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ABSTRACT: Adipose tissue stromal fraction (ASF) contains multipotent cells capable of differentiation towards several lineages and may be used for the treatment of various degenerative diseases. However, the multipotent cells within ASF have not been fully characterized. In this study we have attempted to characterize stem cells in the ASF obtained through serial dilution. Five single-cell clones were studied. It was found that the single-cell clones exhibited slight but significant differences in proliferative capacity and differentiation potential. We conclude that ASF houses different subtypes of stem cells.
Canadian Journal of Physiology and Pharmacology 08/2012; 90(9):1295-301. · 1.95 Impact Factor
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Hung-Yu Lin, Darren Freed,
Trevor W R Lee,
Rakesh C Arora,
Ayyaz Ali,
Waiel Almoustadi,
Bo Xiang,
Fei Wang,
Stephen Large,
Scott B King,
Boguslaw Tomanek,
Ganghong Tian
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ABSTRACT: To validate noninvasive cardiac output measurements of phase-contrast magnetic resonance imaging (PC-MRI) and cine MRI using an invasive pressure-volume (PV) loop technique on a swine model.
We compared three methods for evaluating cardiac function at rest and under pharmaceutical low-dose inotropic infusion conditions: 1) phase-contrast MRI, 2) cine MRI, and 3) PV loop relationship. These measurements were made in 14 domestic pigs under rest conditions. Identical MRI acquisitions and PV loop analysis were performed on six pigs from the same group that received an infusion of dobutamine 2.5 μg/kg/min. Cardiac outputs from all measurements were analyzed and compared using linear regression and Bland-Altman analysis.
Noninvasive PC-MRI and cine MRI did not show any significant differences compared to an invasive PV loop technique for measurement of cardiac output under both rest (PC-MRI, cine MRI, and PV loop, 3.17 ± 0.45, 3.18 ± 0.61, 3.45 ± 0.41 L/min, respectively) and pharmaceutical low-dose inotropic infusion conditions (PC-MRI, cine MRI, and PV loop, 4.78 ± 0.53, 4.7 ± 0.6, 4.96 ± 0.48 L/min, respectively). Statistical analysis showed good agreement of cardiac output measurements at rest (R(2) = 0.83) and under low-dose inotropic infusion conditions (R(2) = 0.74) using PC-MRI and PV loop techniques. Cardiac output measurement using cine MRI and PV loop techniques also showed good agreement at rest (R(2) = 0.85) and under low-dose inotropic infusion conditions (R(2) = 0.76). Furthermore, cardiac outputs determined with the three modalities showed good agreement over a wide range of heart rates (90-180 bpm).
MRI can provide a reliable, noninvasive measurement of cardiac output that can be carried out without the complications that are inherent with current invasive procedures.
Journal of Magnetic Resonance Imaging 07/2011; 34(1):203-10. · 2.70 Impact Factor
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ABSTRACT: Adipose-derived stem cells (ASCs) have promising potential in regenerative medicine and cell therapy. Our objective is to examine the biological function of the labeled stem cells following labeling with a readily available positron emission tomography (PET) tracer, (18)F-fluoro-2-deoxy-D: -glucose (FDG). In this work we characterize labeling efficiency through assessment of FDG uptake and retention by the ASCs and the effect of FDG on cell viability, proliferation, transdifferentiation, and cell function in vitro using rat ASCs.
Samples of 10(5) ASCs (from visceral fat tissue) were labeled with concentrations of FDG (1-55 Bq/cell) in 0.75 ml culture medium. Label uptake and retention, as a function of labeling time, FDG concentration, and efflux period were measured to determine optimum cell labeling conditions. Cell viability, proliferation, DNA structure damage, cell differentiation, and other cell functions were examined. Non-labeled ASC samples were used as a control for all experimental groups. Labeled ASCs were injected via tail vein in several healthy rats and initial cell biodistribution was assessed.
Our results showed that FDG uptake and retention by the stem cells did not depend on FDG concentration but on labeling and efflux periods and glucose content of the labeling and efflux media. Cell viability, transdifferentiation, and cell function were not greatly affected. DNA damage due to FDG radioactivity was acute, but reversible; cells managed to repair the damage and continue with cell cycles. Over all, FDG (up to 25 Bq/cell) did not impose severe cytotoxicity in rat ASCs. Initial biodistribution of the FDG-labeled ASCs was 80% + retention in the lungs. In the delayed whole-body images (2-3 h postinjection) there was some activity distribution resembling typical FDG uptake patterns.
For in vivo cell tracking studies with PET tracers, the parameter of interest is the amount of radiotracer that is present in the cells being labeled and consequent biological effects. From our study we developed a labeling protocol for labeling ASCs with a readily available PET tracer, FDG. Our results indicate that ASCs can be safely labeled with FDG concentration up to 25 Bq/cell, without compromising their biological function. A labeling period of 90 min in glucose-free medium and efflux of 60 min in complete media resulted in optimum label retention, i.e., 60% + by the stem cells. The initial biodistribution of the implanted FDG-labeled stem cells can be monitored using microPET imaging.
