Circulating bone marrow-derived precursor cells modulate the wound healing outcome by cell transdifferentiation
Notice bibliographique
Résumé
Normal wound healing process is a regulated biological response of multiple events whose common aim is to restore the integrity of injured tissues. Fibroblasts exert an important role in this process as target cells that allow either tissue remodeling through the predominant production of proteases (i.e., matrix metalloproteinases) or tissue fibrosis through the over-expression of extracellular matrix (ECM) components such as collagens. However, it remains unclear which factors activate such diversity of fibroblast responses and how this decision making process is made. Currently, there is no a well established model that integrally explains the diversity of responses from minimal to hypertropic scarring and keloids. Previous reports have demonstrated that some recruited cells can be locally transformed into fibrocytes, a pro-fibrogenic cells that stimulate resident fibroblasts to produce collagen accumulation and tissue fibrosis. However, recruited cells with anti-fibrogenic profile that can compete with and eventually reverse the local effects of fibrocytes have not been identified. How the skin maintains the cell transdifferentiation balance in normal wound healing and how this balance is modified in fibro-proliferative cutaneous disorders cannot be entirely explained by pro-fibrogenic fibrocytes without anti-fibrogenic counterparts. This doctoral thesis hypothesizes a novel mechanism in which bone marrow-derived cells recruited to the injured area modulate the expression of ECM components produced by resident fibroblasts. As a result of the tissue injury, a repertoire of systemic and local cytokines and growth factors induce epigenetic changes and cell transdifferentiation in circulating recruited cells. Thus, these locally transformed cells can acquire either pro- or anti-fibrogenic profile, and more importantly, they can induce the production of either collagens or MMPs by dermal fibroblasts. This study demonstrates that circulating stem cells and monocytes have the capacity to transdifferentiate into keratincoyte-like cells (KLCs), anti-fibrogenic cells that increase the expression MMPs by themselves and by the stimulation of dermal fibroblasts. The transdifferentiation of pro-fibrogenic fibrocytes into KLCs was also studied. In all cases the TGF-β deprivation was identified as crucial factor in the anti-fibrotic commitment of recruited cells. Finally, adipofascial groin flaps in rats were utilized as in vivo model to study the role of the tissue repair microenvironment in the cell transdifferentiation of recruited bone marrow-derived cells. The findings presented in this thesis are consistent with the existence of a "seesaw mechanism" in the regulation of MMPs/collagen production by dermal fibroblasts. Thus, during the wound-healing response, the local environment may induce epigenetic changes in recruited bone marrow-derived cells to follow either pro- or anti-fibrogenic pathways. Subsequently, these committed cells may trigger a fibro-proliferative switch on resident fibroblasts to predominantly develop either collagen accumulation with tissue fibrosis or collagen breakdown with tissues remodeling. Findings of this doctoral thesis provide new insights into the role of cell transdifferentiation and local environment not only in wound healing, but may also in other fibro-proliferative processes such as lung fibrosis, asthma, liver cirrhosis, chronic pancreatitis, and atherosclerosis, among others.
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 | 0,001 | 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) | 0,004 | 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 ».