Cell therapy in myocardial infarction: emphasis on the role of MRI

Abstract

Despite tremendous progress in myocardial infarct (MI) treatment, mortality rates remain substantial. Permanent loss of cardiomyocytes after ischemic injury, results in irreversible loss of myocardial contractility, reduction in ventricular performance, and may initiate the development of dilated heart failure. The discovery that pluripotent progenitor cells bear the capacity to differentiate to mature cardiac cells raised the hope of cell-based regenerative medicine. Engraftment of stem cells in the damaged myocardium, repair and functional improvement appeared suddenly a nearby reality. Promising results in animal models, and preliminary studies reporting the feasibility and safety of adult stem cell therapy in MI patients led to the first double-blinded randomized, placebo-controlled trials. The initial great enthusiasm for this paradigm shift in MI treatment has been tempered by the mainly negative or modestly positive study findings. Before new, larger clinical trials can be initiated, a number of critical questions and issues need to be considered starting with a scrutinized analysis of currently available data to extending our knowledge of the mechanism of scarless myocardial regeneration. Cardiac cell therapy necessitates a multidisciplinary approach, whereby imaging, in particular MRI, and the input of the imaging specialist is crucial to the success of cardiac cell regenerative medicine. MRI is an appealing technique for cell trafficking depicting engraftment, differentiation and survival. Endomyocardial cell administration can be achieved safely with MR fluoroscopy and MRI is without any doubt the most accurate and reproducible technique to measure study end-points.

Emerging roles for integrated imaging modalities in cardiovascular cell-based therapeutics: a clinical perspective

“…With physical and chemical modifications, several generations of MNP have now been synthesised. Early generation MNP comprised superparamagnetic iron oxide particles (SPIO, 60–150 nm in diameter), such as the ferumoxide, Feridex (Advanced Magnetics, Cambridge, MA, USA) and micron-sized iron oxide particles (MPIO, 0.7–1.6 µm) [70]. SPIO contain relatively thin dextran coats and tend to form polycrystalline clusters, allowing their rapid clearance from the circulation by the reticuloendothelial system.…”

“…It is therefore highly desirable for investigators to have access to objective, operator-independent modalities that can provide accurate and reproducible quantification of global ejection fraction, especially in the presence of LV dilatation and dysfunction [138]. To this end, a large number of clinical trials have favoured the use of MRI [70], as well as radionuclide angiography (gated blood pool scan), SPECT and PET over standard echocardiography or LV cineangiography. In the setting of established ischaemic cardiomyopathy, well-established PET or MRI techniques can also be used to distinguish hibernating myocardium from non-viable, post-infarct scar in order to shed light on the underlying cause of ischaemic dysfunction.…”

Emerging MRI Methods in Translational Cardiovascular Research

“…Limitations of gadolinium agents include lower sensitivity and the potential for alterations in proliferation and gene expression amongst certain cell types [95]. For these reasons, cell labeling with iron oxide particles has been more common amongst MRI cell tracking studies [92, 96] [97, 98]. Recent studies have used MRI cell tracking with iron oxide particles and T2* weighted imaging to track both embryonic stem cells [99] (Figure 9) and bone marrow stromal cells [100] after implantation into the infarcted rat heart, to label and track macrophages in a mouse model of MI [101], and to track cells involved in heart transplant rejection in a rat model [102].…”

Polycationic Nanoparticles: (1) Synthesis of a Polylysine-MION Conjugate and its Application in Labeling Fibroblasts

“…MRI provides valuable real time cell tracking information in regenerative medicine [15][16][17]. Recent interest, accordingly, has focused on developing ex vivo cell labeling methods using MION and other ultrasmall superparamagnetic iron oxide nanoparticle contrast agents (USPIO) for analytic uses in development of cell therapy technology.…”