Stromal cells from term fetal membrane are highly suppressive in allogeneic settings in vitro.

Bone marrow-derived mesenchymal stromal cells (BM-MSCs) have immunosuppressive properties and have been used to treat steroid-refractory acute graft-versus-host disease (GVHD) in stem cell transplant patients. Cells with similar capacities can also be found in term placental tissue. We have isolated stromal cells from term fetal membrane (FMSCs), umbilical cords (UCSCs) and placental villi (PVSCs) as well as from bone marrow and compared their immunoregulatory capacity in allogeneic settings. We found that FMSCs and UCSCs suppressed proliferation significantly in mixed lymphocyte reactions (MLRs), whereas PVSCs showed inconsistent suppressive effects. When added to MLR cultures, FMSCs suppressed the production of interferon (IFN)-γ and interleukin (IL)-17, whereas UCSCs and PVSCs promoted the production of IL-17 instead. Secretion of IL-10 was increased after addition of FMSCs and UCSCs. In this setting, BM-MSCs had no significant effect on secretion of IFN-γ, IL-17 or IL-10 in MLR cultures. When analysing the expression of adhesion markers, we noted that FMSCs expressed the highest levels of CD29 (ß1), CD49d (α4) and CD54 (ICAM-1) compared to the other types of stromal cells. Thus, our data indicate that stromal cells isolated from term fetal membrane have great immunosuppressive capacity in terms of proliferation and production of proinflammatory cytokines from alloreactive T cells, and also promote anti-inflammatory IL-10. They express high levels of integrins that may be of importance in homing to inflamed tissues. Fetal membrane may provide a valuable source of cells with immunosuppressive properties and could possibly be used for treatment of acute GVHD and other inflammatory disorders.

Dark lumen MR colonography: can high spatial resolution VIBE imaging improve the detection of colorectal masses?

PURPOSE: To assess whether the detection of colorectal lesions can be improved using high spatial resolution VIBE imaging. MATERIALS AND METHODS: 48 patients underwent same-day dark lumen MR colonography (MRC) and conventional colonoscopy (CC) as the standard for the detection of colorectal masses. MRC was performed using contrast-enhanced standard and high spatial resolution T1-weighted 3D VIBE sequences. The findings and the image quality of the standard and high spatial resolution VIBE sequences were compared qualitatively and quantitatively. The findings of both sequences regarding colorectal lesions were compared to those of a subsequently performed colonoscopy. RESULTS: The high spatial resolution VIBE sequence significantly improved the quantitative image quality (CNR 54.0 vs. 36.8). However, high spatial resolution VIBE imaging did not detect more colorectal lesions than the standard VIBE sequence. In addition, none of the sequences employed was able to detect lesions with a diameter of less than 5 mm (CC 40 lesions). However, 13 colorectal lesions with a diameter of greater than 5 mm were detected by both sequences (CC 15). CONCLUSION: High spatial resolution VIBE imaging did not improve the detection of colorectal masses and MRC fails to detect colorectal lesions with a diameter of less than 5 mm.

[State of the art of MR colonoscopy]. / Aktuelle Standards der MR-Kolonographie.

MR colonoscopy is suitable for colorectal cancer screening. This imaging modality is non-invasive, has no harmful side effects and provides a high diagnostic accuracy. MR colonoscopy has been found to be highly sensitive and specific in detecting colorectal lesions > 10 mm in size. Since colonic polyps are difficult to differentiate from residual stool, colonic cleansing has been unavoidable but reduces patient acceptance. Cleansing of the bowel can be avoided if the signal of stool is rendered different from its surrounding. This can be achieved by adding an agent to the food that tags the feces (fecal tagging). This article describes current techniques of MR colonoscopy as well as first results with fecal tagging.

Large nontransplanted hepatocellular carcinoma in woodchucks: treatment with adenovirus-mediated delivery of interleukin 12/B7.1 genes.

BACKGROUND: Cytokine-based gene therapy strategies efficiently stimulate immune responses against many established transplanted tumors, leading to rejection of the tumor. In this study, we investigated the therapeutic potential of cancer immunotherapy in a clinically more relevant model, woodchucks with primary hepatocellular carcinomas induced by woodchuck hepatitis virus. METHODS: Large (2-5 cm), established intrahepatic tumors were given an injection once with 1 x 10(9) plaque-forming units of AdIL-12/B7.1, an adenovirus vector carrying genes for murine interleukin 12 and B7.1, or of AdEGFP, the control virus, and regression of the tumors was then monitored. Five animals were used in total. RESULTS: In four tumor-bearing animals, the antitumor response was assessed by autopsy and histologic analysis within 1-2 weeks after treatment. In all animals treated with AdIL-12/B7.1 therapy versus AdEGFP therapy, we observed substantial tumor regression (P =.006; two-sided unpaired Student's t test) accompanied by a massive infiltration of T lymphocytes. These tumors also contained increased levels of CD4(+) and CD8(+) T cells and interferon gamma (IFN gamma). In continuously growing tumor nodules given an injection of the control virus or in nontumoral liver, no such effects (i.e., tumor regression and increased levels of CD4(+) and CD8(+) T cells and IFN gamma) were detected. In the fifth animal, monitored for long-term antitumor efficacy by magnetic resonance imaging (MRI) after intratumoral vector administration by MRI guidance, the tumor was almost completely eliminated (> or = 95%) 7 weeks after treatment. CONCLUSION: Adenovirus vector-based immunotherapy appears to be an effective treatment of large nontransplanted (orthotopic) tumors that acquire malignant characteristics in a stepwise process, reflecting the real-world scenario of hepatocellular carcinoma in humans.

