To compare the anti-inflammatory and endothelial progenitor cell mobilizing effects of ramipril and telmisartan in patients presenting with acute coronary syndrome (ACS), 42 patients with ACS were randomized after successful percutaneous coronary intervention to ramipril 5 mg/day (22 patients) or telmisartan 80 mg/day (20 patients). Peripheral blood samples were drawn at baseline and at 20 days to measure high-sensitivity C-reactive protein and to assess 4 populations of progenitor cells by flow cytometry, namely CD34+/KDR+, CD34+/CD133+, CD34+/CD133+/CD45-, and CD34+/KDR+/CD45- cells. High-sensitivity C-reactive protein levels, similar in the 2 groups at baseline, were significantly more decreased by telmisartan than by ramipril at follow up (p = 0.013 for time-by-drug interaction). The main effect for time was also significant (p <0.001). CD34+/KDR+ and CD34+/CD133+ cells were similar at baseline and did not change over time (p = 0.2 and p = 0.1, respectively). In contrast, for CD34+/KDR+/CD45- and CD34+/CD133+/CD45- cells, a significant increase with time was seen (p = 0.02 and p = 0.002, respectively) and no differential effect of either drug was seen. In conclusion, telmisartan shows a more potent anti-inflammatory effect than ramipril after an ACS. The 2 drugs do not show a differential effect on endothelial progenitor cell mobilization.

The aim of this study was to test safety and feasibility of myoblast transplantation with the Biosense-NOGA (Diamond Bar, California) 3-dimensional-guided endomyocardial delivery system.

Peripheral blood stem cells (PBSC) are one of the most promising stem cell sources for treatment of ischaemic heart disease. However, the experience of mobilisation and collection of PBSC using granulocyte-colony stimulating factor (G-CSF) in patients with myocardial infarction (MI) is still limited. We report our experiences with the feasibility and safety of collection of mobilised PBSC with G-CSF in MI patients, and the influence of acute ischaemia on efficacy of PBSC collection.

Granulocyte-colony stimulating factor (G-CSF) is used to mobilize CD34+ haematopoietic stem cells from the bone marrow to the peripheral blood. We proposed to use cell subsets induced by G-CSF to slow down disease progression in patients with amyotrophic lateral sclerosis (ALS). Patients with definite or probable ALS were assigned in a double-blind manner to receive G-CSF or placebo every three months for a year. The primary outcome measure was the functional decline, measured by the revised ALS Functional Rating Scale, Revised (ALSFRS-R) score. Secondary outcome measures included vital capacity, manual muscle strength, compound muscle action potential amplitudes, neurophysiological index, and McGill single item quality of life score (QoL). Thirty-nine patients were enrolled. Seventeen patients who received G-CSF and 18 who received placebo were evaluated. G-CSF was effective in mobilizing CD34+ to blood. The outcome measures used showed no statistically significant benefit, although there was a trend of slowing disease progression following two G-CSF treatments, as shown by lower slopes of ALSFRS-R and QoL in the first six treatment months. The treatment had no major side-effects. G-CSF administration in ALS patients caused successful mobilization of autologous bone marrow cells, but was not effective in slowing down disease deterioration.

To validate a novel system for embryonic DNA fingerprinting which can reliably distinguish sibling embryos from each other.

Endothelial progenitor cells (EPCs) play an important role in the maintenance of vascular integrity. Lipid lowering therapy (LLT) with statins may contribute to biologically relevant activities including the proliferation of endothelial cells. The physiological role of microRNA (miR)-221/222, a newly discovered class of small RNA, is closely linked to the proliferation of endothelial cells. We therefore investigated whether LLT with statins might affect miR-221/222 expression in EPCs obtained from patients with coronary artery disease (CAD).

