To identify better cells for the treatment of diabetic critical limb ischemia (CLI) and foot ulcer in a pilot trial.

Critical limb ischemia due to peripheral arterial occlusive disease is associated with a severely increased morbidity and mortality. There is no effective pharmacological therapy available. Injection of autologous bone marrow-derived mononuclear cells (BM-MNC) is a promising therapeutic option in patients with critical limb ischemia, but double-blind, randomized trials are lacking.

Cirrhosis, the end stage of progressive hepatic fibrosis, is characterized by distortion of the hepatic architecture and the formation of regenerative nodules. Liver transplantation is one of the few available therapies for such patients. However, due to a severe shortage of organ donors, surgical complications, transplant rejection and the high cost of this procedure much interest has focused on research to find new treatment modalities for this disease. There is accumulating evidence for the contribution of bone marrow stem cells to participate in liver regeneration.

Cell therapy is a promising novel option for treatment of cardiovascular disease. Because the role of bone marrow-derived circulating progenitor cells (BM-CPCs) after cell therapy is less clear, we analyzed in this randomized, controlled study the influence of intracoronary autologous freshly isolated bone marrow cell transplantation (BMC-Tx) by using a point-of-care system on cardiac function and on the mobilization of BM-CPCs in patients with ischemic heart disease (IHD). Fifty-six patients with IHD were randomized to either receive freshly isolated BMC-Tx or a control group that did not receive cell therapy. Peripheral blood concentrations of CD34/45(+) and CD133/45(+) CPCs were measured by flow cytometry pre-, immediately post-, and at 3, 6, and 12 months postprocedure in both groups. Global ejection fraction and the size of infarct area were determined by left ventriculography. We observed in patients with IHD after intracoronary transplantation of autologous freshly isolated BMCs-Tx at 3 and 12 months follow-up a significant reduction of the size of infarct area and increase of global ejection fraction as well as infarct wall movement velocity. The mobilization of CD34/45(+) and CD133/45(+) BM-CPCs significantly increased at 3, 6, and 12 months after cell therapy when compared with baseline in patients with IHD, although no significant changes were observed between pre- and immediately postintracoronary cell therapy administration. In the control group without cell therapy, there was no significant difference of CD34/45(+) and CD133/45(+) BM-CPCs mobilization between pre- and at 3, 6, and 12 months postcoronary angiography. Intracoronary transplantation of autologous freshly isolated BMCs by using a point-of-care system in patients with IHD may enhance and prolong the mobilization of CD34/45(+) and CD133/45(+) BM-CPCs in peripheral blood and this might increase the regenerative potency in IHD.

There is growing evidence that intracoronary autologous bone marrow cells transplantation (BMCs-Tx) in patients with chronic myocardial infarction beneficially affects postinfarction remodelling. In this randomized controlled study we analyzed the influence of intracoronary autologous freshly isolated bone marrow cells transplantation by use of point of care system on cardiac function and on the functional activity of bone marrow derived circulating progenitor cells (BM-CPCs) in patients with ischemic heart disease (IHD).

Imatinib (400 mg daily) is considered the best initial therapy for patients with newly diagnosed chronic myeloid leukemia (CML) in the chronic phase. However, only a minority of patients treated with imatinib have a complete molecular remission.

For transcoronary progenitor cells' administration, injections under flow arrest (over-the-wire balloon technique, OTW) are used universally despite lack of evidence for being required for cell delivery or being effective in stimulating myocardial engraftment. Flow-mediated endothelial rolling is mandatory for subsequent cell adhesion and extravasation.

To establish a safe dose of subcutaneous (SC) recombinant interleukin 2 (rIL-2) in an outpatient setting for children with stage 4 neuroblastoma after megatherapy (MGT) and autologous stem-cell reinfusion (ASCR) that is able to sustain an increase of natural-killer cells (NKCs) above the level previously reported for immunomodulatory potency.

Previous studies have suggested that mesenchymal stromal cells (MSCs) enhance the engraftment of hematopoietic stem cells and modulate the host's immune response. However, there are no randomized studies to confirm these results. Moreover, there are some concerns about the risk of tumor recurrence because of the immunosuppressive property of MSCs. We conducted an open-label, randomized phase II clinical study to assess the outcome of MSC coinfusion (3-5 × 10(5) cells/kg) during haploidentical hematopoietic stem cell transplantation. From June 2007 to June 2008, a total of 55 patients who were diagnosed with leukemia in complete remission entered the study (27 in the treatment group and 28 in the control group). No immediate or long-term toxic side effects related to MSC infusion were noted, and the median times of white blood cell and platelet engraftment were comparable between the 2 groups. However, within 100 days, the time to a platelet concentration of >50 × 10(9) cells/L was markedly faster in the treatment group compared with the control group (22 days vs. 28 days; P = 0.036). Stromal-derived factor-1α (SDF-1α) reached a peak concentration more rapidly in the treatment group compared with the control group (8th vs. 16th day). The concentrations of SDF-1α, thrombopoietin (TPO), and interleukin-11 were also elevated in the MSC-treated group compared with the control group. The accumulative occurrence rate of acute graft-versus-host disease greater than grade 2 was 51.8% and 38.9% in the treatment and control groups (P = 0.422), respectively, whereas the occurrence rate of chronic graft-versus-host disease was 51.4% and 74.1% (P = 0.261), respectively. Through March 2010, which marked 2 years, the overall survival rate was 69.7% for the MSC-treated group and 64.3% for the control group (P = 0.737). Three patients in the treatment group and 2 patients in the control group experienced a hematological relapse and died of leukemia.

Recent research of lateral elbow tendinopathy has led to the use of laboratory-amplified tenocyte-like cells.

periodontal disease is associated with endothelial dysfunction and increased circulating progenitor cell (CPC) count. This study sought to investigate the effect of periodontal treatment on CPC count and vascular endothelial function.