Equilibrium-phase MR angiography of the aortoiliac and renal arteries using a blood pool contrast agent.

OBJECTIVE: The purpose of this study was to determine the diagnostic usefulness of a new blood pool contrast agent, NC100150, for assessing the aortoiliac and renal arteries. SUBJECTS AND METHODS: Twenty patients with hemodynamically significant stenosis (> or =50% of luminal diameter) of the iliac or renal arteries or an aortic aneurysm documented by digital subtraction angiography underwent MR angiography at 1.5 T after administration of NC100150. Three-dimensional MR angiographic data sets were collected ill the equilibrium phase. In a prospective analysis, each vascular segment (16 segments per arterial tree) was evaluated. RESULTS: All patients tolerated the NC100150 administration well. Mean contrast-to-noise ratios of the vascular data collected in the equilibrium phase of NC100150 was 3.3+/-15.9. Compared with digital subtraction angiography, the sensitivity and specificity of MR angiography for the renal arteries were 82% and 98%, respectively; for the common iliac arteries, 86% and 97%, respectively; for the external iliac arteries, 80% and 100%, respectively; and for the internal iliac arteries, 71% and 977, respectively. All 83 aneurysmal changes revealed by digital subtraction angiograpy of the aortoiliac arteries were well displayed on the MR angiographic data sets. CONCLUSION: Equilibrium-phase NC 00150-enhanced three-dimensional MR angiography shows high specificity when evaluating the abdominal and pelvic vascular systems, but the attendant venous overlap can limit the assessment of stenosis in renal and pelvic arterial segments.

Magnetic resonance-based assessment of global coronary flow and flow reserve and its relation to left ventricular functional parameters: a comparison with positron emission tomography.

BACKGROUND: Measurement of coronary sinus blood flow (CSF) by phase-contrast magnetic resonance (PC-MR) imaging at rest and during hyperemia may allow noninvasive assessment of global coronary hemodynamics. METHODS AND RESULTS: Sixteen healthy volunteers (age, 22 to 32 years) were examined with MR and PET in random order within 1 to 2 days. At rest and during hyperemia (dipyridamole 0.56 mg/kg), CSF was measured by a cine PC-MR technique (temporal resolution, 40 ms; spatial resolution, 1.25x0.8 mm(2)), and myocardial blood flow (MBF) was measured by [(13)N]NH(3) PET. PET and MR agreed closely for coronary flow reserve (CFR; mean difference, 2.2+/-14.7%; Bland-Altman method). CSF divided by either total left ventricular mass or an estimate of drained myocardium (LVM(drain)) correlated highly with PET flow data (r=0.93 and 0.95, respectively) and with measures of oxygen demand, ie, heart rate, afterload-corrected fiber shortening, and peak systolic stress determined by MR (overall correlation coefficients, 0.81 and 0.87, respectively, multivariate analysis). CSF/LVM(drain) did not differ significantly from PET-derived MBF (difference, 3.6+/-16.6%). In orthotopic heart transplant recipients (n=9), CFR was reduced and blood supply-demand relationships at rest were shifted toward higher flows (P<0.0001). CONCLUSIONS: This integrated MR approach allows comprehensive assessment of autoregulated and hyperemic coronary flow and is suitable for serial measurements in patients. In transplanted hearts, elevated resting flow is the major cause of reduced CFR.

[Contrast-enhanced 3D MR-angiography of the thorax, abdomen and lower extremities]. / Kontrastverstärkte 3D-MR-Angiographie in Thorax, Abdomen und Peripherie.

Contrast-enhanced 3D MR angiography permits comprehensive assessment of the arterial system in the chest, abdomen und lower extremities. The method combines intravenous bolus application of a non-nephrotoxic, paramagnetic, extracellular contrast agent with the acquisition of a fast 3D data set. High contrast between the vascular lumen and surrounding tissues, inherent three-dimensionality and the ability to collect image data in the chest and abdomen under apnea conditions all contribute to excellent image quality. Contrast-enhanced 3D MRA is being employed in many centers throughout the world for the evaluation of various arterial pathologies. This review provides a technical overview and critically discusses the clinical applications in the chest, abdomen and lower extremities based upon the available literature and several clinical examples.