This phase 3, multicenter, randomized (1:1), double-blind, placebo-controlled study evaluated the safety and efficacy of plerixafor with granulocyte colony-stimulating factor (G-CSF) in mobilizing hematopoietic stem cells in patients with multiple myeloma. Patients received G-CSF (10 microg/kg) subcutaneously daily for up to 8 days. Beginning on day 4 and continuing daily for up to 4 days, patients received either plerixafor (240 microg/kg) or placebo subcutaneously. Starting on day 5, patients began daily apheresis for up to 4 days or until more than or equal to 6 x 10(6) CD34(+) cells/kg were collected. The primary endpoint was the percentage of patients who collected more than or equal to 6 x 10(6) CD34(+) cells/kg in less than or equal to 2 aphereses. A total of 106 of 148 (71.6%) patients in the plerixafor group and 53 of 154 (34.4%) patients in the placebo group met the primary endpoint (P < .001). A total of 54% of plerixafor-treated patients reached target after one apheresis, whereas 56% of the placebo-treated patients required 4 aphereses to reach target. The most common adverse events related to plerixafor were gastrointestinal disorders and injection site reactions. Plerixafor and G-CSF were well tolerated, and significantly more patients collected the optimal CD34(+) cell/kg target for transplantation earlier compared with G-CSF alone. This study is registered at www.clinicaltrials.gov as #NCT00103662.

Procedures to prevent severe graft-versus-host disease (GVHD) delay immune reconstitution secondary to transplants of haploidentical haemopoietic stem cells for the treatment of leukaemia, leading to high rates of late infectious mortality. We aimed to systematically add back genetically engineered donor lymphocytes to facilitate immune reconstitution and prevent late mortality.

Filgrastim XM02 is a biosimilar non-glycosylated recombinant methionyl form of human granulocyte colony-stimulating factor (r-MetHuG-CSF) expressed in Escherichia coli for subcutaneous and intravenous administration in the treatment of different forms of neutropenia and stem cell mobilization. This study was conducted to compare the pharmacokinetic and pharmacodynamic characteristics of the new biosimilar filgrastim XM02 with the marketed filgrastim (Neupogen).

Celiac disease (CD) is a chronic inflammatory enteropathy of the small bowel resulting from a local TH1-mediated reaction to wheat gliadins and barley, rye and oat prolamins with the development of auto-antibodies to transglutaminases. As well as for other chronic inflammatory diseases, genetic background and environmental factors participate to pathogenesis. An increased traffic of CD34+ hemopoietic precursor and stem cells (HPC) has been reported in peripheral blood (PB) of subjects with allergic diseases that share in their pathogenesis immuno-mediated reactions, genetic and environmental factors. The aim of the present work was to investigate the CD34+ cell traffic and H2/H1 polarization of lymphoid T-cell lineage, in the peripheral blood of subjects with CD, by means of flow-cytometric techniques. Group A of control was of 20 healthy subjects, aged 5 to 58 years. Study population (Group B) was of twenty-eight patients, all females aged 13 to 70, receiving firstly a CD diagnosis at the SS Annunziata Hospital Digestive Physiopathology Out-standings' by means of clinical, serologic and small intestinal biopsy findings. Peripheral CD34+ HPCs were significantly increased in Group B (median value 0.16) when compared with Group A (median value 0.03) (p 0.0001) but did not correlate either with anti-transglutaminase (tTG) antibody levels (IgA: p 0.226; IgG: p 0.810) or with histological damage severity (p 0.41) that, on the contrary, was significantly related with anti-tTG IgA antibodies (p 0.027). Celiac circulating CD3+CD4+ lymphocytes expressed a chemokine-receptor pattern Th2-skewed in all but three patients investigated. Concluding, the CD34+ HPC highly increased peripheral traffic observed in celiac disease appears more related to a basic and emerging as common defect shared by chronic inflammatory diseases than to the gliadin-specific Th1 local reactions. Data are consistent with a potential NFkappaB deficiency and consequent prevalence of apoptotic versus survival programs leading to excessive cell-death; to replace lost cells a supplementary bone-marrow derived precursors supply, further to that physiologically provided by the gut stem cell "niches" that are cryptopatches, could be required.

To observe the effect of Yiqi Wenyang Huoxue Recipe (YWHR) on bone marrow stem cells' mobilization and heart function of myocardial infarction (MI) patients.

