1,720,962 research outputs found
Standardization of immune quality controls on clinical-grade mesenchymal stromal cells of different origin produced according to GMP rules
No full textLa versatile ed ampia applicazione delle Cellule Stromali Mesenchimali (MSC) per diverse applicazioni cliniche ha generato negli ultimi anni un grande e crescente interesse per utilizzo clinico delle MSC come terapia cellulare. La ricerca sulla biologia cellulare delle MSC e’ in continuo sviluppo, come dimostrato dal crescente numero di trial clinici basati sull’utilizzo clinico di MSC. Alcuni di questi trials sfruttano la capacita’ immunosoppressiva delle MSC per la cura di patologie come la GvHD e la sclerosi multipla. Le MSC esercitano un’azione immunosoppressiva potenzialmente diretta contro tutte le cellule del sistema immunitario. Di conseguenza, per quantificare le capacita' immunosoppressive di MSC espanse in accordo a regole GMP da diversi laboratori, e’ di fondamentale importanza sviluppare test in vitro altamente standardizzati e riproducibili, senza i quali non sarebbe possibile ottenere risultati comparabili e riproducibili tra diversi gruppi di ricerca. Scopo del lavoro e’ stato quello di comparare le capacita’ immunoregolatorie di tre diversi tipi di MSC (espanse in accordo a regole GMP) in due laboratori indipendenti (Stem Cell Research Laboratory of the University of Verona and the INSERM Institute in Rennes, France).
La standardizzazione di test funzionali ha permesso di dimostrare che MSC “resting” sono in grado di inibire la proliferazione di cellule T ed NK ma non di cellule B. MSC da tessuto adiposo coltivate in lisato piastrinico (ADSC-PL) hanno mostrato la piu’ forte immunosoppressione nei confronti di cellule T, tramite l’attivita’, INF- γ dipendente, dell’enzima indoleamina 2,3 diossigenasi. Le MSC non sono in grado di evocare una proliferazione di cellule T allogeniche, ma vengo efficacemente lisate da cellule NK attivate. L’applicazione sistematica di test quantitativi e riproducibili ha messo in evidenza differenti proprieta’ immunologiche delle MSC prodotte secondo differenti protocolli di espansione GMP. Tra le cellule testate, le ADSC-PL emergono come le piu’ promettenti per l’utilizzo in futuri trials clinici.The versatile and wide range application of Mesenchymal Stromal Cells (MSC) for a diverse set of clinical indications has generated a great and increasing interest in MSC as potential therapeutic agents during last years. Research on MSC biology is progressing rapidly, as illustrated by the growing number of clinical trials using MSC. Some of them are taking advance of the immunosuppressive ability of MSC to treat some immunological based disease like GvHD or Multiple Sclerosis. MSC exhibit a wide range of immunosuppressive properties that target virtually any cell of the immune system and these properties can be easily affected and hampered by culture conditions. Therefore, to assess the immunological properties of clinical-grade MSC obtained from different laboratories it is crucial to design fully standardized and reproducible in vitro assays; otherwise, only not comparable, and frequent contradictory results could be achieved.
We aimed to compare immune modulatory properties of clinical-grade MSC using a combination of fully standardized in vitro assays. BMMSC expanded with FCS (BMMSC-FCS) or PL (BMMSC-PL), and ADSC-PL were analyzed in parallel in two independent laboratories (Stem Cell Research Laboratory of the University of Verona and the INSERM Institute in Rennes, France). Standardized functional assays revealed that resting MSC inhibited proliferation of T and NK cells, but not B cells. ADSC-PL were the most potent in inhibiting T-cell growth, a property ascribed to IFN-γ-dependent indoleamine 2,3-dioxygenase activity. MSC did not stimulate allogeneic T cell proliferation but were efficiently lysed by activated NK cells. The systematic use of quantitative and reproducible validation techniques highlights differences in immunological properties of MSC produced using various clinical-grade processes. Among all cell tested, ADSC-PL emerge as the best promising candidate for future clinical trials
Adipose-derived stromal cells (ASCs)
No full textAdipose-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
Immunological properties of embryonic and adult stem cells
No full textThe possibility of treating degenerative diseases by stem cell-based approaches is a promising therapeutical option. Among major concerns for the clinical application of stem cells, some derive from the possibility that stem cells may be rejected by the immune system as a consequence of histoincompatibility and that stem cells themselves may interfere with the normal functions of host immune response. Therefore, the immunogenicity and the immunomodulatory properties of stem cells must be carefully addressed. Although these properties are common features of different stem cell types, some peculiarities can be recognized and characterized for their proper clinical use
Chapter 4: Mesenchymal stem cell isolation and expansion methodology. In: Stem Cells And Cancer Stem Cells: Therapeutic Applications in Disease and Injury
No full textMesenchymal 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
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
Full text linkWe 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
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