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No evidence of transdifferentiation of human mesenchymal or hematopoietic stem cells into cardiomyocytes following coculture with neonatal rat cardiomyocytes
No full textBackground: Several clinical trials have shown that stem cell based therapy may improve heart function. Both bone marrow derived mesenchymal (MSC) as well as hematopoietic stem cells (HSC) are reported to be multipotent. This study investigates whether neonatal rat cardiomyocytes (NRCM), when co-cultured, can induce transdifferentiation of either MSC or HSC into cardiomyocytes (CM). Methods and results: Ex vivo expanded human bone marrow derived MSC showed expression of CD49c, CD73, CD90, CD105 but not of CD34, CD45, CD106
and CD184. The expanded MSC kept their multipotent characteristics. In contrast, HSC were
freshly isolated by flow-sorting based on their expression of CD133 CD34 . Co-cultures,
using cell tracker green (5-chloromethylfluorescein diacetate) labelled MSC or HSC and cell
tracker red (5-(and6)-(((4-chloromethyl)benzoyl)amino)tetramethylrhodamin) labelled NRCM,
were performed at different ratios (1:6, 1:4, 1:3 and 1:1). Since several reports indicate that
dimethylsulfoxide (DMSO) and 5-azacytidin (5-aza) induce myocardial differentiation, 1% DMSO
for 48h or 3 M 5-aza for 24h was added to the co-cultures and compared to conditions
without additives. After three weeks green and red labelled cells were separated by
flow-sorting and cardiac gene expression was analyzed by RT-PCR. Co-culturing MSC induced
the expression of troponin T (TnT) and GATA-4. However, no expression of -actinin, myosin
heavy chain (MHC) or troponin I (TnI) could be detected. Furthermore, co-culturing HSC, could
only induce the expression of TnT, but no expression of -actinin, MHC, TnI or GATA-4 was
observed. Transmission electron microscopy confirmed the absence of sarcomeric organization
both in co-cultured MSC and HSC. Conclusions: This in vitro co-culture study obtained no convincing evidence of transdifferentiation of either MSC of HSC into CM. Despite the induction of Tnt and GATA-4, several cardiac specific genes are not expressed after 3 weeks of co-culture. No influence of DMSO or 5-aza on the transdifferentiation of MSC or HSC could be detected. Therefore, the reported functional improvement following cell based therapy for myocardial infarction may be due to other mechanisms than transdifferentiation of MSC or HSC
Suppressed increase in blood endothelial progenitor cell content as result of single exhaustive exercise bout in male revascularised coronary artery disease patients.
No full textSuppressed increase in blood endothelial progenitor cell content as result of single exhaustive exercise bout in male revascularised coronary artery disease patients.
No full textCardiac Regenerative Therapy: from bone marrow stem cells to cardiac progenitors
No full textAfter a MI the heart function is severely diminished due to an irreversible loss of CMs. The heart is no longer considered a static organ but contains some intrinsic regenerative capacity which however is not sufficient to restore function after MI. Regenerative stem cell therapy is a promising approach to improve cardiac function. Since Bone marrow-derived stem cells can be transplanted in a autologous setting and are easy accessible, they were seen as a potential source of stem cells to be transplanted in the infarcted heart. In chapter 3 we described the isolation, characterization, functionality and myocardial differentiation potential of bone marrow-derived MSCs. RT-PCR showed that after 3 weeks of culture in a cardiac micro-environment only the expression of TnT and GATA-4 was induced. The limited cardiac differentiation capacity of these MSCs was shown by immunofluorescence, no cTnT expression at the protein level, and TEM, no sarcomeric organization. In conclusion, these data suggest that MSCs are not able to differentiate in functional CMs...
Cardiac Regenerative Therapy: from bone marrow stem cells to cardiac progenitors
No full textAfter a MI the heart function is severely diminished due to an irreversible loss of CMs. The heart is no longer considered a static organ but contains some intrinsic regenerative capacity which however is not sufficient to restore function after MI. Regenerative stem cell therapy is a promising approach to improve cardiac function. Since Bone marrow-derived stem cells can be transplanted in a autologous setting and are easy accessible, they were seen as a potential source of stem cells to be transplanted in the infarcted heart. In chapter 3 we described the isolation, characterization, functionality and myocardial differentiation potential of bone marrow-derived MSCs. RT-PCR showed that after 3 weeks of culture in a cardiac micro-environment only the expression of TnT and GATA-4 was induced. The limited cardiac differentiation capacity of these MSCs was shown by immunofluorescence, no cTnT expression at the protein level, and TEM, no sarcomeric organization. In conclusion, these data suggest that MSCs are not able to differentiate in functional CMs...
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
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