stem cell senescence in diabetes forgetting the sweet old memories

Diabetes 2014;63:1841–1843 | DOI: 10.2337/db14-0275 Diabetic cardiomyopathy is identified by a left ventricular dysfunction due to metabolic and cellular abnormalities in the absence of atherosclerosis or hypertension and is one of the leading causes of morbidity and mortality in the diabetic population (1). It is characterized by myocardial necrosis and fibrosis, endothelial dysfunction, and stem cell senescence (2). This latter phenomenon is now considered to be a central mechanism of aging and agerelated pathologies as it has been associated with the reduced ability of tissues to replace lost cells and to repair damage (3,4). In this issue, Vecellio et al. (5) analyzed the intriguing issue of whether stem cells isolated from diabetic hearts have a metabolic memory reminiscen

Pericytes and cardiac stem cells: common features and peculiarities:Common features and peculiarities

Clinical data and basic research indicate that the structural and functional alterations that characterize the evolution of cardiac disease towards heart failure may be, at least in part, reversed. This paradigm shift is due to the accumulation of evidence indicating that, in peculiar settings, cardiomyocytes may be replenished. Moving from the consideration that cardiomyocytes are rapidly withdrawn from the cell cycle after birth, independent laboratories have tested the hypothesis that cardiac resident stem/progenitor cells resided in mammalian hearts and were important for myocardial repair. After almost two decades of intensive investigation, several (but partially overlapping) cardiac resident stem/progenitor cell populations have been identified. These primitive cells are characterized by mesenchymal features, unique properties that distinguish them from mesodermal progenitors residing in other tissues, and heterogeneous embryological origins (that include the neural crest and the epicardium). A further layer of complexity is related to the nature, in vivo localization and properties of mesodermal progenitors residing in adult tissues. Intriguingly, these latter, whose possible perivascular pericyte/mural cell origin has been shown, have been identified in human hearts too. However, their exact anatomical localization, pathophysiological role, and their relationship with cardiac stem/progenitor cells are emerging only recently. Therefore, aim of this review is to discuss the different origin, the distinct nature, and the complementary effect of cardiac stem cells and pericytes supporting regenerative strategies based on the combined use of both myogenic and angiogenic factors

Algorithms for Automatic, Real-Time Tsunami Detection in Sea Level Measurements

Automatic, real-time tsunami detection in sea-level measurements is a main component of a tsunami early warning system (TEWS). Although a great effort has been recently undertaken by the scientific and engineering community in developing new technologies (e.g. satellite altimetry, detectors of low-frequency elastic oscillations associated to a tsunami) capable of increasing the awareness of potential tsunamis in the minimum amount of time, at present direct detection in sea level measurements is still the main mean to confirm their actual generation and propagation, i.e. to upgrade or cancel the rapid initial warning usually given on the sole basis of seismic data. The paper describes the best available algorithms and numerical techniques which can be used for automatic real-time tsunami detection by using sea level measurements. The paper takes into consideration all possible device and locations for the sea level detection

A human neuronal model of Niemann Pick C disease developed from stem cells isolated from patient's skin.

Niemann Pick C (NPC) disease is a neurovisceral lysosomal storage disorder due to mutations in NPC1 or NPC2 genes, characterized by the accumulation of endocytosed unesterified cholesterol, gangliosides and other lipids within the lysosomes/late endosomes. Even if the neurodegeneration is the main feature of the disease, the analysis of the molecular pathways linking the lipid accumulation and cellular damage in the brain has been challenging due to the limited availability of human neuronal models.The aim of this study was to develop a human neuronal model of NPC disease by inducing neuronal differentiation of multipotent adult stem cells (MASC) isolated from NPC patients.Stem cells were isolated from 3 NPC patients and 3 controls both from skin biopsies and previously established skin fibroblast cultures. Cells were induced to differentiate along a neuronal fate adapting methods previously described by Beltrami et al, 2007. The surface immunophenotype of stem cells was analyzed by FACS. Stem cell and neuronal markers expression were evaluated by immunofluorescence. Intracellular accumulation of cholesterol and gangliosides were assessed by filipin staining and immunofluorescence, respectively. A morphometric analysis was performed using a Neurite outgrowth image program.After 3 passages in selective medium, MASC isolated either from skin biopsies or previously established skin fibroblast cultures displayed an antigenic pattern characteristic of mesenchymal stem cells and expressed the stem cell markers Oct-4, Nanog, Sox-2 and nestin. A massive lysosomal accumulation of cholesterol was observed only in cells isolated from NPC patients. After the induction of neural differentiation, remarkable morphologic changes were observed and cells became positive to markers of the neuronal lineage NeuN and MAP2. Differentiated cells from NPC patients displayed characteristic features of NPC disease, they showed intracellular accumulation of unesterified cholesterol and GM2 ganglioside and presented morphological differences with respect to cells derived from healthy donors.In conclusion, we generated a human neuronal model of NPC disease through the induction of differentiation of stem cells obtained from patient's easily accessible sources. The strategy described here may be applied to easily generate human neuronal models of other neurodegenerative diseases

