Rationale: Although mesenchymal stem cell (MSC) transplantation has been shown to promote cardiac repair in acute myocardial injury in vivo, its overall restorative capacity appears to be restricted mainly because of poor cell viability and low engraftment in the ischemic myocardium. Specific chemokines are upregulated in the infarcted myocardium. However the expression levels of the corresponding chemokine receptors (eg, CCR1, CXCR2) in MSCs are very low. We hypothesized that this discordance may account for the poor MSC engraftment and survival. Objective: To determine whether overexpression of CCR1 or CXCR2 chemokine receptors in MSCs augments their cell survival, migration and engraftment after injection in the infarcted myocardium. ver the past few years adult stromal mesenchymal stem cells have been extensively investigated for their potential in developing cell based therapies for the treatment of cardiac injury and/or other regenerative diseases. 1,2 Numerous studies have shown that transplantation of those cells in postinfarct mice decreased mortality, reduced infarct size and improved cardiac function. 2 More recently, preliminary data from a clinical study of MSCs in 69 postinfarct patients also demonstrated improved left ventricular function. 3 Despite the progress, many barriers for translating the promise of stem cell therapy into practice still exist. Homing, engraftment and survival of the transplanted cells in the ischemic area still pose major problems, with most of the cells being lost within hours of the transplantation. Moreover, the mechanisms determining these processes are still not well understood. Methods and Results: Overexpression of CCR1, but not CXCR2, dramatically increased chemokine-induced murine MSC migration and protected MSC from apoptosis in vitro. Moreover, when MSCs were injected intramyocardially one hour after coronary artery ligation, CCR1-MSCs accumulated in the infarcted myocardium at significantly higher levels than control-MSCs or CXCR2-MSCs 3 days postmyocardial infarction (MI). CCR1-MSC-injected hearts exhibited a significant reduction in infarct size, reduced cardiomyocytes apoptosis and increased capillary density in injured myocardiumChemokine induction is one of the prominent features in the postischemic heart associated with neutrophil infiltration and potential angiogenic effects. 4 Importantly, various chemokine/chemokine receptor axes are essential and potent regulators of chemotactic activities for a wide range of cell types such as monocytes and stem cells. We and others have demonstrated that many chemokines, including chemokine (c-c motif) ligand 7 (CCL7), chemokine (c-x-c motif) ligand 1 (CXCL1), chemokine (c-x-c motif) ligand 2 (CXCL2), and others were significantly upregulated in the heart following myocardial infarction (MI) and might be implicated in regulating engraftment and homing of MSCs to infarcted myocardium. [5][6][7] Although functionally active receptors for those chemokines have been identified in MSCs, their respective expression lev...

Unique spectral properties of quantum dots (QDs) enable ultrasensitive and long-term biolabeling. Aiming to trace the infection, movement, and localization of viruses in living cells, QD-containing virus-like particles (VLPs) of simian virus 40 (SV40), termed SVLP-QDs, are constructed by in vitro self-assembly of the major capsid protein of SV40. SVLP-QDs show homogeneity in size ( approximately 24 nm), similarity in spectral properties to unencapsidated QDs, and considerable stability. When incubated with living cells, SVLP-QDs are shown to enter the cells by caveolar endocytosis, travel along the microtubules, and accumulate in the endoplasmic reticulum. This process mimics the early infection steps of SV40. This is the first paradigm of imaging viral behaviors with encapsidated QDs in living cells. The method may provide a new alternative for various purposes, such as tracing viruses or viral components, targeted nanoparticle delivery, and probing of drug delivery.

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