Monitoring of rSO could be considered as an interesting tool to monitor the brain of patients on VA-ECMO.
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 cm2) and medullar (114±14 vs. 50±9 vessels/cm2) 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.
Objectives We aimed 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 upregulation of the pro-oxidant enzyme NAD(P)H oxidase p67phox, an oxidative stress sensor was constructed, comprising the firefly luciferase (Fluc) reporter gene driven by the NAD(P)H p67phox promoter. MSCs co-transfected with NAD(P)H p67phox-Fluc and a cell viability reporter gene (CMV-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 bioluminescence imaging. Compared to 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 was corroborated by ex vivo luminometry after correcting for renilla luciferase (Rluc) activity as a measure of viable MSC number (Fluc:Rluc ratio 0.011 ± 0.003 for sham versus 0.026 ± 0.004 for IR at 48 h, P<0.05). Furthermore, in IR animals that received MSCs preconditioned with an anti-oxidant 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.
Objectives This study sought to evaluate adventitial vasa vasorum (VV) in vivo with novel imaging technique of optical coherence tomography (OCT). Methods To verify OCT methods for quantification of VV, we first studied 2 swine carotid arteries in a model of focal angiogenesis by autologous blood injection, and compared microchannel volume (MCV) by OCT and VV by m-CT, and counts of those. In OCT images, adventitial MC was identified as signal-voiding areas which were located within 1 mm from the lumen-intima border. After manually tracing microchannel areas and the boundaries of lumen-intima and media-adventitial in all slices, we reconstructed 3D images. Moreover, we performed with OCT imaging in 8 recipients referred for evaluation of cardiac allograft vasculopathy at 1 year after heart transplantation. MCV and plaque volume (PV) were assessed with 3D images in each 10-mm-segment. Results In the animal study, among the 16 corresponding 1-mm-segments, there were significant correlations of count and volume between both the modalities (count r2=0.80, P<0.01; volume r2 =0.50, P<0.01) and a good agreement with a systemic bias toward underestimation with m-CT. In the human study, there was a significant positive correlation between MCV and PV (segment number=24, r2 =0.63, P<0.01). Conclusion Our results suggest that evaluation of MCV with 3D OCT imaging might be a novel method to estimate the amount of adventitial VV in vivo, and further has the potential to provide a pathophysiological insight into a role of the VV in allograft vasculopathy.
Polycystic kidney disease (PKD) is a common cause of end stage renal failure, for which there is no accepted treatment. Progenitor and stem cells have been shown to restore renal function in a model of renovascular disease, a disease that shares many features with PKD. The objective of this study was to examine the potential of adult stem cells to restore renal structure and function in PKD. Bone marrow-derived mesenchymal stromal cells (MSCs, 2.5×105) were intrarenally infused in 6 week-old PCK rats. At 10 weeks of age, PCK rats had an increase in systolic blood pressure (SBP) vs. controls (126.22±2.74 vs. 116.45±3.53mmHg, p<0.05) and decreased creatinine clearance (3.76±0.31 vs. 6.10±0.48µl/min/g, p<0.01), which were improved in animals that received MSCs (SBP: 114.67±1.34mmHg, and creatinine clearance: 4.82±0.24µl/min/g, p=0.001 and p=0.003 vs. PKD, respectively). MSCs preserved vascular density and glomeruli diameter, measured using micro-computed tomography. PCK animals had increased urine osmolality (843.9±54.95 vs. 605.6±45.34mOsm, p<0.01 vs. control), which was improved after MSC infusion and not different from control (723.75±56.6mOsm, p=0.13 vs. control). Furthermore, MSCs reduced fibrosis and preserved the expression of the pro-angiogenic molecules, while cyst size and number were unaltered by MSCs. Delivery of exogenous MSCs improved vascular density and renal function in PCK animals, and the benefit was observed up to four weeks after a single infusion. Cell-based therapy constitutes a novel approach in PKD.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.