Although survival of children with acute lymphoblastic leukaemia has improved greatly in the past two decades, the outcome of those who relapse has remained static. We investigated the outcome of children with acute lymphoblastic leukaemia who relapsed on present therapeutic regimens.

Autologous hematopoietic stem cell transplantation (ASCT) is an established treatment for patients with hematologic malignancies, yet the impact of transplanted CD34(+) cell dose on clinical outcomes is unresolved. We conducted post hoc analyses of transplanted CD34(+) cell dose and hematopoietic recovery following ASCT in 438 patients with non-Hodgkin lymphoma (NHL) or multiple myeloma (MM), using data from 2 multicenter phase 3 clinical studies that compared plerixafor plus granulocyte-colony stimulating factor (G-CSF) versus placebo plus G-CSF as stem cell mobilization regimens. Days to engraftment and the proportion of patients who reached predetermined blood count thresholds were compared across 3 CD34(+) cell dose levels: 2-4 × 10(6) cells/kg, 4-6 × 10(6) cells/kg, and >6 × 10(6) cells/kg, regardless of mobilization treatment. Short-term neutrophil and platelet engraftment times were similar regardless of cell dose. A significant linear trend was observed between transplanted CD34(+) cell dose and the proportion of patients with platelet count >150 × 10(9)/L at 100 days (P < .001), 6 months (P = .026), and 12 months (P = .020) in patients with NHL, and at 100 days in patients with MM (P = .004). A linear trend was also observed between transplanted cell dose and the proportion of patients with platelet count >100 × 10(9)/L at 100 days (P < .001) and 6 months (P = .023) in patients with NHL. A higher cell dose was associated with a lower percentage of NHL patients requiring red blood cell transfusions (P = .006). Our analyses confirm previous findings that transplanted CD34(+) cell dose may be associated with better long-term platelet recovery after ASCT.

Endothelial dysfunction is a fundamental step in the atherosclerotic disease process. Activation or injury of the endothelium leads to a variety of inflammatory disorders, including the release of microparticles. Endothelial progenitor cells may contribute to the maintenance of the endothelium by replacing injured mature endothelial cells.

Endothelial progenitor cells (EPCs) contribute to the maintenance of endothelial integrity and function. We investigated the effects of rosuvastatin and allopurinol on the number of EPCs in patients with heart failure and aimed to provide insight into the molecular inflammatory and oxidative mechanisms that could be responsible for the alterations in EPC levels after treatment.

Stimulation of the penetration of topically applied substances into the skin is a topic of intensive dermatological and pharmacological research. Next to intercellular penetration, i.e. a penetration inside the lipid layers around the corneocytes, follicular penetration also represents an efficient penetration pathway. The hair follicles act as a long-term reservoir for topically applied substances. They are surrounded by or contain several important target structures, such as blood capillaries, stem cells and dendritic cells. Therefore, the hair follicles have to be well protected from hazardous substances coming into contact with the skin. The traditional method of decontamination of the skin involves an intensive washing procedure. However, this process represents a massage, which pushes the hazardous substances even deeper into the hair follicles. In the present study, the application of absorbing materials for decontamination of the skin was investigated after the application of a model substance utilizing the tape-stripping procedure. It was found that absorbing materials are better suited than the washing process for decontamination of the skin.

It has been reported that the number of circulating endothelial progenitor cells (EPCs) reflects the endogenous vascular repair ability, with the EPCs pool declining in the presence of cardiovascular risk factors. However, their relationship with hypertension and the effects of anti-hypertensive treatment remain unclear. We randomized 29 patients with mild essential hypertension to receive barnidipine up to 20 mg or hydrochlorothiazide (HCT) up to 25 mg. Circulating EPCs were isolated from peripheral blood at baseline and after 3 and 6 months of treatment. Mononuclear cells were cultured with endothelial basal medium supplemented with EGM SingleQuots. EPCs were identified by positive double staining for both FITC-labeled Ulex europaeus agglutinin I and Dil-labeled acethylated low-density lipoprotein. After 3 and 6 months of treatment, systolic and diastolic blood pressure (BP) were significantly reduced. No difference was observed between drugs. An increase in the number of EPCs was observed after 3 and 6 months of anti-hypertensive treatment (p < 0.05). Barnidipine significantly increased EPCs after 3 and 6 months of treatment, whereas no effect was observed with HCT. No statistically significant correlation was observed between EPCs and clinical BP values. Our data suggest that antihypertensive treatment may increase the number of EPCs. However, we observed a different effect of barnidipine and HCT on EPCs, suggesting that, beyond its BP lowering effect, barnidipine may elicit additional beneficial properties, related to a healthier vasculature.

In the prospective, randomised, double-blind, placebo-controlled Regenerate Vital Myocardium by Vigorous Activation of Bone Marrow Stem Cells (REVIVAL)-2 trial patients with acute myocardial infarction (AMI) and successful mechanical reperfusion received granulocyte-colony stimulating factor (G-CSF, 10 μg/kg KG s.c.) or placebo for 5 days. Aim of this substudy was to assess the impact of G-CSF on systemic inflammatory and procoagulant responses and platelet activation.

Over the last decade, the effects of stem cell therapy on cardiac repair after acute myocardial infarction (AMI) have been investigated with different imaging techniques. We evaluated a new imaging approach using (13)N-ammonia and (18)F-FDG PET for a combined analysis of cardiac perfusion, metabolism, and function in patients treated with intracoronary injection of endothelial progenitors or with conventional therapy for AMI.

To assess the utility of an autologous CD34(+) and CD133(+) stem cells infusion as a possible therapeutic modality in patients with end-stage liver diseases.