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 cardiaccommitted 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. STEM CELLS TRANSLATIONAL MEDICINE 2012;1:248 -260

Magnetic Resonance Imaging of Cardiac Strain Pattern Following Transplantation of Human Tissue Engineered Heart Muscles

“…Although some studies have utilized strain imaging from both tagged MRI and cardiac ultrasound to assess therapeutic efficacy, 29–31 its detection limits and limits of agreement for these localized regenerative therapies have not been evaluated. To fill this gap, we validated strain analysis by using 3D tagged MRI and 2D ultrasound imaging data from infarcted rat hearts before and after EHM transplantations or sham surgery (control).…”

Harmonic Nanoparticles for Regenerative Research

“…The approach described in this protocol is limited to optical tracking and, although the possibility of using infrared excitation leads to increased penetration depth with respect to fluorescence based techniques; optical imaging cannot be extended to whole body and therefore should be complemented by magnetic detection 21 . Previous published work showed several approaches to assess structure and movement of cardiac cell clusters, including labeling by fluorescent dyes 22 , quantum dots 23,24 , super-paramagnetic iron oxide nanoparticles 25 , and up-conversion fluorescent particles [26][27][28] . The advantages of HNPs with respect to these nanoprobes are associated with absence of bleaching over extended periods of time, increased imaging penetration, wavelength tunability for increased contrast with respect to autofluorescence.…”

Polymeric Scaffold Aided Stem Cell Therapeutics for Cardiac Muscle Repair and Regeneration

“…PEGylated 15 nm gold nanoparticles grafted within the poly(methylglutarimide) (PMGI) nanofibers along with adhesion peptides RGD and HBP (heparin binding protein) induced the differentiation of pluripotent stem cells to cardiomyocytes . Superparamagnetic iron oxide (SPIO) nanoparticles, when transfected within the ESC pretreated into the cardiac induction medium . These cells were loaded in a fibrin matrigel and injected to ischemic scar tissue of rat AMI model.…”

“…These cells were loaded in a fibrin matrigel and injected to ischemic scar tissue of rat AMI model. High‐resolution MRI studies revealed heart function after six weeks due to ESC commitment to cardiac lineage in fibrin matrix . Martinelli et al showed neonatal cardiomyocytes interact with multiwalled carbon nanotubes (MWCNT) forming desmosome mediated tight junctions, which helps in the rapid proliferation and differentiation to mature cardiomyocyte.…”