Bradycardic mice undergo effective heart rate improvement after specific homing to the sino-atrial node and differentiation of adult muscle derived stem cells - Université Paris Cité Accéder directement au contenu
Pré-Publication, Document De Travail Nature Communications Année : 2019

Bradycardic mice undergo effective heart rate improvement after specific homing to the sino-atrial node and differentiation of adult muscle derived stem cells

Résumé

Current treatment for heart automaticity disorders still lack a safe and efficient source of stem cells to bring about biological pacemaking. Since adult Muscle-Derived Stem Cells (MDSC) show multi- lineage differentiation in vitro including into spontaneously beating cardiomyocytes, we questioned whether MDSCs could effectively differentiate into cardiac pacemakers, a specific population of myocytes producing electrical impulses in the sino-atrial node of adult heart. We show here that beating cardiomyocytes, differentiated from MDSC in vitro, exhibit typical characteristics of cardiac pacemakers: the expression of Hcn4, Tbx3 and Islet1, as well as spontaneous calcium transients and hyperpolarization-activated “funny” current, a unique signature of sino-atrial pacemakers. Pacemaker-like myocytes differentiated in vitro from Cav1.3 -deficient mouse MDSC produced slower Ca2+ transients, consistent with the reduction of native pacemaker activity in these mice. In vivo, systemic injection of undifferentiated wild type MDSCs into bradycardic mutant Ca 1.3-/- mice was ensued by their migration and homing to the sino-atrial node area within 48h and differentiation into Cav1.3 -expressing pacemaker-like myocytes within 10 days, a process accompanied by a significant improvement of the heart rate after 10 days that was maintained for up to 5 weeks. These findings identify MDSCs as directly transplantable stem cells that efficiently engraft, differentiate and improve heart rhythm in a mouse model of congenital bradycardia.
Fichier principal
Vignette du fichier
Mesreca_et_al_2019_preprint.pdf (1.52 Mo) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)
Loading...

Dates et versions

hal-02394274 , version 1 (04-12-2019)

Identifiants

Citer

Pietro Mesirca, Daria Mamaeva, Isabelle Bidaud, Romain Davaze, Mattia L Difrancesco, et al.. Bradycardic mice undergo effective heart rate improvement after specific homing to the sino-atrial node and differentiation of adult muscle derived stem cells. 2018. ⟨hal-02394274⟩
77 Consultations
80 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More