Mesenchymal Stem Cells Express the Surface Receptor Calreticulin (cC1qR) and Complement C1q Chemoattracts Them.
Notice bibliographique
Résumé
Abstract Abstract 3855 Complement cleavage fragments play an important role in the trafficking of hematopoietic stem/progenitor cells as reported by us (Blood 2003;101:3784; Exp Hematol 2010;38:321; Transfusion Sept 2010), as well as of mesenchymal stem cells (MSC) as reported by others (J Immunol 2009;182:3827). Because MSC have a great potential for tissue regeneration and cellular therapies, in this study we investigated the mechanisms of migration of MSC to injured sites. As complement cascade is activated upon tissue injury we examined whether complement component 1 subcomponent q (C1q), the initiator of the classical pathway of complement activation, plays a role in the migration of MSC, and which C1q receptors (CR1, gC1qR, calreticulin (cC1qR), CD93) are expressed on MSC and could be involved in their migration. We previously reported that matrix metalloproteinases (MMPs), especially membrane type 1 (MT1)-MMP and MMP-2, regulate the migration of MSC (Stem Cells, 2006, 24:1254); therefore in this study we examined the effects of C1q on MMP expression and migration of MSC. Human MSC isolated from cord blood and bone marrow were maintained for 3–6 passages and characterized by adipocyte and osteoblast differentiation. We used chemoinvasion across the reconstituted basement membrane Matrigel to evaluate the migration of MSC, RT-PCR and flow cytometry to determine the expression of C1q receptors and, upon stimulation with C1q, zymography and Western blot to examine the expression of MMPs and ERK1/2 and PI3K/Akt signaling pathways. We found that MSC were chemoattracted by a C1q gradient in a dose-dependent manner, and MSC expressed transcripts for gC1qR, CD93 and cC1qR, but only calreticulin protein was detected on the surface of MSC. Specific antibody against calreticulin (anti-cC1qR antibody) inhibited the trans-Matrigel chemoinvasion of MSC towards C1q. Moreover, stimulation of MSC with C1q (10 μ g/mL) increased MT1-MMP expression, but no changes in MMP-2 secretion were observed. Trans-Matrigel migration of MSC towards C1q was also reduced by the MT1-MMP inhibitor EGCG. Further, the ERK1/2 inhibitor PD98059 and the PI3K inhibitor Ly294002 decreased the chemoinvasion of MSC towards C1q. In conclusion, this study indicates that: 1) C1q exerts chemoattractant activity towards MSC through its surface receptor calreticulin; 2) MT1-MMP regulates the C1q-induced trans-Matrigel migration of MSC; and 3) both the ERK1/2 and PI3K/Akt signaling pathways are involved in this process. These findings demonstrate a broader regulatory role for C1q, which functions as a chemotactic factor for MSC through its binding to surface calreticulin, and suggest a newly-found mechanism for the migration of MSC which may be important for its clinical use. Disclosures: No relevant conflicts of interest to declare.
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 | 0,000 |
| 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 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 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 ».