1,720,984 research outputs found

    Assessment of ceramic biomaterial effects on the immunological properties of mesenchymal stromal cells employed in advanced therapies for bone regeneration

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    L’osso rappresenta uno dei tessuti maggiormente trapiantati con circa 1 milione di procedure annuali in Europa. Nonostante il trapianto autologo ed allogenico siano caratterizzati da numerosi svantaggi, l’80% dei trapianti d’osso è effettuato tramite queste metodiche. Esistono numerose opportunità di crescita per l’utilizzo di supporti ossei sintetici in associazione con cellule mesenchimali stromali (MSCs) come alternative all’utilizzo di trapianto autologo ed allogenico in campo ortopedico e maxillofaciale. Lo scopo del presente studio è di valutare le proprietà immunomodulatorie di MSCs ottenute da diverse origini, come midollo osseo, tessuto adiposo e sangue cordonale, in associazione con un nuovo biomateriale (HA/TCP) utilizzato come supporto per la somministrazione delle MSCs. La combinazione di MSCs con il supporto non altera il loro fenotipo, gli effetti antiapoptotici e le proprietà immunomodulative. L’elevata espressione di osteocalcina dimostra che la coltura delle MSCs in presenza di HA/TCP per 21 giorni ne determina il differenziamento in senso osteoblastico, anche in assenza di induttori come desametasone o proteine morfogenetiche dell’osso (BMPs). L’aggiunta di BMP-4 promuove la generazione di osteoblasti terminalmente differenziati in MSCs ottenute da midollo osseo, le quali dopo il differenziamento perdono parte delle loro proprietà immunosoppressive nei confronti di linfociti T e cellule NK. Complessivamente, questo studio aumenta la conoscenza della biologia delle MSCs e fornisce dati pre-clinici riguardo l’utilizzo di MSCs allogeniche in combinazione con supporti a base di ceramica nel trattamento di difetti ossei.Bone is among the most frequently transplanted tissue with about 1 million procedures annually in Europe. Despite their considerable disadvantages, allografts and autografts account for more than 80% of total graft volume. Significant growth opportunities exist for synthetic bone grafts in association with mesenchymal stromal cells (MSCs) from autologous or allogeneic sources as alternatives to biological bone grafts in orthopaedic and maxillofacial surgery. Aim of the present project is to assess the immunomodulatory properties of MSCs of different origin, such as bone marrow, adipose tissue and cord blood, in the presence of a novel biomaterial (HA/TCP) used as scaffold for MSC delivery. The association of all MSC types with the biomaterial does not modulate their phenotype, their anti-apoptotic behaviour and immune modulative properties. Gene transcription analysis reveal that the osteoblastic differentiation was induced when MSCs were cultured for up to 21 days in presence of biomaterial, even in absence of inducers such as dexamethasone or bone morphogenetic protein (BMPs). High osteocalcin expression demonstrates that BM-MSCs could differentiate into terminally osteoblasts if treated with BMP-4 and that differentiated BM-MSCs partially loss their immune suppressive behaviour towards T and NK cell proliferation. Overall, this study increases the knowledge on MSC biology and gives pre- clinical data concerning the use of allogeneic MSC in combination with ceramic scaffolds to treat bone defects

    G-CSF displays restricted ability to promote Sca-1(+) cardiac stem cell proliferation in vitro

