Results of a phase 1, randomized, double-blind, placebo-controlled trial of bone marrow mononuclear stem cell administration in patients following ST-elevation myocardial infarction. Intracoronary infusion of mononuclear cells from bone marrow or peripheral blood compared with standard therapy in patients after acute myocardial infarction treated by primary percutaneous coronary intervention: results of the randomized controlled HEBE trial. Autologous transplantation of granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells improves critical limb ischemia in diabetes. Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. Repeated autologous bone marrow mononuclear cell therapy in patients with large myocardial infarction. Intracoronary autologous mononucleated bone marrow cell infusion for acute myocardial infarction: results of the randomized multicenter BONAMI trial. Endometrial local injury improves the pregnancy rate among recurrent implantation failure patients undergoing in vitro fertilisation/intra cytoplasmic sperm injection: a randomised clinical trial. Systolic function of patients with myocardial infarction undergoing autologous bone marrow transplantation. Effects of intracoronary injection of mononuclear bone marrow cells on left ventricular function, arrhythmia risk profile, and restenosis after thrombolytic therapy of acute myocardial infarction.
Initial clinical trials from Europe have demonstrated that the administration of bone marrow-derived mononuclear cells (BMCs) may improve left ventricular (LV) function in patients following ST-elevation myocardial infarction (STEMI). However, results from trials performed in the United States have not yet been presented.
                We developed a phase 1, randomized, placebo-controlled, double-blind trial to investigate the effects of BMC administration in patients following STEMI on recovery of LV function using cardiac magnetic resonance imaging (cMRI). Forty patients with moderate to large anterior STEMIs were randomized to 100 million intracoronary BMCs versus placebo 3 to 10 days following successful primary angioplasty and stenting (percutaneous coronary intervention) of the left anterior descending coronary artery.
                Administration of BMC was safely performed in a high-risk cohort with minimal major adverse clinical event rates, and all patients remain alive to date. Left ventricular ejection fraction increased from 49.0% +/- 9.5% at baseline to 55.2% +/- 9.8% at 6 months by cMRI in the BMC group (P < .05), which was not different from the increase in the placebo group (48.6% +/- 8.5% to 57.0% +/- 13.4%, P < .05). Left ventricular end-diastolic volume decreased by 4 mL/m(2) in the BMC group at 6 months but increased significantly in the placebo group (17 mL/m(2), P < .01).
                This phase 1 study from the United States confirms the ongoing safety profile of BMC administration in patients following STEMI. The improvement in LV ejection fraction at 6 months by cMRI in the cell therapy group was not different than the placebo group. However, BMC administration had a favorable effect on LV remodeling at 6 months.
                2010 Mosby, Inc. All rights reserved. Previous trials that investigated cell therapy as an adjunctive therapy after acute myocardial infarction (AMI) have shown conflicting results. We designed a randomized controlled trial to determine the effect of intracoronary infusion of mononuclear cells from bone marrow (BM) or peripheral blood in patients with AMI.
                In a multicentre trial, 200 patients with large first AMI treated with primary percutaneous coronary intervention were randomly assigned to either intracoronary infusion of mononuclear BM cells (n = 69), mononuclear peripheral blood cells (n = 66), or standard therapy (without placebo infusion) (n = 65). Mononuclear cells were delivered intracoronary between 3 and 8 days after AMI. Regional and global left ventricular myocardial function and volumes were assessed by magnetic resonance imaging before randomization and at 4 months, and clinical events were reported. The primary endpoint of the percentage of dysfunctional left ventricular segments that improved during follow-up did not differ significantly between either of the treatment groups and control: 38.6 ± 24.7% in the BM group, 36.8 ± 20.9% in the peripheral blood group, and 42.4 ± 18.7% in the control group (P = 0.33 and P = 0.14). Improvement of left ventricular ejection fraction was 3.8 ± 7.4% in the BM group, 4.2 ± 6.2% in the peripheral blood group when compared with 4.0 ± 5.8% in the control group (P = 0.94 and P = 0.90). Furthermore, the three groups did not differ significantly in changes in left ventricular volumes, mass, and infarct size and had similar rates of clinical events.
                Intracoronary infusion of mononuclear cells from BM or peripheral blood following AMI does not improve regional or global systolic myocardial function in the HEBE trial.
                The Netherlands Trial Register #NTR166 (www.trialregister.nl) and the International Standard Randomised Controlled Trial, #ISRCTN95796863 (http://isrctn.org). To assess the application of autologous transplantation of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood mononuclear cells (PBMNCs) in the treatment of critical limb ischemia (CLI) of diabetic patients and to evaluate the safety, efficacy, and feasibility of this novel therapeutic approach.
                Twenty-eight diabetic patients with CLI were enrolled and randomized to either the transplant group or the control group. In the transplant group, the patients received subcutaneous injections of recombinant human G-CSF (600 microg/day) for 5 days to mobilize stem/progenitor cells, and their PBMNCs were collected and transplanted by multiple intramuscular injections into ischemic limbs. All of the patients were followed up after at least 3 months.
