Directing cell therapy to anatomic target sites in vivo with magnetic resonance targeting

Cell-based therapy exploits modified human cells to treat diseases but its targeted application in specific tissues, particularly those lying deep in the body where direct injection is not possible, has been problematic. Here we use a magnetic resonance imaging (MRI) system to direct macrophages carrying an oncolytic virus, Seprehvir, into primary and metastatic tumour sites in mice. To achieve this, we magnetically label macrophages with super-paramagnetic iron oxide nanoparticles and apply pulsed magnetic field gradients in the direction of the tumour sites. Magnetic resonance targeting guides macrophages from the bloodstream into tumours, resulting in increased tumour macrophage infiltration and reduction in tumour burden and metastasis. Our study indicates that clinical MRI scanners can not only track the location of magnetically labelled cells but also have the potential to steer them into one or more target tissues

New ß-decaying state in 214Bi

A new β-decaying state in 214Bi has been identified at the ISOLDE Decay Station at the CERN-ISOLDE facility. A preferred Iπ = (8−) assignment was suggested for this state based on the β-decay feeding pattern to levels in 214Po and shell-model calculations. The half-life of the Iπ = (8−) state was deduced to be T1/2 = 9.39(10) min. The deexcitation of the levels populated in 214Po by the β decay of this state was investigated via γ -γ coincidences and a number of new levels and transitions was identified. Shell-model calculations for excited states in 214Bi and 214Po were performed using two different effective interactions: the H208 and the modified Kuo-Herling particle interaction. Both calculations agree on the interpretation of the new β-decaying state as an Iπ = 8− isomer and allow for tentative assignment of shell-model states to several high-spin states in 214Po.peerReviewe

New ß-decaying state in 214Bi

A new β-decaying state in 214Bi has been identified at the ISOLDE Decay Station at the CERN-ISOLDE facility. A preferred Iπ = (8−) assignment was suggested for this state based on the β-decay feeding pattern to levels in 214Po and shell-model calculations. The half-life of the Iπ = (8−) state was deduced to be T1/2 = 9.39(10) min. The deexcitation of the levels populated in 214Po by the β decay of this state was investigated via γ -γ coincidences and a number of new levels and transitions was identified. Shell-model calculations for excited states in 214Bi and 214Po were performed using two different effective interactions: the H208 and the modified Kuo-Herling particle interaction. Both calculations agree on the interpretation of the new β-decaying state as an Iπ = 8− isomer and allow for tentative assignment of shell-model states to several high-spin states in 214Po.peerReviewe

Discrepancy between short-term and long-term effects of bone marrow-derived cell therapy in acute myocardial infarction: a systematic review and meta-analysis

Abstract Background Bone marrow-derived cell therapy has been used to treat acute myocardial infarction. However, the therapeutic efficacy of this approach remains controversial. Here, we performed a systematic review and meta-analysis to evaluate short-term and long-term effectiveness of bone marrow-derived therapy. Methods We searched eight databases (Ovid-Medline, Ovid-EMBASE, Cochrane Library, KoreaMed, KMBASE, KISS, RISS, and KisTi) up to December 2014. Demographic characteristics, clinical outcomes, and adverse events were analyzed. We identified 5534 potentially relevant studies; 405 were subjected to a full-text review. Forty-three studies with 2635 patients were included in this review. Results No safety issues related to cell injection were reported during follow-up. At 6 months, cell-injected patients showed modest improvements in left ventricular ejection fraction (LVEF) compared with the control group. However, there were no differences between groups at other time points. In the cardiac MRI analysis, there were no significant differences in infarct size reduction between groups. Interestingly, mortality tended to be reduced at the 3-year follow-up, and at the 5-year follow-up, cell injection significantly decreased all-cause mortality. Conclusions This meta-analysis demonstrated discrepancies between short-term LV functional improvement and long-term all-cause mortality. Future clinical trials should include long-term follow-up outcomes to validate the therapeutic efficacy of cell therapy

Microvascular obstruction identifies a subgroup of patients who benefit from stem cell therapy following ST-elevation myocardial infarction

International audienceBackground: Microvascular obstruction (MVO) is associated with greater infarct size, adverse left-ventricular (LV) remodeling and reduced ejection fraction following ST-elevation myocardial infarction (STEMI). We hypothesized that patients with MVO may constitute a subgroup of patients that would benefit from intracoronary stem cell delivery with bone marrow mononuclear cells (BMCs) given previous findings that BMCs tended to improve LV function only in patients with significant LV dysfunction.Methods and results: We analyzed the cardiac MRIs of 356 patients (303 M, 53 F) with anterior STEMIs who received autologous BMCs or placebo / control as part of 4 randomized clinical trials that included the Cardiovascular Cell Therapy Research Network (CCTRN) TIME trial and its pilot, the multicenter French BONAMI trial and SWISS-AMI trials. A total of 327 patients had paired imaging data at 1 year. All patients received 100 to 150 million intracoronary autologous BMCs or placebo / control 3 to 7 days following primary PCI and stenting. LV function, volumes, infarct size and MVO were assessed prior to infusion of BMCs and 1 year later. Patients with MVO (n = 210) had reduced LVEF and much greater infarct size and LV volumes compared to patients without MVO (n = 146) (P < .01). At 12 months, patients with MVO who received BMCs had significantly greater recovery of LVEF compared to those patients with MVO who received placebo (absolute difference = 2.7%; P < .05). Similarly, left-ventricular end-diastolic (LVEDVI) and end-systolic volume indices (LVESVI) demonstrated significantly less adverse remodeling in patients with MVO who received BMCs compared to placebo. In contrast, no improvement in LVEF or LV volumes was observed in those patients without MVO who received BMCs compared to placebo.Conclusions: The presence of MVO on cardiac MRI following STEMI identifies a subgroup of patients who benefit from intracoronary stem cell therapy