Objective Assessment of the mobilization of non-hematopoietic very small embryonic-like stem cells (VSEL) in acute myocardial infarction (MI). Background Acute MI induces mobilization of bone marrow stem cells. Recently rare population of VSELs, expressing markers of embryonic pluripotent stem cells (PSC) was identified in adult murine bone marrow and human umbilical cord blood. Methods 31 pts with acute MI and 30 healthy subjects (CTRL) were enrolled. Blood was sampled on admission, after 24 hours and 5 days later. Erythrocytes were lysed and lin-CD45- VSELs were isolated using a live cell sorting system (FACSAria). Results In healthy subjects the median number of circulating VSEL was very low [0.8 (0-1.3] cells/μL. In acute MI VSELs were mobilized early [2.7 (0.2-3.9) cells/μL; p<0.001), and remained elevated after 24 hrs and 5 days [4.7 (0.2-6.4); p<0.003 and 2.6 (0.3-3.6) cells/μL; p<0.03, respectively). The mobilization of VSEL was significantly reduced in patients older than 50 years and with diabetes in comparison to younger and non-diabetic patients. Circulating VSELs were small (7-8 μm) and enriched in mRNA of PSC markers (Oct-4, Nanog), cardiac lineage (GATA-4, Nkx2.5/Csx, MEF2C) and endothelial (VE-cadherin) markers. The presence of PSC markers (Oct-4, SSEA-4) and chemokine receptor CXCR4 in circulating VSELs was confirmed at the protein level by immunofluorescent staining and ImageStream system (ISS) analysis. Conclusion Acute MI induced mobilization of very small embryonic-like stem cells expressing pluripotent markers, early cardiac and endothelial markers and chemokine receptor CXCR4.

URL: http://www.clinicaltrials.gov. Unique identifier: NCT01660581.

Aims Ischaemic heart failure (IHF) patients have a poor prognosis even with current guideline‐derived therapy. Intramyocardial injections of autologous or allogeneic mesenchymal stromal cells might improve cardiac function leading to better clinical outcome. Methods The SCIENCE (Stem Cell therapy in IschEmic Non‐treatable Cardiac diseasE) consortium has initiated a Horizon 2020 funded multicentre phase II study in six European countries. It is a double‐blind, placebo‐controlled trial testing the safety and efficacy of allogeneic Cardiology Stem Cell Centre Adipose‐derived Stromal Cells (CSCC_ASC) from healthy donors or placebo in 138 symptomatic IHF patients. Main inclusion criteria are New York Heart Association class II–III, left ventricular ejection fraction < 45% and N‐terminal pro‐B‐type natriuretic peptide levels > 300 pg/mL. Patients are randomized in a 2:1 pattern to receive intramyocardial injections of either CSCC_ASC or placebo. CSCC_ASC and placebo treatments are prepared centralized at Rigshospitalet in 5 mL vials as an off‐the‐shelf product. Vials are distributed to all clinical partners and stored in nitrogen vapour tanks ready to be used directly after thawing. A total of 100 × 106 CSCC_ASC or placebo are injected directly into viable myocardium in the infarct border zone using the NOGA XP system (BDS, Cordis, Johnson & Johnson, USA). Primary endpoint is a centralized core‐laboratory assessed change in left ventricular end‐systolic volume at 6‐month follow‐up measured by echocardiography. The trial started in January 2017, 58 patients were included and treated until July 2018. Conclusion The SCIENCE trial will provide clinical data on efficacy and safety of intramyocardial cell therapy of allogeneic adipose‐derived stromal cells from healthy donors in patients with IHF.

Excessive intake of food, especially palatable and energy-dense carbohydrates and fats, is largely responsible for the growing incidence of obesity worldwide. Although there are a number of candidate antiobesity drugs, only a few of them have been proven able to inhibit appetite for palatable foods without the concurrent reduction in regular food consumption. In this review, we discuss the interrelationships between homeostatic and hedonic food intake control mechanisms in promoting overeating with palatable foods and assess the potential usefulness of systemically administered pharmaceuticals that impinge on the endogenous cannabinoid, opioid, aminergic, cholinergic, and peptidergic systems in the modification of food preference behavior. Also, certain dietary supplements with the potency to reduce specifically palatable food intake are presented. Based on human and animal studies, we indicate the most promising therapies and agents that influence the effectiveness of appetite-modifying drugs. It should be stressed, however, that most of the data included in our review come from preclinical studies; therefore, further investigations aimed at confirming the effectiveness and safety of the aforementioned medications in the treatment of obese humans are necessary.

The regulatory influence of histamine on wound fibroblast function (viability/metabolic activity or secretion of TGFβ1) is dependent on H1 receptor stimulation. Contrary to wound fibroblasts, these cells express a very low level of H1 receptors when isolated from intact dermis and histamine is unable to modify their metabolic activity.