1,720,969 research outputs found
Cholinergic effects mediated by M2 muscarinic receptor in human Schwann-like cells induced from adipose mesenchymal stem cells
No full textSchwann cells (SCs) have an important role in peripheral nerve regeneration but there are several restrictions hindering their clinical application. Adipose derived stem cells (ASCs) feature good properties for cell therapies. When exposed to specific growth factors in vitro, they can acquire a SC-like phenotype (dASCs), expressing key SCs markers. Our group has demonstrated that M2 muscarinic receptor in rat dASCs causes a reversible arrest of cell proliferation, increasing SCs myelinating phenotype. Human dASCs, as rat dASCs, express muscarinic receptors. In the present work we evaluate if M2 muscarinic receptor activation may contribute to human dASCs proliferation, migration and phenotype. M2 selective activation by selective agonist Arecaidine Propargyl Ester (APE) causes a decreased cell proliferation, modulating the expression of genes involved in the proliferation/differentiation (i.e. c-jun and egr2) and several neurotrophic factors. Moreover, M2 selective activation is able to decrease cell migration. Although further analyses are needed to best characterise the role of M2 receptor, these results are the first evidence that its selective activation may have effects also on human dASCs proliferation and migration. This may improve our knowledge of these promising therapeutic cells for potential use in nerve regeneration
Muscarinic receptor in Schwann-like adipose derived stem cells: implications in nerve regeneration.
No full textSchwann Cells (SCs) play a central role in the physiology and in the response of the axon injury. The capacity of SCs to proliferate, to secrete growth factors, to modulate immune response, to migrate and to re-myelinate regenerating nerves have been reported (Jessen et al, 2016). However, SCs present limited clinical application, such as the difficulty in collection and culture and the slow rate of in vitro expansion.
Some papers describe that Adipose-derived stem cells (ASCs) have the ability to differentiate towards SCs phenotype (Schwann-like, dASC) following exposure to suitable culture media (Kingham et al, 2007). dASC, like SCs, express functional receptors for different neurotrasmitters, including muscarinic receptor subtypes (M1-M4) that regulate some physiological events.
In the present work, we have characterised the effects mediated by muscarinic receptors on proliferation and neurotrophic factors (NFs) expression and production
M2 receptor activation controls cell growth, migration and differentiation in adipose-mesenchimal stem cells
No full textThe use of synthetic nerve conduits, in combination with different cell types may represent a promising therapy for the peripheral nerve injuries. The great regenerative capacity of peripheral nervous system (PNS) is due to a permissive environment provided by Schwann cells that proliferate, migrate and release growth factors, either during development or after nerve lesions. Mesenchimal stem cells (MSCs) are an attractive cell source for nerve tissue regeneration. They are able to self-renew and possess multi potent differentiation properties. In particular, adipose MSCs (A-MSCs) appear the most promising source of MSCs. Recent studies have shown that A-MSCs can be differentiated in Schwann-like cells, representing an alternative and reliable source of peripheral glial cells. Acetylcholine (ACh), the main neurotransmitter in central and PNS, has the property to modulate neurite outgrowth and to control Schwann cell proliferation and differentiation. ACh plays important role also in non-neural tissue, but its function in MSC has been poorly investigated. In present work we have characterized the muscarinic cholinergic agonist effects in rat A-MSC and in differentiated Schwann-like derived from A-MSCs. Analysis by RT-PCR, western blot and immunocytochemistry analysis have demonstrated that the A-MSCs express several muscarinic receptor subtypes. MTT analysis and wound healing assay have also demonstrated that the selective activation of M2 receptors caused an inhibition of cell growth and migration of MSCs, indicating the ACh as possible modulator of MSC proliferation and migration. In Schwann cell-like derived from A-MSC, similarly to that observed in Schwann cells, the M2 muscarinic agonist caused a decrease of cell proliferation without affecting cell survival. Further analysis are addressed to evaluate the capability of these receptors to mediate the differentiative processes in Schwann cell-like, as previously observed in Schwann cells, with particular attention to in vitro myelination.
