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
Background: Due to the limited regenerative capacity of mammalian cardiomyocytes, following a myocardial infarction (MI) the chronic loss of functional contractile myocardium and continuous inflammation degrade the structure and function of the heart.Although bone-marrow mesenchymal stem cell (BM-MSC) strategies have been suggested to play a crucial role in promoting the repairing process in ischemic hearts, 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.Tumour Necrosis Factor-α (TNF-α) is a pleiotropic proinflammatory cytokine present in ischemic cardiac regions, but the specific roles it plays in cardioprotection and its interaction with BM-MSCs have yet to be established.The current study aims to understand the regulatory effects of TNF-α and hypoxia on rat BM-MSCs (rBM-MSC) and the angiogenic, migratory, cardioprotective, and reparative effects of its secretions which may, initiate and sustain the process of cardiac repair following MI.Methods: Secretome from rBM-MSC cultures treated/untreated with either conditioned rat cardiomyocyte medium (rCCM), TNF-α, and/or normoxia/hypoxia in various combinations were collected.Immunocytochemistry, western blot analyses, trans-well cell migration, and Annexin V apoptosis assays in conjunction with fluorescence-activated cell sorting were conducted.In vivo, echocardiography was performed on induced infarcted rats at three weeks following their treatment with a control (rCCM and hypoxia) or TNF-α Hypoxia-Induced secretome.Histological analyses including Masson's Trichrome staining and immunohistochemistry (IHC) for the CD31 and Ki-67 markers were further conducted.Image J and Prism were used for graphing and statistical analysis.Results: The immunocytochemistry and western blot analyses confirmed the presence of the TNF-Receptors 1 and 2 (TNFR1/TNFR2) on the surface of rBM-MSCs.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, while decreased expression of Ang-1 and FGF-7.The trans-well migration assay showed that TNF-α Hypoxia-Induced secretome exhibits chemotactic properties.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 for providing me with the opportunity to experience the highest level of translational research in the field of cardiology at the MUHC's Myocardial Regeneration Lab.Thank you for your kind support and guidance throughout this journey in helping me fulfill my passion in research and further advancing my knowledge in the field of cardiac research.I would like to extend my sincere thanks to the members of my advisory committee: Dr. Maria Petropavlovskaya, Dr. Fackson Mwale, and Dr. Jacques Lapointe for their time, support, and contributions to furthering my knowledge and for challenging me in successfully understanding and acquiring the skills and knowledge required to excel as a graduate student.I would like to offer my special
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) | 0,000 | 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 | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 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 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 ».