33 research outputs found
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
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
Meta-Analysis of Cell-based CaRdiac stUdiEs (ACCRUE) in patients with acute myocardial infarction based on individual patient data
RATIONALE: The meta-Analysis of Cell-based CaRdiac study is the first prospectively declared collaborative multinational database, including individual data of patients with ischemic heart disease treated with cell therapy.
OBJECTIVE: We analyzed the safety and efficacy of intracoronary cell therapy after acute myocardial infarction (AMI), including individual patient data from 12 randomized trials (ASTAMI, Aalst, BOOST, BONAMI, CADUCEUS, FINCELL, REGENT, REPAIR-AMI, SCAMI, SWISS-AMI, TIME, LATE-TIME; n=1252).
METHODS AND RESULTS: The primary end point was freedom from combined major adverse cardiac and cerebrovascular events (including all-cause death, AMI recurrance, stroke, and target vessel revascularization). The secondary end point was freedom from hard clinical end points (death, AMI recurrence, or stroke), assessed with random-effects meta-analyses and Cox regressions for interactions. Secondary efficacy end points included changes in end-diastolic volume, end-systolic volume, and ejection fraction, analyzed with random-effects meta-analyses and ANCOVA. We reported weighted mean differences between cell therapy and control groups. No effect of cell therapy on major adverse cardiac and cerebrovascular events (14.0% versus 16.3%; hazard ratio, 0.86; 95% confidence interval, 0.63-1.18) or death (1.4% versus 2.1%) or death/AMI recurrence/stroke (2.9% versus 4.7%) was identified in comparison with controls. No changes in ejection fraction (mean difference: 0.96%; 95% confidence interval, -0.2 to 2.1), end-diastolic volume, or systolic volume were observed compared with controls. These results were not influenced by anterior AMI location, reduced baseline ejection fraction, or the use of MRI for assessing left ventricular parameters.
CONCLUSIONS: This meta-analysis of individual patient data from randomized trials in patients with recent AMI revealed that intracoronary cell therapy provided no benefit, in terms of clinical events or changes in left ventricular function.
CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01098591