STEMCELLTRACK · Assessment of Global and Regional Cardiac Functional Improvements in a Murine Model of Myocardial Infarction following Stem Cell Treatments

Assessment of Global and Regional Cardiac Functional Improvements in a Murine Model of Myocardial Infarction following Stem Cell Treatments

Cardiac progenitor stem cell (CPC) therapy for myocardial infarction (MI) has been shown to elicit moderate beneficial effects. Research currently focuses on improving CPC administration, retention, and efficacy. The conducted project work achieved the development of Magnetic Resonance Imaging (MRI) and engineering tools to facilitate this research in normal mice. Intra-cardiac injections of CPCs labeled with perflurocrown-ether (PFCE) nanoparticles (NPs) and with the highly efficient transfection agent FuGENE can be visualized and tracked for the first time with 19F MRI in mice for approximately 8 days. The primary mechanisms attributing cellular status and temporal signal changes have been investigated, and have been shown to include (among others) possible: a) CPC migration/dispersion, b) cell death, and c) macrophage infiltration and scavenging. Furthermore, the developed methodologies achieved in vivo cardiac 19F MRI of injected labeled CPCs by reducing imaging acquisition to a few minutes, providing evidence for their potential for possible translational work. Parallel to these studies there was an independent design, synthesis, use, and evaluation of a polymeric scaffolds. Overall, we have shown that porous, medium-chain length poly-caprolactone/poly(3-hydroxyoctanoate) polymer blends have superior performance in terms of the seeding density, adhesion, and CPC viability/proliferation. The choice of this material underlines one of the important novelties of pursued work, given its elastomeric nature, mechanical properties, and its potential to be conjugated with vascular growth factors and peptides to further prolong cellular attachment, viability, and proliferation. Its structural advantages/morphological characteristics are tunable and allow maximization of the seeding density for faster detection and temporal follow-up using direct, 19F MRI/MRS in vivo for at least 9 days post-implantation, as documented in mice. Through a personalized career development plan, the fellowship allowed training of the researcher in advanced cellular characterization, synthesis, labeling, and bio-imaging techniques, synergistically with trans-European mobility through two secondments, reinforcing his scientific and managerial qualities.

Data: CORDIS, © European Union