively stromal and epithelial cells. In the structure. BPH was induced with hyperglycemic medium (25 mM) combined or not with elevated testosterone concentrations (500 nM). THX-B, the antagonist of p75NTR proinflammatory receptor, was incubated in all conditions. Neurotrophin levels were measured by Elisa. Immunoblottings and RTqPCR were performed on cell extracts to assess inflammatory, contractility and fibrosis markers. Results Light microscopy revealed the organisation of cells into spheroids. Confocal microscopy showed epithelial and stromal cells mingled at the surface of a hollow structure, as revealed by CK17 (epithelial) and SMMHC (stromal) markers. Spheroids released NGF and proNGF in the culture medium. NGF secretion was not affected nor by high glucose nor testosterone combined or not, neither by THX-B. ProNGF levels were increased by testosterone and high glucose and reverted to contorl values by THX-B. Inflammatory markers IL1, IL-6 and TNF-alpha expression was unchanged in all conditions. Myosin, smoothelin and actin were unaffected. Interpretation of results Epithelial cells secrete many factors that directly target stromal cells. Co-culture in the form of organoids provide a new tool to examine how different cell type react in culture conditions mimicking a pathological settings, such as hyperglycemia and/or hypertestosteronemia. Concluding message Organoid culture of prostate cells was reproducible and constitute a valid model to study prostate cell interaction in BPH in the context of neurotrophin secretions. Funding Canadian urological asociation Clinical Trial No Subjects Animal Species rat Ethics Committee Canadian Council for Animal Care. All protocols and the Animal Ethics Committee of McGill University (Quebec, Canada).
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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) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,001 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 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 ».