European Journal of Nuclear Medicine 03/2011; 38(7):1323-34. · 4.53 Impact Factor
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ABSTRACT: Most deaths in the first 30 days after cardiac transplantation are due to failure of the donor heart, often with the clinical picture of right ventricular failure. Indeed, there is a significant reduction in contractility of the human donor heart and loss of contractile reserve before and soon after transplantation. This myocardial insult appears in association with brain death in the donor and follows a "catecholamine storm" associated with a rapidly rising intracranial pressure. Microscopy of the myocardium in organ donors shows a picture typical of catecholamine-induced injury and similar to changes found in endomyocardial specimens of stress cardiomyopathy (catecholamine-induced cardiomyopathy, or Takotsubo cardiomyopathy). There are 3 common features between stress cardiomyopathy and the heart of a brain-dead donor: exposure of the heart to unusually high catecholamine levels, ventricular dysfunction, and prompt recovery. Stress cardiomyopathy is a temporary myocardial dysfunction that has been described after sub-arachnoid hemorrhage, traumatic head injury, pheochromocytoma, acute emotional distress, exogenous administration of catecholamines, and non-related surgery. Given the common features of this catecholamine-mediated myocardial insult, we ask if brain-dead donor heart dysfunction is an extreme variant of stress cardiomyopathy? And, if so is it, like stress cardiomyopathy, reversible? Can we therefore expect recovery of the dysfunctional donor heart over time, thereby permitting increased use of hearts offered for transplantation?
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 09/2010; 29(9):957-65. · 3.54 Impact Factor
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ABSTRACT: Recurrent angina refractory to medical therapy in patients having undergone prior coronary artery bypass grafting (CABG) is an indication for repeat surgical revascularisation. The primary aim of this retrospective study was to determine the benefit of redo surgery over the longer term with regards to survival and freedom from cardiac symptoms/events. Our secondary aim was to identify risk factors that compromise surgical efficacy of redo revascularisation.
Patients were identified through case note review. Survivors were interviewed by telephone according to a defined protocol. Actuarial freedom from cardiac symptoms/events and survival were determined. A composite outcome for cardiac symptoms/events was used and defined as angina class> or =2 or NYHA> or =2 or myocardial infarction or need for percutaneous intervention. Univariate and multivariate analysis was performed. Survival was assessed using a Kaplan-Meier method, and determinants of survival with the Cox proportional hazards model.
Between January 1st, 1996 and February 1st, 2004, 101 consecutive patients underwent redo CABG at our institution under the care of a single surgeon. There were 91 men and 10 women, 64% (65/101) had an age> or =70 years. 30-Day mortality was 1.2% (2/101). Mean time to follow-up was 5.3+/-3.8 years. Poor left ventricular function and pre-operative NYHA> or =2 status were independent predictors of decreased survival with hazard ratios (HR) of 2.12 (1.042-4.31) and 3.98 (1.39-11.39) respectively. The use of a radial artery graft at re-operation was an independent predictor of peri-operative death OR=18 (1-346). Actuarial survival at 1, 5 and 8 years was 90.1%, 84.4% and 76.9% and freedom from cardiac symptoms/events was 100%, 95% and 68% respectively.
This study shows acceptable short- and long-term survival and freedom from symptoms/events in patients undergoing redo coronary artery bypass grafting at a single institution. The apparent association between radial arterial grafts and impaired early clinical outcome warrants further investigation.
Heart Lung & Circulation 04/2010; 19(9):528-34. · 1.20 Impact Factor
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ABSTRACT: A bicuspid aortic valve (BAV) may be associated with an aortopathy affecting clinical outcome. Our aim was to assess long-term outcome and analyse if progressive aortic dilatation occurs with time in patients with BAV disease who underwent stentless valve replacement.
Demographic, operative and clinical data were retrospectively reviewed. Patients were classified according to whether their native aortic valve was identified as tricuspid (TC) or bicuspid (BC) at the time of AVR. Serial transthoracic echocardiography was used to measure changes in ascending aortic diameter over time. Propensity adjustment and multivariate regression were used. Events over time were assessed using the Kaplan-Meier method, and the determinants of events were assessed with the Cox proportional-hazards model.
Between January 1991 and January 2001, 215 patients underwent AVR. They had a serial follow-up echocardiography performed for a mean of 6.1+/-4.3 years postoperatively. Ninety patients (41%) had a BAV, and the BC group was younger (BC 62+/-15 years vs TC 71+/-12 years; p=0.002). We found no difference in the increase in ascending aortic diameter over follow-up (BC 0.1+/-0.5 cm vs TC 0.0+/-0.5 cm; p=0.34). BC morphology was not an independent predictor of increased overall mortality (propensity-adjusted hazard ratio: 0.79; 95% confidence interval (CI): 0.42-1.44; p=0.44) or increased risk of reoperation (propensity adjusted hazard ration: 1.84; 95% CI: 0.88-3.36; p=0.11).
