Transplantation of circulating progenitor cells (CPC) improves left ventricular function after successful recanalisation of chronic total occlusions at short-term follow-up. Cardiac magnetic resonance imaging (CMRI) is an excellent tool for serial assessment of underlying structural changes in perfusion, left ventricular function, and infarct size.

Glioblastomas are notorious for resistance to therapy, which has been attributed to DNA-repair proficiency, a multitude of deregulated molecular pathways, and, more recently, to the particular biologic behavior of tumor stem-like cells. Here, we aimed to identify molecular profiles specific for treatment resistance to the current standard of care of concomitant chemoradiotherapy with the alkylating agent temozolomide.

Liver failure is the major cause of death in alcoholic steatohepatitis (ASH). In experimental hepatitis, granulocyte-colony stimulating factor (G-CSF) mobilizes hematopoietic stem cells, induces liver regeneration, and improves survival. We studied the short-term effects of G-CSF on CD34+ stem cell mobilization, liver cell proliferation, and liver function in patients with ASH. Twenty-four patients (mean age 54 years) with alcoholic cirrhosis [Child-Turcotte-Pugh score 10 (7-12)] and concomitant biopsy-proven ASH [Maddrey score 36 (21-60)] were randomized to standard care associated with 5 days of G-CSF (10 microg/kg/day, group A, n = 13) or standard care alone (group B, n = 11). Serial measurement of CD34+ cells, liver tests, cytokines [hepatocyte growth factor (HGF); tumor necrosis factor alpha; tumor necrosis factor-R1; interleukin-6; alfa-fetoprotein], and (13)C-aminopyrine breath tests were performed. Proliferating hepatic progenitor cells [HPC; double immunostaining (Ki67/cytokeratin 7)], histology, and neutrophils were assessed on baseline and day 7 biopsies. Abstinent alcoholic patients with cirrhosis served as controls for immunohistochemistry. G-CSF was well tolerated. At day 7, both CD34+ cells (+747% versus -6%, P < 0.003), and HGF (+212% versus -7%, P < 0.03) increased in group A but not in group B. Cytokines and aminopyrine breath test changes were similar between groups. On repeat biopsy, a >50% increase in proliferating HPC was more frequent in group A than in group B (11 versus 2, P < 0.003). Changes in Ki67+/cytokeratin 7+ cells correlated with changes in CD34+ cells (r = 0.65, P < 0.03). Neutrophils and histological changes were similar in both groups.

In vitro studies have demonstrated a 27% increased efficacy of lenograstim over filgrastim. However, equal doses of 10 microg/kg/day of filgrastim and lenograstim have been recommended for mobilization of CD34+ cells without associated chemotherapy. In this study, we investigated whether a 25% reduced dose of lenograstim at 7.5 microg/kg/day is equavalent to 10 microg/kg/day filgrastim for autologous peripheral blood stem cell (PBSC) mobilization and transplantation. A total of 40 consecutive patients were randomized to either filgrastim (n = 20) or lenograstim (n = 20). The two cohorts were similar in regard to disease, sex, body weight, body surface area, conditioning regimens, previous chemotherapy cycles and radiotherapy. Each growth factor was administered for 4 consecutive days. The first PBSC apheresis was done on the 5th day. In the posttransplant period, the same G-CSF was given at 5 microg/kg/day until leukocyte engraftment. Successful mobilization was achieved in 95% of patients. Successful mobilization with the first apheresis, was achieved in 10/20 (50%) patients in the filgrastim group versus 9/20 (46%) patients in the lenograstim group. No significant difference was seen in the median number of CD34+cells mobilized, as well as the median number of apheresis, median volume of apheresis, percentage of CD34+ cells, and CD34+ cell number. Leukocyte and platelet engraftments, the number of days requiring G-CSF and parenteral antibiotics, the number of transfusions were similar in both groups in the posttransplant period. Lenograstim 7.5 microg/kg/day is as efficious as filgrastim 10 microg/kg/day for autologous PBSC mobilization and transplantation.