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    Granulocyte colony-stimulating factor (G-CSF) is a controversial chemical in cardiac cell therapy. Myocardial homing of mobilized bone marrow-derived cells is thought to play a critical role in observed G-CSF-induced cardiac repair; meanwhile, the activation of proliferative potential of cardiac stem cells (CSCs) residing in the heart is a significant challenge. The present study aims to investigate whether G-CSF receptor is expressed in adult resident Sca-1(+) CSCs and determine the effect of G-CSF treatment on the proliferation of CSCs. For cardiac cells isolation, 12-week-old male C57BL/6 mice were anesthetized in a chamber containing 2.5 % isoflurane in oxygen, euthanized by CO2 inhalation and then sacrificed by cervical dislocation. Magnetic-activated cell sorting was employed to acquire highly purified Sca-1(+) CSCs. We found that G-CSF receptor was expressed in adult resident Sca-1(+) CSCs by immunofluorescence staining and Western blotting. Exposure of Sca-1(+) cells to G-CSF in the culture medium for 72 h induced time-dependent but self-limiting cell cycle acceleration with a restricted effect on the CSC proliferation. As a result, it has provided a new insight to focus on the association between cardiac G-CSF therapy and adult resident stem cell activation. It may suggest gaining a deeper insight into the mechanisms of the interaction between CSCs and G-CSF to develop a synergistic strategy based on resident stem cell and G-CSF therapy for heart disease

    Adipose-derived stromal cells (ASCs)

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    Adipose-derived stromal cells (ASCs) are now emerging as a good alternative to bone marrow derived mesenchymal stromal cells (BM-MSC) for cellular therapy. Similarly to BM-MSC, ASCs can be easily isolated as adherent fibroblastoid cell population after processing lipoaspirate samples. Lipoaspiration provides a great number of cells, without extensive manipulation. ASCs express classical mesenchymal markers and only at early passages express CD34. ASCs can differentiate in cells of mesodermal lineages, such as adipocytes, osteocytes and condrocytes. ASCs share with BM-MSC the same ability to inhibit the proliferation of allogeneic, activated immune cells, thus affecting in vivo in animal models the onset and course of rheumatoid arthritis (RA), experimental autoimmune encephalomyelitis (EAE), Crohn’s disease (CD), ulcerous colitis (UC) and graft-versus-host disease (GvHD). On the other hand, the main molecular pathway involved in this effect is still unclear. On the basis of this functional property, ASCs are used in different clinical trials to treat RA, CD, UC and GvHD. However, the most promising field of clinical application is represented by bone defect repair. Despite the ability to regenerate injured tissues and to block the progression of inflammatory disorders, some authors reported that ASCs can also induce, in in vivo animal models, the growth and vascularization of solid and hematological tumors. Conversely, ASCs have been shown to hamper tumor cell proliferation, reduce cell viability and induce necrosis. Thus, more accurate studies, collaborative protocols, high standardization of methods, and safety controls are required to exclude transformation of transplanted ASCs

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Author Index

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    Chapter 4: Mesenchymal stem cell isolation and expansion methodology. In: Stem Cells And Cancer Stem Cells: Therapeutic Applications in Disease and Injury

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    Mesenchymal stem cells (MSCs) are adult non-hematopoietic stem cells originally isolated from bone marrow (BM) (Prockop, 1997), but they are virtually present and can be isolated from almost every tissue of the body (Da Silva et al., 2006), including peripheral blood (Roufosse et al., 2004). This evidence suggests that MSCs could be part of a mesenchymal-stromal cell system diffused throughout the body. The real in vivo counterpart of cultureexpanded MSCs is still unknown; however, different Authors suggested that MSCs are a subgroup of vessel-lining pericytes that may contribute to vessel homeostasis by reacting to tissue damage with regenerative processes, locally modulating the inflammatory reaction, and entering systemic circulation to migrate according to cytokine gradients (Crisan et al., 2008). The International Society of Cellular Therapy (ISCT) stated the following three criteria for the definition of MSCs after in vitro expansion (Dominici et al., 2006): (1) the adherence to plastic under standard tissue culture conditions; (2) the expression of a specific combination of cell surface markers; (3) the capability of multilineage differentiation under appropriate in vitro conditions. These criteria are necessary to overcome the problems due to the absence of MSCspecific cell surface markers, the high heterogeneity in terms of differentiation potential, and the similarities to fibroblasts displayed by isolated and expanded MSCs. Consequently, ISTC suggested to define MSCs as “Multipotent Mesenchymal Stromal Cells” instead of “Mesenchymal Stem Cells”. In this Chapter, MSC isolation, expansion and functional characterization will be discussed in details
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