TNF-alpha and hypoxia-induced paracrine secretion of rat bone marrow-mesenchymal stem cells for cardiac repair in Lewis rats post-ml
Notice bibliographique
Résumé
Bone-marrow mesenchymal stem cell (BM-MSC) strategies have been suggested to play a crucial role in promoting the reparative process in ischemic hearts following a myocardial infarction (MI). However, poor viability and retention of transplanted cells in the harsh microenvironment remains as an obstacle. The paracrine hypothesis suggests that BM-MSCs secrete paracrine factors consisting of biologically active molecules that may work together to manipulate the microenvironment and trigger angiogenesis, cardioprotective, and homing properties at the site of infarct. The current study aims to understand the regulatory effects of Tumour Necrosis Factor-α (TNF-α) and hypoxia on rat BM-MSCs (rBM-MSC) and the angiogenic, migratory, cardioprotective, and reparative effects of its secretion which may, initiate and sustain the process of cardiac repair post MI. Secretome from rBM-MSC cultures treated/untreated with either conditioned rat cardiomyocyte medium (rCCM), TNF-α, and/or normoxia/hypoxia in various combinations were examined. Immunocytochemistry and western blot analyses confirmed the presence of the TNF-Receptors 1 and 2 (TNFR1/TNFR2) on the surface of rBM-MSCs, which indicates that TNF-α is able to bind to rBM-MSCs and initiate cell survival pathways through the TNFR2 pathway. Western blot analyses on rBM-MSC lysates treated with rCCM, TNF-α and hypoxia showed increased expression of TGF-β, FGF-2, VEGF-1, Myogenin, and Ang-2. Thus, indicating that in hypoxic conditions, TNF-α induces rBM-MSCs to secrete proteins that contribute to neovascularization; MSC/endothelial cell (EC) proliferation, migration or differentiation; and/or decreasing acute pro-inflammatory responses. Furthermore, the trans-well migration assay showed that the TNF-α Hypoxia-Induced secretome exhibits chemotactic properties, which may play a role in the migration of BM-MSCs to the site of infarct. The Annexin V apoptosis assay revealed that the TNF-α Hypoxia-Induced secretome treatment on rCMs under hypoxia does not show a statistically significant difference between the values for the control cells (rCMS with hypoxia only) and itself. Accordingly, there may be no significant difference in the number of apoptotic rCMs, as the presence of the TNF-α cytokine itself may be reducing the pro-survival effect of the secreted secretome. In vivo, induced infarcted Lewis rats treated with TNF-α Hypoxia-Induced secretome had a higher left ventricle fractional shortening (LVFS) than the control secretome (rCCM and hypoxia) treated rats, while trichrome staining revealed a decrease in the size of infarct. Hence, a higher LVFS and the decrease in the size of infarct in the TNF-α hypoxia-induced secretome treated Lewis rats show that myocardial preservation maybe occurring. Lastly, immunohistochemistry revealed increased expression of CD31 and Ki67 proteins near the area of infarct in the TNF-α Hypoxia-Induced secretome treated rats. The presence of the CD31 and Ki67 markers indicate an increase in vessel formation and proliferation at the site of infarct in TNF-α hypoxia-induced secretome treated rats. These findings suggest that the paracrine secretion of TNF-α and hypoxia preconditioned BM-MSCs may play a therapeutic role in cardiac repair post-MI.
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 | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,001 |
| Méta-épidémiologie (sens large) | 0,002 | 0,001 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| 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 ».