Ex vivo expansion and manipulation of human mesenchymal stem cells are important approaches to immunoregulatory and regenerative cell therapies. Although these cells show great potential for use, issues relating to their overall nature emerge as problems in the field. The need for extensive cell quantity amplification in vitro to obtain sufficient cell numbers for use, poses a risk of accumulating genetic and epigenetic abnormalities that could lead to sporadic malignant cell transformation. In this study, we have examined human mesenchymal stem cells derived from bone marrow, over extended culture time, using cytogenetic analyses, mixed lymphocyte reactions, proteomics and gene expression assays to determine whether the cultures would retain their potential for use in subsequent passages. Results indicate that in vitro cultures of these cells demonstrated chromosome variability after passage 4, but their immunomodulatory functions and differentiation capacity were maintained. At the molecular level, changes were observed from passage 5 on, indicating initiation of differentiation. Together, these results lead to the hypothesis that human mesenchymal stem cells cultures can be used successfully in cell therapy up to passage 4. However, use of cells from higher passages would have to be analysed case by case.
We studied the methylation status of the p15(INK4B) and p16(INK4A) genes in 47 pediatric patients with primary MDS, its correlation with subtype, and the role of p15(INK4B) and p16(INK4A) in the evolution of MDS toward AML. Aberrant methylation of the p15(INK4B) gene was detected in 15 of 47 patients (32%), whereas only four patients demonstrated methylation of the p16(INK4A) gene (8%). The frequency of p15(INK4B) methylation was significantly higher in RAEB and RAEB-t subtypes (p<0.003). Aberrant methylation of the p16(INK4A) gene was also more frequent in the subtypes that characterize advanced stages of the disease (p<0.05). Evolution of disease was verified in 17 (36%) of the 47 patients. The association of p15(INK4B) and p16(INK4A) methylation status with evolution of disease was clearly significant (p<0.008 and p<0.05, respectively). These results suggest that methylation of the p15(INK4B) and p16(INK4A) genes is an epigenetic biomarker of pediatric disease evolution.
This study demonstrated that measured outcomes of OBC in a population-based multi-centre setting can be comparable to the outcomes of large volume single centre series.
Of 14 common dolphins, 12 showed non-specific reactive hepatitis and three chronic parasitic cholangitis with lymphoid proliferation. Non-specific reactive hepatitis was shown immunohistochemically to be associated with small clusters of CD3(+) cells in portal areas and hepatic sinusoids. Polyclonal antibody against S100 protein reacted with a variable number of lymphocytes from portal areas and hepatic sinusoids, as well as with Kupffer cells and epithelial cells of the bile ducts. The majority of plasma cells observed in portal areas and hepatic sinusoids were IgG(+). In lymphonodular lesions of chronic parasitic cholangitis, the distribution of immunoreactive cells was similar to that found in the cortex of lymph nodes. The presence of stellate cells similar to follicular dendritic and interdigitating cells expressing S-100 protein and MHC class II antigen in lymphonodular lesions suggested that these were highly organized structures developed to enhance antigen presentation to B and T cells.
Insulin-like growth factor I (IGF-I) is shown to be involved in the regulation of pituitary hormones. High IGF-I concentrations were detected in hypothalamus and pituitary during adulthood. This study was undertaken to analyze the cellular distribution of IGF-I in the hypothalamo-hypophyseal system of the adult rat using immunocytochemical procedures. IGF-I was found to be widely distributed throughout the hypothalamus; it was present in the magnocellular neurons of the supraoptic, paraventricular, and accessory nuclei. Moreover, nerve fibres and puncta containing immunoreactive IGF-I were localized in the median eminence and the posterior lobe of the pituitary. These results support possible IGF-I neuromodulatory or neurohormonal action in the hypothalamus on pituitary hormone regulation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.