                At the end of the 3-month follow-up, the main manifestations, including lower limb pain and ulcers, were significantly improved in the patients of the transplant group. Their laser Doppler blood perfusion of lower limbs increased from 0.44 +/- 0.11 to 0.57 +/- 0.14 perfusion units (P < 0.001). Mean ankle-brachial pressure index increased from 0.50 +/- 0.21 to 0.63 +/- 0.25 (P < 0.001). A total of 14 of 18 limb ulcers (77.8%) of transplanted patients were completely healed after cell transplantation, whereas only 38.9% of limb ulcers (7 of 18) were healed in the control patients (P = 0.016 vs. the transplant group). No adverse effects specifically due to cell transplantation were observed, and no lower limb amputation occurred in the transplanted patients. In contrast, five control patients had to receive a lower limb amputation (P = 0.007, transplant vs. control group). Angiographic scores were significantly improved in the transplant group when compared with the control group (P = 0.003).
                These results provide pilot evidence indicating that the autologous transplantation of G-CSF-mobilized PBMNCs represents a simple, safe, effective, and novel therapeutic approach for diabetic CLI. Previous studies have shown improvement in left ventricular function after intracoronary injection of autologous cells derived from bone marrow (BMC) in the acute phase of myocardial infarction. We designed a randomized, controlled trial to further investigate the effects of this treatment.
                Patients with acute ST-elevation myocardial infarction of the anterior wall treated with percutaneous coronary intervention were randomly assigned to the group that underwent intracoronary injection of autologous mononuclear BMC or to the control group, in which neither aspiration nor sham injection was performed. Left ventricular function was assessed with the use of electrocardiogram-gated single-photon-emission computed tomography (SPECT) and echocardiography at baseline and magnetic resonance imaging (MRI) 2 to 3 weeks after the infarction. These procedures were repeated 6 months after the infarction. End points were changes in the left ventricular ejection fraction (LVEF), end-diastolic volume, and infarct size.
                Of the 50 patients assigned to treatment with mononuclear BMC, 47 underwent intracoronary injection of the cells at a median of 6 days after myocardial infarction. There were 50 patients in the control group. The mean (+/-SD) change in LVEF, measured with the use of SPECT, between baseline and 6 months after infarction for all patients was 7.6+/-10.4 percentage points. The effect of BMC treatment on the change in LVEF was an increase of 0.6 percentage point (95% confidence interval [CI], -3.4 to 4.6; P=0.77) on SPECT, an increase of 0.6 percentage point (95% CI, -2.6 to 3.8; P=0.70) on echocardiography, and a decrease of 3.0 percentage points (95% CI, 0.1 to -6.1; P=0.054) on MRI. The two groups did not differ significantly in changes in left ventricular end-diastolic volume or infarct size and had similar rates of adverse events.
                With the methods used, we found no effects of intracoronary injection of autologous mononuclear BMC on global left ventricular function.
                2006 Massachusetts Medical Society We sought to determine whether repeat administration of bone marrow mononuclear cells (BMC) can improve left ventricular function compared with a single infusion in patients with large acute myocardial infarction (AMI).
                Thirty-nine patients with a ST-elevation AMI of the anterior wall and a significantly decreased left ventricular ejection fraction (LVEF 20-39%) were randomly assigned to three groups following primary percutaneous coronary intervention: Group A (n = 12) received a single intracoronary infusion of BMC (1.9 +/- 1.2 x 10(8)) at 3-7 days after AMI; Group B (n = 15) received BMC administration both at 3-7 days (2.0 +/- 1.4 x 10(8)) and at 3 months (2.1 +/- 1.7 x 10(8)); and the control group (CON, n = 12) received one placebo injection at 3-7 days. We noted no severe complications associated with the BMC transfer. The increase in LVEF evaluated by magnetic resonance imaging (MRI) after 12 months in Group B (11.7 +/- 2.6%) was significantly greater than that in Group A (7.2 +/- 1.6%, P < 0.001) or in CON (2.9 +/- 2.0%, P < 0.001). Magnetic resonance imaging-derived myocardial infarct size decreased significantly in Group B compared with Group A (11.3 +/- 2.7% vs. 6.3 +/- 1.6%, P < 0.001).
                Data from this preliminary study suggest that repeated BMC administration might be a safe and feasible therapeutic strategy for patients with large AMI. Intracoronary administration of autologous bone marrow cells (BMCs) leads to a modest improvement in cardiac function, but the effect on myocardial viability is unknown. The aim of this randomized multicentre study was to evaluate the effect of BMC therapy on myocardial viability in patients with decreased left ventricular ejection fraction (LVEF) after acute myocardial infarction (AMI) and to identify predictive factors for improvement of myocardial viability.
