EXTRACELLULAR VESICLES RELEASED FROM ENHANCED ADIPOSE TISSUE-DERIVED MESENCHYMAL STROMAL CELLS POLARIZE MACROPHAGES TOWARDS A DISTINCT IMMUNOMODULATORY PROFILE
Notice bibliographique
Résumé
Background & Aim Adipose tissue-derived mesenchymal stromal cells (MSC(AT)s possesses immunomodulatory capabilities that make them promising candidates for anti-inflammatory and regenerative applications. Their therapeutic effect is believed to be partially mediated by the release of small extracellular vesicles (sEVs). Previous work from our lab showed that MSC(AT)s treated under different non-genetic cell enhancement strategies significantly influenced their immunomodulatory fitness. This led us to hypothesize that enhanced MSC(AT)s would also produce sEVs with enhanced immunomodulatory activity. Furthermore, we investigated differences in the role of surface CD73-Ecto-5’-nucleotidase in sEV-mediated macrophage M2-like polarization between non-enhanced and enhanced MSC(AT)-sEVs. Methodology MSC(AT) grown to confluency were exposed to enhancement conditions: pro-inflammatory cytokine priming, 3D aggregation, and hypoxia. MSC(AT) conditioned media was collected and sEV fraction was isolated by differential ultracentrifugation. sEV was characterized by TEM and NTA. Protein count and identity were assessed by BCA and western blot, respectively. Peripheral blood-derived monocytes were differentiated to macrophages and treated with 10µg of non-enhanced or enhanced sEVs for 48 hours. Role of CD73 was assessed by incubating macrophages with CD73 inhibitor prior to sEV treatment. Macrophage polarization was assessed by TNFa secretion with ELISA, gene expression changes by RT-qPCR, and phagocytic ability by fluorescent bead uptake. Results There were no differences observed between non-enhanced and enhanced sEVs’ immunomodulatory activity. ELISA results showed that sEV conditions suppressed macrophage TNFa secretion to similar extents as M2 macrophage control. However, sEV conditions clustered together and distinctively from classical M1/M2 phenotypes, inducing a mixed pro- and anti-inflammatory profile. Lastly, ELISA results of CD73-inhibited macrophages showed significant reduction of TNFa suppression only for non-enhanced sEV and not for enhanced conditions. Conclusion While both sEV conditions can polarize macrophages towards an anti-inflammatory M2-like phenotype, non-genetic cell enhancement strategies could not produce sEVs with enhanced immunomodulatory capabilities. This likely implies that enhanced sEV are acting through different mechanisms of action than CD73-Ecto 5’-nucleotidase to achieve similar levels of polarization as non-enhanced sEV.
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,001 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
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 tête enseignante, 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 ».