New perspectives to repair a broken heart

The aim of cardiac cell therapy is to restore at least in part the functionality of the diseased or injured myocardium by the use of stem/ progenitor cells. Recent clinical trials have shown the safety of cardiac cell therapy and encouraging efficacy results. A surprisingly wide range of non-myogenic cell types improves ventricular function, suggesting that benefits may result in part from mechanisms that are distinct from true myocardial regeneration. While clinical trials explore cells derived from skeletal muscle and bone marrow, basic researchers are investigating sources of new cardiomyogenic cells, such as resident myocardial progenitors and embryonic stem cells. In this commentary we briefly review the evolution of cell-based cardiac repair, some progress that has been made toward this goal, and future perspectives in the regeneration of cardiac tissue. © 2009 Bentham Science Publishers Ltd

Bone marrow-derived cells can acquire cardiac stem cells properties in damaged heart

Experimental data suggest that cell-based therapies may be useful for cardiac regeneration following ischaemic heart disease. Bone marrow (BM) cells have been reported to contribute to tissue repair after myocardial infarction (MI) by a variety of humoural and cellular mechanisms. However, there is no direct evidence, so far, that BM cells can generate cardiac stem cells (CSCs). To investigate whether BM cells contribute to repopulate the Kit+ CSCs pool, we transplanted BM cells from transgenic mice, expressing green fluorescent protein under the control of Kit regulatory elements, into wild-type irradiated recipients. Following haematological reconstitution and MI, CSCs were cultured from cardiac explants to generate 'cardiospheres', a microtissue normally originating in vitro from CSCs. These were all green fluorescent (i.e. BM derived) and contained cells capable of initiating differentiation into cells expressing the cardiac marker Nkx2.5. These findings indicate that, at least in conditions of local acute cardiac damage, BM cells can home into the heart and give rise to cells that share properties of resident Kit+ CSCs

Serum and supplement optimization for EU GMP-compliance in cardiospheres cell culture

Cardiac progenitor cells (CPCs) isolated as cardiospheres (CSs) and CS-derived cells (CDCs) are a promising tool for cardiac cell therapy in heart failure patients, having CDCs already been used in a phase I/II clinical trial. Culture standardization according to Good Manufacturing Practices (GMPs) is a mandatory step for clinical translation. One of the main issues raised is the use of xenogenic additives (e.g. FBS, foetal bovine serum) in cell culture media, which carries the risk of contamination with infectious viral/prion agents, and the possible induction of immunizing effects in the final recipient. In this study, B27 supplement and sera requirements to comply with European GMPs were investigated in CSs and CDCs cultures, in terms of process yield/efficiency and final cell product gene expression levels, as well as phenotype. B27- free CS cultures produced a significantly reduced yield and a 10-fold drop in c-kit expression levels versus B27+ media. Moreover, autologous human serum (aHS) and two different commercially available GMP AB HSs were compared with standard research-grade FBS. CPCs from all HSs explants had reduced growth rate, assumed a senescent-like morphology with time in culture, and/or displayed a significant shift towards the endothelial phenotype. Among three different GMP gamma-irradiated FBSs (giFBSs) tested, two provided unsatisfactory cell yields, while one performed optimally, in terms of CPCs yield/phenotype. In conclusion, the use of HSs for the isolation and expansion of CSs/CDCs has to be excluded because of altered proliferation and/or commitment, while media supplemented with B27 and the selected giFBS allows successful EU GMP-complying CPCs culture

Dal team accoglienza al bed management ospedaliero.

RIASSUNTOLa riduzione dei posti letto negli ospedali laziali, ha ri-disegnato il concetto di servizio sanitario ospedaliero regionale, riconoscendo l'ospedale il solo luogo dove recarsi per curare le malattie acute ed urgenti. L'Azienda Ospedaliera San Camillo-Forlanini di Roma, nel rispetto del piano sanitario regionale, del piano di rientro e della riqualificazione della rete ospedaliera, ha avuto una significativa riduzione di posti letto e ciò, ha comportato una riorganizzazione interna. La Direzione Aziendale per dare una risposta soddisfacente all'utenza, ha dato inizio nel febbraio del 2008 ad un progetto, oggi servizio, con l'istituzione di un gruppo di coordinatori infermieristici, con lo specifico mandato di razionalizzare ed ottimizzare i posti letto dedicati all'emergenza-urgenza. Questo gruppo denominato "Team Accoglienza" è formato da caposala esperti, che conoscono il funzionamento dell'intero ospedale. Il team collabora, quotidianamente, con il personale medico ed infermieristico del Pronto Soccorso, per la definizione del percorso diagnostico, terapeutico ed assistenziale più idoneo al malato. Il progetto è stato sviluppato applicando la metodologia: del Percorso di Massima di Riferimento e l'Analisi Sistemica. Negli anni questo servizio ha contribuito: al miglioramento di alcuni indicatori sistemici di attivití , di alcune Unití  Operative ed alla formazione di personale sanitario di direzione. Nel 2009 la Giunta Regionale del Lazio ha riconosciuto tale progetto come strategico all'interno delle organizzazioni ospedaliere pubbliche e private.Parole Chiave: Bed Manager, ricovero, ottimizzatore.ABSTRACTReduction on number of hospital beds i.e. on patients' admission among hospitals in Lazio has lead to a reformulation of health service framework within Lazio indentifying hospital as the only place to go to treat acute and urgent diseases. San Camillo-Forlanini, the largest hospital in Rome, according to the regional health plan, the recovery plan and the redevelopment of network hospital has had a significant reduction of hospital beds leading, as consequence, to the need of an internal reorganization. In order to correctly address this issue, the management of the Hospital started in February 2008 a project, setting up a group made up by nursing coordinators which had as a main aim to manage the number of hospital beds needed for emergencies. This group has been called "Admission Team" and nurses within the group are familiar with hospital policies and organization. The team collaborates daily with physicians and nurses in emergency room, in order to decide the most appropriate health care protocol for each patient. The project follows a specific methodology i.e. Systemic Analysis. Over the years this project has contributed to the improvement to a number of indicators and more generally to the health care within the hospital together with the enhancement of education of new managerial roles among health professional. In 2009, the Regional Council of Lazio has recognized this project as strategic within private and public hospitals. Keywords: Bed Management, admission, hospital polic