                One hundred and one patients with AMI and successful reperfusion, LVEF ≤45%, and decreased myocardial viability (resting Tl201-SPECT) were randomized to either a control group (n = 49) or a BMC group (n = 52). Primary endpoint was improvement of myocardial viability 3 months after AMI. Baseline mean LVEF measured by radionuclide angiography was 36.3 ± 6.9%. Bone marrow cell infusion was performed 9.3 ± 1.7 days after AMI. Myocardial viability improved in 16/47 (34%) patients in the BMC group compared with 7/43 (16%) in the control group (P = 0.06). The number of non-viable segments becoming viable was 0.8 ± 1.1 in the control group and 1.2 ± 1.5 in the BMC group (P = 0.13). Multivariate analysis including major post-AMI prognostic factors showed a significant improvement of myocardial viability in BMC vs. control group (P = 0.03). Moreover, a significant adverse role for active smoking (P = 0.04) and a positive trend for microvascular obstruction (P = 0.07) were observed.
                Intracoronary autologous BMC administration to patients with decreased LVEF after AMI was associated with improvement of myocardial viability in multivariate-but not in univariate-analysis. A large multicentre international trial is warranted to further document the efficacy of cardiac cell therapy and better define a group of patients that will benefit from this therapy. Clinical Trial Registration Information: URL: http://www.clinicaltrials.gov. Unique identifier NCT00200707. Implantation failure is the most important cause of recurrent in vitro fertilisation (IVF)/intra cytoplasmic sperm injection (ICSI) failure. It has been reported that endometrial injury using a biopsy catheter resulted in a higher pregnancy rate in following cycle of treatment. The local endometrial trauma increases the implantation rate through the release of chemical mediators such as histamine and growth factor.
                To evaluate the influence of endometrial biopsy on increasing implantation rate in patients with recurrent implantation failures.
                In a randomised control trial study, 115 women each with at least two implantation failures were randomly assigned to two groups. In the case group, endometrial biopsy was obtained from patients in the luteal phase of previous cycle, and implantation and clinical pregnancy rates were compared with those of patients in the control group.
                The implantation rate was determined as 10.9% in the biopsy group compared to 3.38% in the controls. The clinical pregnancy rate was significantly higher in the case group than in controls (27.1% and 8.9% respectively).
                The results suggest that pregnancy outcome increases through IVF or ICSI after endometrial biopsy. Several studies have been published on the effect of bone-marrow stem cells on the left ventricle when acting on post- acute myocardial infarction remodeling. However, the results have been controversial.
                To carry out an echocardiographic analysis of the systolic function of patients with acute myocardial infarction after autologous mononuclear bone marrow cell transplantation (AMBMCT) as performed via the intracoronary and intravenous routes.
                This is an open-label, prospective, randomized study. Inclusion criteria: patients admitted for ST-elevation acute myocardial infarction (MI) who had undergone mechanical or chemical reperfusion within 24 hours of the onset of symptoms and whose echocardiogram showed decreased segmental wall motion and fixed perfusion defect related to the culprit artery. Autologous bone marrow was aspirated from the posterior iliac crest under sedation and analgesia of the patients randomly assigned for the treatment group. After laboratory manipulation, intracoronary or intravenous injection of 100 x 106 mononuclear cells was performed. Echocardiography (Vivid 7) was used to assess ventricular function before and three and six months after cell infusion.
                A total of 30 patients were included, 14 in the arterial group (AG), 10 in the venous group (VG), and six in the control group (CG). No statistical difference was found between the groups for the echocardiographic parameters studied.
                Autologous mononuclear bone marrow cell transplantation did not improve the echocardiographic parameters of systolic function. To assess the efficacy and safety of bone marrow cell (BMC) therapy after thrombolytic therapy of an acute ST-elevation myocardial infarction (STEMI).
                Patients with STEMI treated with thrombolysis followed by percutaneous coronary intervention (PCI) 2-6 days after STEMI were randomly assigned to receive intracoronary BMCs (n = 40) or placebo medium (n = 40), collected and prepared 3-6 h prior PCI and injected into the infarct artery immediately after stenting. Efficacy was assessed by the measurement of global left ventricular ejection fraction (LVEF) by left ventricular angiography and 2-D echocardiography, and safety by measuring arrhythmia risk variables and restenosis of the stented vessel by intravascular ultrasound. At 6 months, BMC group had a greater absolute increase of global LVEF than placebo group, measured either by angiography (mean +/- SD increase 7.1 +/- 12.3 vs. 1.2 +/- 11.5%, P = 0.05) or by 2-D echocardiography (mean +/- SD increase 4.0 +/- 11.2 vs. -1.4 +/- 10.2%, P = 0.03). No differences were observed between the groups in the adverse clinical events, arrhythmia risk variables, or the minimal lumen diameter of the stented coronary lesion.
                Intracoronary BMC therapy is associated with an improvement of global LVEF and neutral effects on arrhythmia risk profile and restenosis of the stented coronary lesions in patients after thrombolytic therapy of STEMI.
The data from the published trials suggest that there is insufficient evidence to support this treatment. These results were based on only two trials which had a very small number of participants. Therefore evidence from larger randomised controlled trials is needed in order to provide adequate statistical power to assess the role of intramuscular mononuclear cell implantation in patients with CLI.