title: Myoblasts and embryonic stem cells differentially engraft in a mouse model of genetic dilated cardiomyopathy.
abstract: 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.
authors: UPMC UM 76, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
authors: Cyril
authors: C
authors: Catelain
authors: Stéphanie
authors: S
authors: Riveron
authors: Aurélie
authors: A
authors: Papadopoulos
authors: Nathalie
authors: N
authors: Mougenot
authors: Adeline
authors: A
authors: Jacquet
authors: Karine
authors: K
authors: Vauchez
authors: Erica
authors: E
authors: Yada
authors: Michel
authors: M
authors: Pucéat
authors: Marc
authors: M
authors: Fiszman
authors: Gillian
authors: G
authors: Butler-Browne
authors: Gisèle
authors: G
authors: Bonne
authors: Jean-Thomas
authors: JT
authors: Vilquin
mesh_terms: D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D002454:Cell Differentiation; D002460:Cell Line; D064987:Cell- and Tissue-Based Therapy; D004195:Disease Models, Animal; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D005260:Female; D006085:Graft Survival; D008297:Male; D051379:Mice; D024510:Muscle Development; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010641:Phenotype