title: Embryonic stem cell-based cardiopatches improve cardiac function in infarcted rats.
abstract: Pluripotent stem cell-seeded cardiopatches hold promise for in situ regeneration of infarcted hearts. Here, we describe a novel cardiopatch based on bone morphogenetic protein 2-primed cardiac-committed mouse embryonic stem cells, embedded into biodegradable fibrin matrices and engrafted onto infarcted rat hearts. For in vivo tracking of the engrafted cardiac-committed cells, superparamagnetic iron oxide nanoparticles were magnetofected into the cells, thus enabling detection and functional evaluation by high-resolution magnetic resonance imaging. Six weeks after transplantation into infarcted rat hearts, both local (p < .04) and global (p < .015) heart function, as well as the left ventricular dilation (p < .0011), were significantly improved (p < .001) as compared with hearts receiving cardiopatches loaded with iron nanoparticles alone. Histological analysis revealed that the fibrin scaffolds had degraded over time and clusters of myocyte enhancer factor 2-positive cardiac-committed cells had colonized most of the infarcted myocardium, including the fibrotic area. De novo CD31-positive blood vessels were formed in the vicinity of the transplanted cardiopatch. Altogether, our data provide evidence that stem cell-based cardiopatches represent a promising therapeutic strategy to achieve efficient cell implantation and improved global and regional cardiac function after myocardial infarction.
authors.affiliation: Department of Radiology, Geneva University Hospitals and University of Geneva, Switzerland.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Vallée
authors.forename: Mathieu
authors.initials: M
authors.lastname: Hauwel
authors.forename: Matthieu
authors.initials: M
authors.lastname: Lepetit-Coiffé
authors.forename: Wang
authors.initials: W
authors.lastname: Bei
authors.forename: Karin
authors.initials: K
authors.lastname: Montet-Abou
authors.forename: Paolo
authors.initials: P
authors.lastname: Meda
authors.forename: Stephany
authors.initials: S
authors.lastname: Gardier
authors.forename: Prisca
authors.initials: P
authors.lastname: Zammaretti
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Kraehenbuehl
authors.forename: Francois
authors.initials: F
authors.lastname: Herrmann
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Hubbell
authors.forename: Marisa E
authors.initials: ME
authors.lastname: Jaconi
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000502:physiology; D006321:Heart / Q000502:physiology*; D007124:Immunoenzyme Techniques; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D009203:Myocardial Infarction / Q000628:therapy*; D051381:Rats; D033581:Stem Cell Transplantation