In conclusion, we hypothesize that a combination of autologous MSC, differentiated in Schwann cell-like, and selective ACh-mimetics may represent a successful strategy to achieve better results in peripheral nerve regeneration.The use of synthetic nerve conduits, in combination with different cell types may represent a promising therapy for the peripheral nerve injuries. The great regenerative capacity of peripheral nervous system (PNS) is due to a permissive environment provided by Schwann cells that proliferate, migrate and release growth factors, either during development or after nerve lesions. Mesenchimal stem cells (MSCs) are an attractive cell source for nerve tissue regeneration. They are able to self-renew and possess multi potent differentiation properties. In particular, adipose MSCs (A-MSCs) appear the most promising source of MSCs. Recent studies have shown that A-MSCs can be differentiated in Schwann-like cells, representing an alternative and reliable source of peripheral glial cells. Acetylcholine (ACh), the main neurotransmitter in central and PNS, has the property to modulate neurite outgrowth and to control Schwann cell proliferation and differentiation. ACh plays important role also in non-neural tissue, but its function in MSC has been poorly investigated. In present work we have characterized the muscarinic cholinergic agonist effects in rat A-MSC and in differentiated Schwann-like derived from A-MSCs. Analysis by RT-PCR, western blot and immunocytochemistry analysis have demonstrated that the A-MSCs express several muscarinic receptor subtypes. MTT analysis and wound healing assay have also demonstrated that the selective activation of M2 receptors caused an inhibition of cell growth and migration of MSCs, indicating the ACh as possible modulator of MSC proliferation and migration. In Schwann cell-like derived from A-MSC, similarly to that observed in Schwann cells, the M2 muscarinic agonist caused a decrease of cell proliferation without affecting cell survival. Further analysis are addressed to evaluate the capability of these receptors to mediate the differentiative processes in Schwann cell-like, as previously observed in Schwann cells, with particular attention to in vitro myelination.
In conclusion, we hypothesize that a combination of autologous MSC, differentiated in Schwann cell-like, and selective ACh-mimetics may represent a successful strategy to achieve better results in peripheral nerve regeneration
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
Muscarinic receptor activation modulates neurotrophic factors production in rat Schwann-like cells derived from adipose mesenchymal stem cells.
No full textMuscarinic receptor activation modulates neurotrophic factors production in rat Schwann-like cells derived from adipose mesenchymal stem cells
Piovesana R1, Faroni A2, Soligo M3, Manni L3, Reid AJ2 & Tata AM1
1Dept. Biol and Biotech. C. Darwin, University of Rome “Sapienza”, Rome, Italy; 2Blond McIndoe Lab, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK; 3Institute of Translational Pharmacology-CNR, Rome, Italy
Peripheral nerve injury is commonly caused by direct mechanical trauma. Regeneration depends on the ability of Schwann cells (SCs) to create a favourable environment, by producing neurotrophic factors. Although SCs are effective in promoting nerve regeneration, they are not a convenient source of transplantable cells to improve outcomes after injury. Mesenchymal Stem Cells derived from adipose tissue (ASCs) seem to be a promising alternative source considering their ability to differentiate towards SC phenotype (Schwann-like).
SCs express different receptors for neurotransmitters. In particular cholinergic stimulation of M2 muscarinic receptor decreases SCs proliferation whilst upregulating myelination. Previously, we demonstrated that Schwann-like cells express muscarinic receptors; in particular the M2 receptor activation resulted in decreased proliferation and reduced migration.
In present work, we have characterised the effects mediated by muscarinic receptors on neurotrophic factors (NFs) expression and production. The selective activation of M2 receptors by arecaidine propargyl ester (APE) caused a significant decrease of the transcript levels for NFs (NGF, BDNF and GDNF), while the non-selective agonist muscarine did not influence NFs mRNA expression. By custom made Elisa Assay, we analysed the production of two different NGF forms, precursor (proNGF) and mature NGF (mNGF). APE treatment induced a decreased release of both NGF forms, whereas muscarine treatment stimulated an increased release of mNGF. Western blot analysis indicated that both agonists caused a significant decrease in the expression of the proNGF isoform at 25 kDa, which is likely involved in the modulation of apoptotic processes.
The data obtained suggest a relevant role of muscarinic receptors in the modulation of NFs production in Schwann-like cells. In particular the ability of both muscarinic agonists to negatively modulate the proNGF isoform, thereby suggesting a neuroprotective role of muscarinic receptors towards regenerating axons
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