Cytokine-mobilized PBPC transplants result in rapid neutrophil and platelet engraftment following high-dose chemotherapy. A total of 61 patients with solid tumours, sensitive to carboplatin and paclitaxol, were recruited as part of a phase I/II study and randomized to receive a single dose of 6, 12 or 18 mg pegfilgrastim on day 1 of a 14-day prechemotherapy cycle or daily filgrastim (10 microg/kg) for up to 7 days. The kinetics of megakaryocyte progenitor mobilization were studied using immunohistochemical assays and flow cytometry in a subset of 31 patients. There was no significant difference among treatment groups with respect to the timing of total progenitor colony-forming units (CFUs) and megakaryocyte progenitor (CFU-MK) mobilization, with the highest median peak falling on day 4/5 in all groups. In the pegfilgrastim 18 mg group, the mean peak total CFUs and CFU-MK were statistically significantly higher than in the filgrastim group (2.031x10(4) vs 8.06x10(3) per millilitre, P=0.024 and 1.12x10(4) vs 4.56x10(3) per millilitre, P=0.024, respectively). The kinetic profiles generated using immunohistochemical assays for CFU-MK and FACS analysis for CD41a were closely correlated suggesting that CD41a can be used as a surrogate marker for megakaryocytic mobilization.

Endothelial Progenitor Cells (EPCs) are a specific subtype of haematopoietic stem cells that contribute to the repair of injured endothelium. Treatment with atorvastatin has been shown to increase EPC counts in patients with stable coronary artery disease. Numbers of circulating EPCs decrease in various inflammatory diseases. Thus, we hypothesized that short term statin pre-treatment may alter the acute change in EPC levels during systemic inflammation.

The increasing application of multi-color flow cytometry assays for staging and follow-up in mantle cell lymphoma necessitates that the specificity and sensitivity of this technique are evaluated. Data from prospective clinical trials comparing the clinical applicability of flow cytometry to routine diagnostic methods and to polymerase chain reaction are currently lacking.

Even after recanalization of a chronic total coronary occlusion, functional recovery is incomplete and parts of the myocardium remain hypoperfused. In this randomized, placebo-controlled, and double-blinded study, we investigated relative changes in myocardial perfusion and glucose metabolism induced by intracoronary administration of blood-derived circulating progenitor cells (CPCs), compared with the natural course in a control group after recanalization of total coronary occlusion.

Bone marrow (BM) cells may interact with coronary endothelium and modulate coronary atherosclerosis. We investigated the time course of coronary luminal loss and changes in conductance after intracoronary injection of enriched hematopoietic BM stem cells in patients with previous myocardial infarction (MI). Among 24 patients with acute MI, 13 were randomized to early (<7 days) and 11 to late (4 months) intracoronary injection of CD133+ cells after the infarction. Segmental quantitative coronary angiography and fractional flow reserve (FFR) measurements of the infarct-related (IR) artery (A) and contralateral artery (control) were performed. In the early group, at 4 months, cumulative luminal loss (LL) of the minimal luminal diameter (MLD) of the IRA distal to the stented segment was -0.39 (-0.51-0.10) mm (p < 0.05 vs. control). There was no further change in LL between 4 and 8 months [-0.09 (-0.26-0.15) mm]. In parallel, FFR decreased at 4 months [-0.16 (-0.26-0.001), p < 0.05 vs. control] but slightly increased from 4 to 8 months follow-up [+0.05 (-0.10-0.09)]. In the late group, LL of the MLD of the IRA distal to the stented segments was -0.12 (-0.47-0.07) mm (NS vs. control) at 4 months and further -0.07 (-0.25-0.05) mm (NS) between 4 and 8 months. At 8 months, the total LL of the MLD in the early and late group was only slightly higher compared to control [-0.34 (-0.48--0.16), -0.36 (-0.69--0.09), and -0.12 (-0.39-0.05) mm, respectively, NS]. Early intracoronary administration of hematopoietic BM stem cells in patients with previous MI is associated with accelerated luminal loss and reduced conductance of the infarct-related artery.

Phase I clinical studies have demonstrated the feasibility of implanting autologous skeletal myoblasts in postinfarction scars. However, they have failed to determine whether this procedure was functionally effective and arrhythmogenic.

Growth factors are frequently used to aid peripheral blood progenitor cell mobilization from bone marrow. This phase 2 study examined the efficacy and safety of pegfilgrastim for mobilizing peripheral blood progenitors cells for autologous transplantation.

Internal tandem duplication (ITD) mutations in the juxtamembrane domain-coding sequence of the Fms-like tyrosine kinase 3 (FLT3) gene have been identified in 30% of acute myeloid leukemia (AML) patients and are associated with a poor prognosis. The kinase inhibitor sorafenib induces growth arrest and apoptosis at much lower concentrations in AML cell lines that harbor FLT3-ITD mutations than in AML cell lines with wild-type FLT3.

Background and objective. We investigated immune recovery in 50 patients given either unmanipulated or CD8-depleted allogeneic peripheral blood stem cells after non-myeloablative conditioning.

Granulocyte-colony-stimulating factor (G-CSF) is used to enhance hematopoietic recovery after autologous stem cell transplantation (ASCT). Recommendations for administration of G-CSF during the engraftment phase of ASCT have recently changed. This study sought to compare the early engraftment profile between groups receiving single-dose versus split-dose lenograstim to enhance engraftment after ASCT.

