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Myoblasts and Embryonic Stem Cells Differentially Engraft in a Mouse Model of Genetic Dilated Cardiomyopathy
- 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.
- Subjects :
- Cardiomyopathy, Dilated
Male
Pathology
medicine.medical_specialty
Cellular differentiation
[SDV]Life Sciences [q-bio]
Cell- and Tissue-Based Therapy
030204 cardiovascular system & hematology
Biology
Muscle Development
Cell Line
Myoblasts
03 medical and health sciences
Paracrine signalling
Mice
0302 clinical medicine
Drug Discovery
Genetics
medicine
Myocyte
Animals
Molecular Biology
Embryonic Stem Cells
030304 developmental biology
Pharmacology
0303 health sciences
Regeneration (biology)
Myocardium
Graft Survival
Dilated cardiomyopathy
Cell Differentiation
Anatomy
medicine.disease
Embryonic stem cell
Myocardial Contraction
Transplantation
[SDV] Life Sciences [q-bio]
Disease Models, Animal
Phenotype
Cell culture
embryonic structures
Molecular Medicine
Female
Original Article
Subjects
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⟩