The aim of this study was to evaluate the apoptotic damage to bone marrow cells caused by three chemotherapy regimens for advanced Hodgkin's lymphoma, ABVD, COPPEBVCAD and BEACOPP, which were randomly administered in the HD 2000 GISL trial. Bone marrow mononuclear cells (BMMCs) stained with anti-CD34 antibody and Annexin V, were evaluated by flow cytometry before starting chemotherapy, 30 days after completing chemotherapy and after 6 months. Results are expressed as the percentages of BMMCs positive to anti-CD34, to Annexin V or to both. Fourteen patients treated with ABVD, 11 with COPPEBVCAD and 13 with BEACOPP were evaluated before and 30 days after treatment. Late assessments were made in 6, 7 and 8 of them, respectively. No differences were found among the pretherapeutic flow cytometry findings in relation to the staging characteristics (marrow involvement included). All the regimens increased the apoptotic fraction of the whole mononuclear bone marrow cells (COPPEBVCAD did so significantly) and increased the CD34+ compartment (with significant early differences after ABVD and BEACOPP, tending to late persistence for ABVD, only). All the regimens increased the apoptotic CD34+ cells within the whole BMMC population (significantly after BEACOPP), although with a general trend to decrease in their percentage within the CD34+ compartment over time, even after the most dose-dense regimens. Based on the variations induced in the apoptotic fraction of all mononuclear and CD34+ cells, ABVD was the least toxic regimen and COPPEBVCAD the most toxic one.

The feasibility and safety of stem cell-based therapy with expanded adipose-derived stem cells (ASCs) has been investigated in a phase I clinical trial. The present study was designed as a phase II multicenter, randomized controlled trial to further investigate the effectiveness and safety of ASCs in the treatment of complex perianal fistulas.

Serial cardiac magnetic resonance imaging (CMR) is the reference standard for evaluating left ventricular function, wall motion, and infarct size in patients with acute myocardial infarction, as well as remodeling during follow-up. The cardiac CMR substudy of the randomized multicenter REPAIR-AMI trial (Reinfusion of Enriched Progenitor cells And Infarct Remodeling in Acute Myocardial Infarction study) aimed at gaining insight into postinfarction left ventricular remodeling processes.

Successful treatment of acute myeloid leukemia (AML) remains a therapeutic challenge, with a high percentage of patients suffering from persistent or relapsed disease. Resistance to drug therapy can develop from increased drug export and/or altered intracellular signaling. Both mechanisms are mediated by the efflux transporters ABCC4 (MRP4), ABCC5 (MRP5), and ABCC11 (MRP8), which are involved in cellular efflux of endogenous signaling molecules (e.g., cyclic adenosine 3', 5'-monophosphate and cyclic guanosine 3',5'-monophosphate) and nucleoside analogues. The nucleoside analogue cytosine arabinoside (AraC) is administered to all patients with AML.

NDRG (N-Myc downstream-regulated gene)-2 is a member of the NDRG family. Although it has been suggested that NDRG2 is involved in cellular differentiation and tumor suppression, its intracellular signal and regulatory mechanism are not well known. Here, we show the differential expression of NDRG2 in human colon carcinoma cell lines and tissues by reverse transcription-polymerase chain reaction and immunohistochemical analyses with monoclonal antibody against NDRG2. NDRG2 was strongly expressed in normal colonic mucosa and colonic adenomatous tissues (25 of 25) but not in all invasive cancer tissues [44 of 99 (44%)]. Most distinctive results indicated that the high expression level of NDRG2 has a positive correlation with tumor differentiation and inverse correlation with tumor invasion depth and Dukes' stage of colon adenocarcinoma. To investigate the roles of NDRG2 in tumorigenesis, we used in vitro cell culture system. SW620 colon cancer cell line with a low level of intrinsic NDRG2 protein was transfected with NDRG2-expressing plasmid. TOPflash luciferase reporter assay showed that the transcriptional activity of T-cell factor (TCF)/lymphoid enhancer factor (LEF) was reduced by NDRG2 introduction, but not by the introduction of mutant NDRG2 generated by deletion or site-directed mutagenesis. Intracellular beta-catenin levels were slightly reduced in the NDRG2-transfected SW620 cells and this regulation of beta-catenin stability and TCF/LEF activity were mediated through the modulation of glycogen synthase kinase-3beta activity by NDRG2 function. Our results suggest that NDRG2 might play a pivotal role as a potent tumor suppressor by the attenuation of TCF/beta-catenin signaling for the maintenance of healthy colon tissues.