In this open-label randomized clinical trial, HLA-identical sibling-matched hematopoietic stem cells (HSC) were transplanted (non-MSCs group, n=15) or cotransplanted with mesenchymal stem cells (MSCs) (MSCs group, n=10) in hematologic malignancy patients. The median number of MSCs infused was 3.4 x 10(5) kg(-1) (range, 0.3-15.3 x 10(5) kg(-1)). MSCs infusions were well tolerated. The median time to neutrophil engraftment (absolute neutrophil count >0.5 x 10(9) l(-1)) was 16 days for MSCs group and 15 days for non-MSCs group. The median time to platelet engraftment (platelet count >50 x 10(9) l(-1)) was 30 and 27 days, respectively. Grades II-IV acute graft-versus-host disease (GVHD) was observed respectively, in one (11.1%) and eight (53.3%) evaluable patients. Chronic GVHD was found in one (14.3%) and four (28.6%) evaluable patients. The number of patients who relapsed were six (60.0%) and three (20.0%), and the 3-year disease-free survivals were 30.0 and 66.7%, respectively. Thus cotransplantation of MSCs and HSCs may prevent GVHD, but the relapse rate is obviously higher than the control group. We conclude that use of MSCs must be handled with extreme caution before a large-scale clinical trial is performed.

Autologous stem cell therapy in the field of regenerative veterinary medicine involves harvesting tissue, such as fat, from the patient, isolating the stem and regenerative cells, and administering the cells back to the patient. Autologous adipose-derived stem cell therapy has been commercially available since 2003, and the current study evaluated such therapy in dogs with chronic osteoarthritis of the hip. Dogs treated with adipose-derived stem cell therapy had significantly improved scores for lameness and the compiled scores for lameness, pain, and range of motion compared with control dogs. This is the first randomized, blinded, placebo-controlled clinical trial reporting on the effectiveness of stem cell therapy in dogs.

Preimplantation genetic diagnosis or screening (PGD, PGS) involves embryo biopsy on Day 3. Opting for one- or two-cell biopsy is a balance between the lowest risk for misdiagnosis on the one hand and the highest chance for a pregnancy on the other hand.

Clinical trials demonstrated that granulocyte colony-stimulating factor (G-CSF) administration seems to be safe in patients with acute myocardial infarction but the results about the effectiveness are not so encouraging. The main problem is to distinguish the effects that early revascularization and regenerative therapy have on left ventricular (LV) function. The purpose of our perspective randomized trial is to evaluate the efficacy of G-CSF administration, assessed by improvement of LV ejection fraction by cardiac magnetic resonance imaging (MRI), in patients with acute anterior myocardial infarction undergoing primary percutaneous coronary intervention (PCI) and with evidence of LV dysfunction.

Inflammatory responses after intracoronary injection of autologous mononuclear bone marrow cells (mBMC) are not clarified. The aim of this study was to investigate the influence of intracoronary injection of mBMC on inflammatory mediators in patients with acute myocardial infarction (AMI).

Previous studies have suggested that the lower limb arteriosclerosis obliterans (LASO) could be improved by autologous transplantation of either bone marrow mononuclear cells (BM-MNC) or G-CSF-mobilized peripheral blood mononuclear cells (M-PBMNC). However, the number of patients observed was very limited, and little information is available regarding comparison. The present randomised trial was designed to assess which is the better option. One hundred fifty patients with LASO were randomised to either group A (76 cases implanted with M-PBMNC) or group B (74 cases implanted with BM-MNC), and followed up for 12 weeks. Primary outcomes were safety and efficacy of treatment, based on ankle-brachial index (ABI) and rest pain, and analysis was per protocol. Significant improvement of the main clinical index was observed in both groups after transplantation. No transplantation-related complication was observed in either group. Comparative analysis revealed that at 12 weeks after cell implantation, improvement of ABI (difference 0.06 +/- 0.01; p < 0.0001), skin temperature (difference 0.55 +/- 0.25; p = 0.028), and rest pain (difference -0.57 +/- -0.15;p < 0.0001) was significantly better in groupA patients than group B patients. However, there was no significant difference between two groups for pain-free walking distance, transcutaneous oxygen pressure, ulcers, and rate of lower limb amputation. Autologous transplantation of either M-PBMNC or BM-MNC significantly promotes improvement of limb ischaemia in patients with LASO. Comparative analysis indicated that M-PBMNC should be more practical in comparison with BM-MNC in the treatment of LASO.