Relaxometric investigations addressing the determination of intracellular water lifetime : a novel tumour biomarker of general applicability

This project has received funding from the European Union’s Horizon 2020 (H2020 Health) research and innovation programme under grant agreement No 668119 (project ‘IDentIFY’). This article is based upon work from COST Action EURELAX, CA15209, supported by COST (European Cooperation in Science and Technology).Peer reviewedPublisher PD

Efficient Route to Label Mesenchymal Stromal Cell-Derived Extracellular Vesicles

Recent research results report that extracellular vesicles (EVs) have a central role in both physiological and pathological processes involving intercellular communication. Herein, a simple EVs labeling procedure based on the metabolic labeling of secreting cells (mesenchymal stroma cells, MSCs) with a fluorescein-containing bio-orthogonal dye is described. This procedure was carried out by incubating cells for 72 h with tetraacetylated N-azidoacetyl-D-mannosamine (Ac4ManNAz), a modified sugar containing an azido group that, upon incorporation on the external surface of the cytoplasmatic cell membrane, is specifically conjugated with cyclooctyne-modified fluorescein isothiocyanate (ADIBOFITC). MSCs released fluorescent EVs did not need any further purification. Finally, cellular uptake and tracking of the fluorescein-labeled EVs were successfully assessed by targeting experiments with MSCs. The method appears of general applicability and it may be very useful opening new horizon on diagnostic and therapeutic protocols exploiting EVs

Lack of Plasma Protein Hemopexin Results in Increased Duodenal Iron Uptake

PURPOSE:The body concentration of iron is regulated by a fine equilibrium between absorption and losses of iron. Iron can be absorbed from diet as inorganic iron or as heme. Hemopexin is an acute phase protein that limits iron access to microorganisms. Moreover, it is the plasma protein with the highest binding affinity for heme and thus it mediates heme-iron recycling. Considering its involvement in iron homeostasis, it was postulated that hemopexin may play a role in the physiological absorption of inorganic iron. METHODS AND RESULTS:Hemopexin-null mice showed elevated iron deposits in enterocytes, associated with higher duodenal H-Ferritin levels and a significant increase in duodenal expression and activity of heme oxygenase. The expression of heme-iron and inorganic iron transporters was normal. The rate of iron absorption was assessed by measuring the amount of (57)Fe retained in tissues from hemopexin-null and wild-type animals after administration of an oral dose of (57)FeSO4 or of (57)Fe-labelled heme. Higher iron retention in the duodenum of hemopexin-null mice was observed as compared with normal mice. Conversely, iron transfer from enterocytes to liver and bone marrow was unaffected in hemopexin-null mice. CONCLUSIONS:The increased iron level in hemopexin-null duodenum can be accounted for by an increased iron uptake by enterocytes and storage in ferritins. These data indicate that the lack of hemopexin under physiological conditions leads to an enhanced duodenal iron uptake thus providing new insights to our understanding of body iron homeostasis