Comparison of intracoronary infusion of bone marrow (BM)-derived unselected mononuclear cells (UNSEL) and selected CD34(+)CXCR4(+) cells (SEL) in patients with acute myocardial infarction (AMI) and reduced <40% left ventricular ejection fraction (LVEF).

Prior studies showed that immune inhibitory CD34(+) progenitor cells, whose numbers are increased in head and neck squamous cell carcinoma (HNSCC) patients, can be differentiated into immune stimulatory dendritic cells by culture with 1alpha,25-dihydroxyvitamin D(3) (1,25[OH](2)D(3)). This was extended to a pilot study to diminish intratumoral levels of CD34(+) progenitor cells by inducing their maturation into dendritic cells with 1,25(OH)(2)D(3).

The efficacy of pegfilgrastim+/-chemotherapy for mobilizing stem cells in patients with solid tumours was assessed. In cycle 0, a 14-day prechemotherapy cycle, patients (N=61) were randomized open-label to single doses of pegfilgrastim (6, 12 or 18 mg) on day 1, or daily filgrastim (10 microg/kg) for < or =7 days. Mean peak peripheral CD34+ cell counts increased with pegfilgrastim dose, but were significantly higher than filgrastim only at the 18 mg dose (10.17 vs 4.96 x 10(4)/ml; P=0.014). In the clinically relevant period of days 3-7, both 12 and 18 mg pegfilgrastim doses produced significantly higher peak CD34+ counts (8.18 and 9.96 vs 4.51 x 10(4)/ml for filgrastim; P=0.034 and 0.006). In cycle 1, patients received carboplatin/paclitaxel on day 1, followed from day 2 by pegfilgrastim 6-18 mg or daily filgrastim (5 microg/kg/day for < or =14 days) as per randomization in cycle 0. There were no significant differences in mean peak CD34+ count between pegfilgrastim and filgrastim, but there was an advantage for pegfilgrastim 18 mg in the relevant period of days 7-12 (3.14 vs 1.19 x 10(4)/ml; P=0.043). A single pegfilgrastim dose (> or =6 mg) could be substituted for daily filgrastim in cytokine-only peripheral CD34+ cell mobilization.

Endothelial progenitor cells maintain endothelium integrity by replacing injured endothelial cells. Cholesterol-lowering promotes either endothelial progenitor cells mobilization or improves endothelial function. It is unknown whether improving endothelial function with statin is associated with a parallel increased endothelial progenitor cells availability. Thirty-two hypercholesterolemic patients were assigned to 4-week rosuvastatin (10 mg daily) and 16 hypercholesterolemic served as controls. Circulating endothelial progenitor cells, brachial artery flow-mediated vasodilatation, an index of endothelial function, and the lipid profile were measured before and after the 4-week statin therapy. At baseline, we found a correlation between circulating endothelial progenitor cells and flow-mediated vasodilatation (r = .31, P = .029). At the end of the 4-week intervention with rosuvastatin there was a 37% reduction in low-density lipoprotein cholesterol (P < .001) and a significant 72% increase in the number of endothelial progenitor cells and flow-mediated vasodilatation (4.7 + 0.7% to 8.8 + 0.4%, P < .001). Endothelial progenitor cells and flow-mediated vasodilatation were unchanged at the end of the study in patients not taking statin. A correlation emerged between endothelial progenitor cells and flow-mediated vasodilatation variations (r = .52, P < .001), this correlation being still significant after controlling for blood cholesterol reduction. In conclusion, short-term rosuvastatin therapy contributes in hyperchoelsterolemic patients to improving endothelial function by lowering cholesterol and increasing the number of circulating endothelial progenitor cells; the latter effect appears to be partly independent from reduction in plasma cholesterol.