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Myoblasts and Embryonic Stem Cells Differentially Engraft in a Mouse Model of Genetic Dilated Cardiomyopathy

Authors :
Gisèle Bonne
Gillian Butler-Browne
Karine Vauchez
Adeline Jacquet
Marc Fiszman
Erica Yada
Cyril Catelain
Nathalie Mougenot
Michel Pucéat
Aurélie Papadopoulos
Jean-Thomas Vilquin
Stéphanie Riveron
Vilquin, Jean-Thomas
Centre de recherche en Myologie – U974 SU-INSERM
Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
CHU Pitié-Salpêtrière [AP-HP]
Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Institut de Myologie
Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Génétique, pharmacologie et physiopathologie des maladies cardiovasculaires
Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Therapie Cellulaire en Pathologie Cardio-Vasculaire (UMR_S 633)
Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Source :
Molecular Therapy, Molecular Therapy, 2013, 21 (5), pp.1064-1075. ⟨10.1038/mt.2013.15⟩, Molecular Therapy; Vol 21
Publication Year :
2013
Publisher :
HAL CCSD, 2013.

Abstract

International audience; The functional and architectural benefits of embryonic stem cells (ESC) and myoblasts (Mb) transplantations into infarcted myocardium have been investigated extensively. Whereas ESC repopulated fibrotic areas and contributed to myocardial regeneration, Mb exerted their effects through paracrine secretions and scar remodeling. This therapeutic perspective, however, has been less explored in the setting of nonischemic dilated cardiomyopathies (DCMs). Our aim was to compare the integration and functional efficacy of ESC committed to cardiac fate by bone morphogenic protein 2 (BMP-2) pretreatment and Mb used as gold standard following their transplantation into the myocardium of a mouse model of laminopathy exhibiting a progressive and lethal DCM. After 4 and 8 weeks of transplantation, stabilization was observed in Mb-transplanted mice (P = 0.008) but not in groups of ESC-transplanted or medium-injected animals, where the left ventricular fractional shortening (LVFS) decreased by 32 ± 8% and 41 ± 8% respectively. Engrafted differentiated cells were consistently detected in myocardia of mice receiving Mb, whereas few or no cells were detected in the hearts of mice receiving ESC, except in two cases where teratomas were formed. These data suggest that committed ESC fail to integrate in DCM where scar tissue is absent to provide the appropriate niche, whereas the functional benefits of Mb transplantation might extend to nonischemic cardiomyopathy.

Details

Language :
English
ISSN :
15250016 and 15250024
Database :
OpenAIRE
Journal :
Molecular Therapy, Molecular Therapy, 2013, 21 (5), pp.1064-1075. ⟨10.1038/mt.2013.15⟩, Molecular Therapy; Vol 21
Accession number :
edsair.doi.dedup.....88b2073f97175454998d586d0f009265
Full Text :
https://doi.org/10.1038/mt.2013.15⟩