Autonomous Mower Saves Energy and Improves Quality of Tall Fescue Lawn

Battery-powered autonomous mowers are designed to reduce the need of labor for lawn mowing compared with traditional endothermic engine mowers and at the same time to abate local emissions and noise. The aim of this research was to compare autonomous mower with traditional rotary mower on a tall fescue (Festuca arundinacea) lawn under different nitrogen (N) rates. A two-way factor experimental design with three replications was adopted. In the study, fourNrates (0, 50, 100, and 150 kghaL1) and two mowing systems (autonomous mower vs. gasolinepowered walk-behind rotary mower equipped for mulching) were used. As expected, N fertilization increased turf quality. At the end of the trial, the autonomous mower increased turf density (3.2 shoots/cm2) compared with the rotary mower (2.1 shoots/cm2) and decreased average leaf width (2.1 mm) compared with the rotary mower (2.7 mm). Increased density and decreased leaf width with autonomous mowing yielded higher quality turf (7.3) compared with the rotary mower (6.4) and a lower weed incidence (6% and 9% cover for autonomous mower and rotary mower, respectively). Disease incidence and mowing quality were unaffected by the mowing system. The autonomous mower working time was set to 10 hours per day (7.8 hours for mowing and 2.2 hours for recharging) for a surface of 1296 m2. The traditional rotary mower working time for the same surface was 1.02 hours per week. The estimated primary energy consumption for autonomous mower was about 4.80 kWh/week compared with 12.60 kWh/week for gasoline-powered rotary mowing. Based on turf quality aspects and energy consumption, the use of autonomous mowers could be a promising alternative to traditional mowers

When Stiffness Matters: Mechanosensing in Heart Development and Disease

During embryonic morphogenesis, the heart undergoes a complex series of cellular phenotypic maturations (e.g. transition of myocytes from proliferative to quiescent or maturation of the contractile apparatus), and this involves stiffening of the extracellular matrix acting in concert with morphogenetic signals. The maladaptive remodelling of the myocardium, one of the processes involved in determination of heart failure, also involve mechanical cues, with a progressive stiffening of the tissue that produces cellular mechanical damage, inflammation and ultimately myocardial fibrosis. The assessment of the biomechanical dependence of the molecular machinery (in myocardial and non-myocardial cells) is therefore essential to contextualize the maturation of the cardiac tissue at early stages and understand its pathologic evolution in ageing. Since systems to perform multiscale modelling of cellular and tissue mechanics have been developed, it appears particularly novel to design integrated mechano-molecular models of heart development and disease to be tested in ex vivo reconstituted cells/tissue-mimicking conditions. In the present contribution, we will discuss the latest implication of mechanosensing in heart development and pathology, describe the most recent models of cell/tissue mechanics and delineate novel strategies to target the consequences of heart failure with personalized approaches based on tissue engineering and induced pluripotent stem cells (iPSCs) technologies

Biocompatibility and Connectivity of Semiconductor Nanostructures for Cardiac Tissue Engineering Applications

Nano- or microdevices, enabling simultaneous, long-term, multisite, cellular recording and stimulation from many excitable cells, are expected to make a strategic turn in basic and applied cardiology (particularly tissue engineering) and neuroscience. We propose an innovative approach aiming to elicit bioelectrical information from the cell membrane using an integrated circuit (IC) bearing a coating of nanowires on the chip surface. Nanowires grow directly on the backend of the ICs, thus allowing on-site amplification of bioelectric signals with uniform and controlled morphology and growth of the NWs on templates. To implement this technology, we evaluated the biocompatibility of silicon and zinc oxide nanowires (NWs), used as a seeding substrate for cells in culture, on two different primary cell lines. Human cardiac stromal cells were used to evaluate the effects of ZnO NWs of different lengths on cell behavior, morphology and growth, while BV-2 microglial-like cells and GH4-C1 neuroendocrine-like cell lines were used to evaluate cell membrane–NW interaction and contact when cultured on Si NWs. As the optimization of the contact between integrated microelectronics circuits and cellular membranes represents a long-standing issue, our technological approach may lay the basis for a new era of devices exploiting the microelectronics’ sensitivity and “smartness” to both improve investigation of biological systems and to develop suitable NW-based systems available for tissue engineering and regenerative medicine

Cardiac cell therapy: the next (re)generation

Heart failure remains one of the main causes of morbidity and mortality in the Western world. Current therapies for myocardial infarction are mostly aimed at blocking the progression of the disease, preventing detrimental cardiac remodeling and potentiating the function of the surviving tissue. In the last decade, great interest has arisen from the possibility to regenerate lost tissue by using cells as a therapeutic tool. Different cell types have been tested in animal models, including bone marrow-derived cells, myoblasts, endogenous cardiac stem cells, embryonic cells and induced pluripotent stem cells. After the conflicting and often inconsistent results of the first clinical trials, a step backward needs to be performed, to understand the basic biological mechanisms underlying spontaneous and induced cardiac regeneration. Current studies aim at finding new strategies to enhance cellular homing, survival and differentiation in order to improve the overall outcome of cellular cardiomyoplasty