Magnetic Nanoparticles for Targeting and Imaging of Stem Cells in Myocardial Infarction

Abstract

Stem cell therapy has broad applications in regenerative medicine and increasingly within cardiovascular disease. Stem cells have emerged as a leading therapeutic option for many diseases and have broad applications in regenerative medicine. Injuries to the heart are often permanent due to the limited proliferation and self-healing capability of cardiomyocytes; as such, stem cell therapy has become increasingly important in the treatment of cardiovascular diseases. Despite extensive efforts to optimize cardiac stem cell therapy, challenges remain in the delivery and monitoring of cells injected into the myocardium. Other fields have successively used nanoscience and nanotechnology for a multitude of biomedical applications, including drug delivery, targeted imaging, hyperthermia, and tissue repair. In particular, superparamagnetic iron oxide nanoparticles (SPIONs) have been widely employed for molecular and cellular imaging. In this mini-review, we focus on the application of superparamagnetic iron oxide nanoparticles in targeting and monitoring of stem cells for the treatment of myocardial infarctions.

Figure 1

Schematic representation of cell labeling and imaging modalities (reproduced with permission [25]).

Figure 2

In vivo visualization immediately before and after IFP-MSC injection. Long-axis SSFP MRI view of left ventricle before (a) and after (b) transcatheter injection of 4 × 106 IFP-labeled MSCs into the infarct at the apex (arrows) and adjoining normal myocardium (arrowhead). Delayed enhancement MRI highlights areas of nonviable infarcted myocardium using the same view as above, before (c) and after (d) injection of IFP-labeled MSCs. MSCs appear dark against hyperenhanced infarct (reproduced with permission [27]).

Figure 3

Schematic representation of generation and clearance of SPIONs in the myocardium (reproduced with permission [34]).

Figure 4

(a) Representative BLI images of the mice injected with Magnelle and Molday ION labeled reporter gene-transduced iCMs or PBS alone as control, after days 7 and 14 of cell injections (top) and their corresponding in vivo MRI images of the murine hearts (bottom); red arrows show the signal from the injected labeled cells. (b) Representative BLI images of the selected mice with dead cardiomyocytes (after day 14 of Magnelle labeled cells) and the corresponding in vivo MRI images.

Figure 5

Schematic representation of MRI reporter genes used for cell labeling, reproduced with permission from reference [40].

Figure 6

Mechanism of genetic manipulation of ESCs. HA, myc, and FLUC genes integrated into (a) the genome of ESCs and (b) coexpressed on the cell surface. SPIO conjugated monoclonal antibody specifically targets the antigens expressed on the cell surface, reproduced with permission from reference [42].

Figure 7

(a) Prussian blue staining showing the proper labeling of rat CDCs with ferumoxytol (FHB), (b) serum cardiac troponin-I (sTnI) values after intracoronary injection of 500,000 cells into noninfarcted rats, (c) T2^∗ weighted MRI images showing higher cell retention in magnetic targeted samples (according to their dark signals which are shown by red arrows) 24 h after delivery of CDCs into rats myocardial infarcted model, (d) fluorescent imaging demonstrating the existence of labelled cells (in red, as the cells were transduced by red fluorescent protein) in rat in hearts and lungs, and (e) SRY qPCR quantitation of cell retention (reproduced with permission [44]). ∗ indicates statistical significance with p < 0.05.