ArticleJACC. Cardiovascular imaging2013
Noninvasive monitoring of oxidative stress in transplanted mesenchymal stromal cells.
Article in JACC. Cardiovascular imaging, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 31 citations in OpenAlex.
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- Biophysical methods for quality evaluation of decellularized and recellularized tissue-engineered constructs of organs and tissues.Journal of biosciences · 2019Article
- Estimation of Decellularization and Recellularization Quality of Tissue-Engineered Constructions by the Chemiluminescence Method.Doklady. Biochemistry and biophysics · 2019Article
- The Transcription Factor Nrf2 Protects Angiogenic Capacity of Endothelial Colony-Forming Cells in High-Oxygen Radical Stress Conditions.Stem cells international · 2017Article
- Noninvasive Assessment of Cell Fate and Biology in Transplanted Mesenchymal Stem Cells.Methods in molecular biology (Clifton, N.J.) · 2017Article
- Noninvasive Monitoring of the Mitochondrial Function in Mesenchymal Stromal Cells.Molecular imaging and biology · 2016Article
- Mesenchymal Stromal Cells Improve Renovascular Function in Polycystic Kidney Disease.Cell transplantation · 2015Article
- Modulation of the maladaptive stress response to manage diseases of protein folding.PLoS biology · 2014Article
- An update on stem cell therapies for acute coronary syndrome.Current cardiology reports · 2014Review
- Renin inhibition improves the survival of mesenchymal stromal cells in a mouse model of myocardial infarction.Journal of cardiovascular translational research · 2014Article
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10 authors at 3 institutions in 1 country.
Funding
Abstract
objectivesThe 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.
backgroundIn 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.
methodsRat 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.
resultsAfter 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.
conclusionsPathway-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.
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