Stability of human mesenchymal stem cells during in vitro culture: considerations for cell therapy

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.     

Systemic natural killer activity following cardiac engraftment in the rat: lack of correlation with graft survival

The systemic NK activity was studied both in untreated rats which acutely reject allogeneic heterotopic heart grafts and in cyclosporine-treated rats which tolerate their transplants. The trend and magnitude of changes in NK activity were similar at all time points for the two animal groups. Compared to naive rats, peak NK activity was noted 7-8 days after engraftment in untreated rats and 7-12 days after engraftment in cyclosporine-treated hosts. In both groups, NK activity returned to normal levels by 3 weeks. No evidence could be found for inactivation of NK cells or their precursors in vivo in ungrafted rats undergoing cyclosporine treatment alone. These data are consistent with prior studies and suggest that non-specific cytotoxic activity does not represent a crucial force contributing to acute rejection of vascularized organ grafts.     

The replication of Hyposoter didymator polydnavirus: Cytopathology of the calyx cells in the parasitoid

Summary— In the ichneumonid wasp Hyposoter didymator, a polydnavirus was detected in the female reproductive tract. With the aim of studying the regulation of polydnavirus replication, the location and the structure of the virus-producing cells were determined, and the virus replication process was followed inside the ovaries of young adult females observed in light and electron microscopy. The examination of ovaries of pupa females revealed that virus replication is initiated within the calyx just prior to adult emergence. This study revealed that the calyx appears to be a specialized virogenic tissue which also has, during late pupal life, a secretory function that alters the function of virus production.     

Les gravures rupestres des Pléiades de la montagne sacrée du Bego,Tende, Alpes-Maritimes,France

The stellar cluster of the Pleiads is depicted on two carved rocks in the Merveilles valley, in the mont Bego region, by six main zones, surrounded by several scattered cupmarks. On one of these rocks, referred to as “the Dancer”, the stellar cluster of the Pleiads is depicted above a carved halberd in a westerly direction, suggesting the heliac setting. On the other, the rock referred to as “the Pleiads”, the stellar cluster is depicted in the south, suggesting its zenith. Taking the precession of the equinoxes into account, it is possible to determine the date in the year of the heliac setting of the Pleiads in the west if the millennium is known. The latter is estimated between 3300 and 1800 years BC by comparing the types of arms carved into the rocks with those discovered in archaeological sites. Although today it is difficult to reach the Merveilles valley during the month of March because of snow, it was probably possible between 3000 and 2000 years before our era, at the end of the Atlantic period, during the Chalcolithic climatic optimum, when the climate was slightly warmer than at present.     

Competitive inhibition of specific steroid-protein binding: Practical use of relative competition ratios for the derivation of equilibrium inhibition constants

The relative competition ratio (RCR) is widely used to express the relative affinities of inhibitor(s) and agonist for a binding protein. The RCR is not a constant; it depends on the concentrations of binding sites and of radioactive hormone, and on the presence of nonsaturable binding component(s). According to the assay conditions used, equating the RCR value to the ratio Ka/Ki of the equilibrium association constants of agonist and inhibitor can lead to large errors. In the case of homogeneous non-interacting binding sites, simple correction factors permit one to calculate the ratio Ka/Ki from the measured RCR value. Calculations are given for the eventual contribution of nonsaturable binding components. Corrections can be unnecessary under well defined experimental conditions, where the bound fraction of hormone in absence of competitor is reduced by using a large dilution of binding protein and/or an increased concentration of radioactive hormone.