L-selectin and SDF-1 enhance the migration of mouse and human cardiac mesoangioblasts.
Résumé
Efficient delivery of stem cells to heart regions is still a major problem for cell therapy. Here, we report experiments aimed to improve migration of mouse and human cardiac mesoangioblasts to damaged heart. Cardiac mesoangioblasts were induced to transmigrate through the endothelium by factors released by cardiomyocytes or cytokines, among which SDF-1 was the most potent. Cardiac mesoangioblasts were also delivered into the left ventricular chamber of mice after coronary artery ligation (CAL) and their in vivo homing to the damaged heart was found to be quite modest. Pretreatment of cardiac mesoangioblasts with SDF-1 or transient expression of L-selectin induced a two to three fold increase in their transmigration and homing to the damaged heart. Therefore, combined pretreatment with SDF-1 and L-selectin generated modified cardiac mesoangioblasts, 50% of which, after injection into the LV chamber of mice early after CAL, home directly to damaged free wall of the heart. Finally, modified mouse cardiac mesoangioblasts, injected into the left ventricular chamber regenerate a larger surface of the ventricle in long-term experiments in comparison with their control counterparts. This study defines the requirements for efficient homing of cardiac mesoangioblasts to damaged heart and offers a new potent tool to optimize efficiency of future cell therapy protocols for cardiovascular diseases.
Domaines
Biologie cellulaire
Origine : Fichiers produits par l'(les) auteur(s)
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