Article

Antioxidants improve early survival of cardiomyoblasts after transplantation to the myocardium.

Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA.
Molecular imaging and biology: MIB: the official publication of the Academy of Molecular Imaging (Impact Factor: 2.47). 12/2009; 12(3):325-34. DOI: 10.1007/s11307-009-0274-4
Source: PubMed

ABSTRACT We tested the hypothesis that modulation of the microenvironment (using antioxidants) will increase stem cell survival in hypoxia and after transplantation to the myocardium.
Rat cardiomyoblasts were stably transfected with a reporter gene (firefly luciferase) for bioluminescence imaging (BLI). First, we examined the role of oxidative stress in cells under hypoxic conditions. Subsequently, stem cells were transplanted to the myocardium of rats using high-resolution ultrasound, and their survival was monitored daily using BLI.
Under hypoxia, oxidative stress was increased together with decreased cell survival compared to control cells, both of which were preserved by antioxidants. In living subjects, oxidative stress blockade increased early cell survival after transplantation to the myocardium, compared to untreated cells/animals.
Modulation of the local microenvironment (with antioxidants) improves stem cell survival. Increased understanding of the interaction between stem cells and their microenvironment will be critical to advance the field of regenerative medicine.

0 Bookmarks
 · 
87 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cardiac stem cell therapy continues to hold promise for the treatment of ischemic heart disease despite the fact that early promising pre-clinical findings have yet to be translated into consistent clinical success. The latest human studies have collectively identified a pressing need to better understand stem cell behavior in humans and called for more incorporation of noninvasive imaging techniques into the design and evaluation of human stem cell therapy trials. This review discusses the various molecular imaging techniques validated to date for studying stem cells in living subjects, with a particular emphasis on their utilities in assessing the acute retention and the long-term survival of transplanted stem cells. These imaging techniques will be essential for advancing cardiac stem cell therapy by providing the means to both guide ongoing optimization and predict treatment response in humans.
    Trends in cardiovascular medicine 04/2013; · 4.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVE: Polycystic kidney disease (PKD) is a common cause of end stage renal failure and many of these patients suffer vascular dysfunction and hypertension. It remains unclear whether PKD is associated with abnormal microvascular structure. Thus, this study examined the renovascular structure in PKD. METHODS: PKD rats (PCK model) and controls were studied at 10 weeks of age, and mean arterial pressure (MAP), renal blood flow and creatinine clearance were measured. Microvascular architecture and cyst number and volume were assessed using micro-computed tomography, and angiogenic pathways evaluated. RESULTS: Compared to controls, PKD animals had an increase in MAP (126.4±4.0 vs. 126.2±2.7mmHg) and decreased clearance of creatinine (0.39±0.09 vs. 0.30±0.05ml/min), associated with a decrease in microvascular density, both in the cortex (256±22 vs. 136±20 vessels per cm(2) ) and medullar (114±14 vs. 50±9 vessels/cm(2) ) and an increase in the average diameter of glomeruli (104.14±2.94 vs. 125.76±9.06 mm). PKD animals had increased fibrosis (2.2±0.2 fold vs. control) and a decrease in the cortical expression in hypoxia inducible factor 1-α and vascular endothelial growth factor. CONCLUSION: PKD animals have impaired renal vascular architecture, which can have significant functional consequences. The PKD microvasculature could represent a therapeutic target to decrease the impact of this disease. © 2012 John Wiley & Sons Ltd.
    Microcirculation (New York, N.Y.: 1994) 11/2012; · 2.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVES: The goal of this study was to validate a pathway-specific reporter gene that could be used to noninvasively image the oxidative status of progenitor cells. BACKGROUND: In cell therapy studies, reporter gene imaging plays a valuable role in the assessment of cell fate in living subjects. After myocardial injury, noxious stimuli in the host tissue confer oxidative stress to transplanted cells that may influence their survival and reparative function. METHODS: Rat mesenchymal stromal cells (MSCs) were studied for phenotypic evidence of increased oxidative stress under in vitro stress. On the basis of their up-regulation of the pro-oxidant enzyme p67(phox) subunit of nicotinamide adenine dinucleotide phosphate (NAD[P]H oxidase p67(phox)), an oxidative stress sensor was constructed, comprising the firefly luciferase (Fluc) reporter gene driven by the NAD(P)H p67(phox) promoter. MSCs cotransfected with NAD(P)H p67(phox)-Fluc and a cell viability reporter gene (cytomegalovirus-Renilla luciferase) were studied under in vitro and in vivo pro-oxidant conditions. RESULTS: After in vitro validation of the sensor during low-serum culture, transfected MSCs were transplanted into a rat model of myocardial ischemia/reperfusion (IR) and monitored by using bioluminescence imaging. Compared with sham controls (no IR), cardiac Fluc intensity was significantly higher in IR rats (3.5-fold at 6 h, 2.6-fold at 24 h, 5.4-fold at 48 h; p < 0.01), indicating increased cellular oxidative stress. This finding was corroborated by ex vivo luminometry after correcting for Renilla luciferase activity as a measure of viable MSC number (Fluc:Renilla luciferase ratio 0.011 ± 0.003 for sham vs. 0.026 ± 0.004 for IR at 48 h; p < 0.05). Furthermore, in IR animals that received MSCs preconditioned with an antioxidant agent (tempol), Fluc signal was strongly attenuated, substantiating the specificity of the oxidative stress sensor. CONCLUSIONS: Pathway-specific reporter gene imaging allows assessment of changes in the oxidative status of MSCs after delivery to ischemic myocardium, providing a template to monitor key biological interactions between transplanted cells and their host environment in living subjects.
    JACC. Cardiovascular imaging 04/2013; · 14.29 Impact Factor

Full-text (2 Sources)

View
15 Downloads
Available from
May 16, 2014