Stentless AVR is protective against progressive aortic aneurysmal disease and confers excellent clinical outcomes in patients with BAV and normal preoperative ascending aortic diameter.
European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 03/2010; 38(2):134-40. · 2.40 Impact Factor
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ABSTRACT: The xenograft stentless valve was designed to emulate the haemodynamic performance of the allograft. Early outcomes using either surgical option (stentless xenograft valve or allograft) have been similar. However, follow-up outcomes remain to be compared. Between 1st January 1991 and 1st January 2001, 415 patients underwent aortic valve replacement. Two hundred and seventeen patients received an allograft and in 198 patients a Toronto stentless porcine valve (TSPV) was implanted. Mean time to follow-up was 6.3+/-4.4 years. Ten years freedom from structural valve deterioration (SVD) (TSPV 86+/-5%, allograft 82+/-5%, P=0.49) and freedom from reoperation (RE) (TSPV 80+/-4% vs. allograft 85+/-4%, P=0.61) were not significantly different. The TSPV was associated with significantly worse actuarial survival than the homograft (TSPV 40+/-4% vs. homograft 55+/-4%, P=0.02). However, after adjustment for other variables using a multivariate model, TSPV use was not an independent predictor of impaired late survival (LS) (P=0.44). Kaplan-Meier analysis in a subgroup of patients aged 45-65 years comparing LS, RE and SVD between xenografts and allografts identified similar results. The porcine stentless valve may be associated with similar clinical performance to the allograft over the medium to long-term.
Interactive cardiovascular and thoracic surgery 03/2010; 11(2):166-70.
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Lei Wang,
Jixian Deng,
Weichen Tian,
Bo Xiang,
Tonghua Yang,
Gang Li,
Jian Wang,
Marco Gruwel,
Tarek Kashour,
John Rendell,
Miriam Glogowski,
Boguslaw Tomanek, Darren Freed,
Roxanne Deslauriers,
Rakesh C Arora,
Ganghong Tian
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ABSTRACT: This study assessed the potential therapeutic efficacy of adipose-derived stem cells (ASCs) on infarcted hearts. Myocardial infarction was induced in rat hearts by occlusion of the left anterior descending artery (LAD). One week after LAD occlusion, the rats were divided into three groups and subjected to transplantation of ASCs or transplantation of cell culture medium (CCM) or remained untreated. During a 1-mo recovery period, magnetic resonance imaging showed that the ASC-treated hearts had a significantly greater left ventricular (LV) ejection fraction and LV wall thickening than did the CCM-treated and untreated hearts. The capillary density in infarct border zone was significantly higher in the ASC-treated hearts than in the CCM-treated and untreated hearts. However, only 0.5% of the ASCs recovered from the ASC-treated hearts were stained positive for cardiac-specific fibril proteins. It was also found that ASCs under a normal culture condition secreted three cardiac protective growth factors: vascular endothelial growth factor, hepatocyte growth factor, and insulin-like growth factor-1. Results of this study suggest that ASCs were able to improve cardiac function of infarcted rat hearts. Paracrine effect may be the mechanism underlying the improved cardiac function and increased capillary density.
AJP Heart and Circulatory Physiology 08/2009; 297(3):H1020-31. · 3.71 Impact Factor
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Lei Wang,
Jixian Deng,
Jian Wang,
Bo Xiang,
Tonghua Yang,
Marco Gruwel,
Tarek Kashour,
Boguslaw Tomanek,
Randy Summer, Darren Freed,
Davinder S Jassal,
Guangping Dai,
Miriam Glogowski,
Roxanne Deslauriers,
Rakesh C Arora,
Ganghong Tian
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ABSTRACT: The objectives of this study were (1) to determine whether superparamagnetic iron oxide (SPIO) affects viability, transdifferentiation potential and cell-factor secretion of adipose-derived stem cells (ASCs); and (2) to determine whether SPIO-enhanced magnetic resonance (MR) imaging highlights living stem cells. Rat ASCs were incubated in SPIO-containing cell culture medium for 2 days. The SPIO-treated ASCs were then subjected to adipogenic, osteogenic and myogenic transdifferentiation. Expression of vascular endothelial growth factor, hepatocyte growth factor and insulin-like growth factor 1 by the SPIO-treated ASCs was measured using reverse transcription polymerase chain reaction. Cell viability was assessed using trypan blue stain. For in vivo experiments, SPIO-labeled ASCs were injected into 10 rat hearts. The hearts were monitored using MRI. We found that survival rate of the ASCs cultured in the SPIO-containing medium was very high (97-99%). The SPIO-treated ASCs continued to express specific markers for the three types of transdifferentiation. Expression of the cell factors by the ASCs was not affected by SPIO. Signal voids on MR images were associated with the living SPIO-labeled ASCs in the rat hearts. We conclude that SPIO does not affect viability, transdifferentiation potential or cell-factor secretion of ASCs. MRI mainly highlights living SPIO-labeled stem cells.
Magnetic Resonance Imaging 01/2009; 27(1):108-19. · 1.99 Impact Factor