Il trattamento endourologico retrogrado della calcolosi cistinica multirecidivante: caso clinico paradigmatico

Presentiamo un caso clinico di calcolosi cistinica multirecidivante paradigmatico. Il paziente giungeva alla nostra osservazione dopo multipli trattamenti endourologici in altra sede con una situazione litiasica complessa: portatore di nefrostomie bilaterali e di stent ureterale destro venivano evidenziati calcoli multipli renali bilaterali e grosse calicificazioni ureterali, a destra a ridosso dello stent e a sinistra per un tratto di oltre 5 cm. Il trattamento endourologico retrogrado eseguito in più tempi, associato a una adeguata terapia medica per la cistinuria, ha portato a una bonifica completa. Riteniamo che il trattamento endourologico retrogrado rappresenti la modalità più adeguata per risolvere la calcolosi cistinica multirecidivante, al quale deve necessariamente essere associata la terapia farmacologica della cistinuria. Risulta altresi mandatario un trattamento in tempi brevi e una permanenza di eventuali endoprotesi ureterali per il tempo strettamente necessario, allo scopo di evitare calcificazioni degli stessi anche con formazioni litiasiche di ossalato di calcio. Ottenuta la bonifica, è consigliabile che anche i controlli vengano effettuati inizialmente secondo scadenze ravvicinate per poter risolvere eventuali recidive prima che raggiungano dimensioni tali da richiedere trattamenti più complessi

Cardiac Cell Senescence and Redox Signaling

Aging is characterized by a progressive loss of the ability of the organism to cope with stressors and to repair tissue damage. As a result, chronic diseases, including cardiovascular disease, increase their prevalence with aging, underlining the existence of common mechanisms that lead to frailty and age-related diseases. In this frame, the progressive decline of the homeostatic and reparative function of primitive cells has been hypothesized to play a major role in the evolution of cardiac pathology to heart failure. Although initially it was believed that reactive oxygen species (ROS) were produced in an unregulated manner as a byproduct of cellular metabolism, causing macromolecular damage and aging, accumulating evidence indicate the major role played by redox signaling in physiology. Aim of this review is to critically revise evidence linking ROS to cell senescence and aging and to provide evidence of the primary role played by redox signaling, with a particular emphasis on the multifunctional protein APE1/Ref in stem cell biology. Finally, we will discuss evidence supporting the role of redox signaling in cardiovascular cells

Role of microenvironment in glioma invasion: What we learned from in vitro models

The invasion properties of glioblastoma hamper a radical surgery and are responsible for its recurrence. Understanding the invasion mechanisms is thus critical to devise new therapeutic strategies. Therefore, the creation of in vitro models that enable these mechanisms to be studied represents a crucial step. Since in vitro models represent an over-simplification of the in vivo system, in these years it has been attempted to increase the level of complexity of in vitro assays to create models that could better mimic the behaviour of the cells in vivo. These levels of complexity involved: 1. The dimension of the system, moving from two-dimensional to three-dimensional models; 2. The use of microfluidic systems; 3. The use of mixed cultures of tumour cells and cells of the tumour micro-environment in order to mimic the complex cross-talk between tumour cells and their micro-environment; 4. And the source of cells used in an attempt to move from commercial lines to patient-based models. In this review, we will summarize the evidence obtained exploring these different levels of complexity and highlighting advantages and limitations of each system used

House Dust Mite Allergy and the Der p1 Conundrum: A Literature Review and Case Series

The house dustmite (HDM) is globally ubiquitous in human habitats. Thirty-two allergens for Dermatophagoides farinae and 21 for Dermatophagoides pteronyssinus have been detected so far. The present minireview summarizes information about the role of Der p 1 as a key coordinator of the HDM-induced allergic response and reports on a series of Italian patients who are allergic to HDMs. We studied the specific IgE profiles in a population of patients with allergic asthma and rhinitis screened for specific immunotherapy (SIT) for HDMallergies, with the aim of obtaining insights into the pathogenic role of Der p1. Patients co-sensitized to other airborne allergens showed a higher prevalence of asthma (9/12 (75%) vs. 2/7 (29%); p < 0.05) than did HDMmono-sensitized patients. The latter group showed higher Der p1 concentrations than that of the co-sensitized group (p = 0.0360), and a direct correlation between Der p1 and Der p2 (r = 0.93; p = 0.0003) was observed. In conclusion, our study offers insights into the role of Der p1 in a population of patients with allergic rhinitis and asthma who were candidates for SIT. Interestingly, Der p1 positivity was associated with bronchial asthma and co-sensitization