Mesenchymal stem cells support expansion of in vitro irradiated CD34(+) cells in the presence of SCF, FLT3 ligand, TPO and IL3: potential application to autologous cell therapy in accidentally irradiated victims

Ex vivo expansion of residual autologous hematopoietic stem and progenitor cells collected from victims soon after accidental irradiation (autologous cell therapy) may represent an additional or alternative approach to cytokine therapy or allogeneic transplantation. Peripheral blood CD34+ cells could be a useful source of cells for this process provided that collection and ex vivo expansion of hematopoietic stem and progenitor cells could be optimized. Here we investigated whether mesenchymal stem cells could sustain culture of irradiated peripheral blood CD34+ cells. In vitro irradiated (4 Gy 60Co gamma rays) or nonirradiated mobilized peripheral blood CD34+ cells from baboons were cultured for 7 days in a serum-free medium supplemented with stem cell factor+thrombopoietin+interleukin 3+FLT3 ligand (50 ng/ml each) in the presence or absence of mesenchymal stem cells. In contrast to cultures without mesenchymal stem cells, irradiated CD34+ cells cultured with mesenchymal stem cells displayed cell amplification, i.e. CD34+ (4.9-fold), CD34++ (3.8-fold), CD34++/Thy-1+ (8.1-fold), CD41+ (12.4-fold) and MPO+ (50.6-fold), although at lower levels than in nonirradiated CD34+ cells. Fourteen times more clonogenic cells, especially BFU-E, were preserved when irradiated cells were cultured on mesenchymal stem cells. Moreover, we showed that the effect of mesenchymal stem cells is related mainly to the reduction of apoptosis and involves cell-cell contact rather than production of soluble factor(s). This experimental model suggests that mesenchymal stem cells could provide a crucial tool for autologous cell therapy applied to accidentally irradiated victims.     

Science and society: promoting the learning of immunology in developing countries

In 2005, the economic gap between developing and developed countries is bigger than ever, and this has consequences for public health. So, to sustain education and research in the most resource-constrained regions, it is necessary to promote local teaching of the immunology of infectious diseases. This Perspective article reviews the use and expected efficiency of current Internet-based tools for higher education in the biomedical sciences in developing countries. We also discuss other approaches to improve access to updated training in immunology for students in the poorest countries.     

Stromal cell-derived factor-1 (SDF-1)\CXCR4 couple plays multiple roles on haematopoietic progenitors at the border between the old cytokine and new chemokine worlds: survival, cell cycling and trafficking

Generation of haematopoietic cells is regulated by cellular and humoral interactions in which stromal cells, adhesion molecules, cytokines and chemokines play a crucial role. Among the chemokines, SDF-1 and its CXCR4 receptor have been reported to be key players in the nesting of haematopoietic progenitors within the bone marrow. Disruption of the SDF-1\CXCR4 axis results in cell mobilization and may participate in leukaemia extramedullary infiltration. In this review we will discuss the manifold roles of the SDF-1 chemokine and of its receptor in haematopoiesis regulation. By recruiting quiescent progenitors, by participating in their survival\cycling and by sensitizing them to further cytokine synergistic action, SDF-1 likely contributes to haematopoiesis homeostasis under physiological conditions and in stress situations. The complexity of the SDF-1\CXCR4 interactions in the regulation of haematopoiesis illustrates a dynamic and sequential cross-talk between chemokine and cytokine\growth factor worlds. Because of their pleiotropic effects on haematopoietic progenitor trafficking, survival and proliferation, the SDF-1\CXCR4 couple could be considered as promising molecules for improvement of cell-based therapy protocols in haematopoietic transplantation.     

Evidence for early infection of nonneoplastic natural killer cells by Epstein-Barr virus

We examined lymph nodes and tonsils from patients with infectious mononucleosis by combined detection of EBV-encoded RNA and a specific marker of natural killer (NK) cells, PEN5. A small number of Epstein-Barr virus (EBV) latently infected nonneoplastic NK cells were detected. Our data demonstrate that NK cells are natural targets of EBV and that infection of these cells is an early event observed during primary EBV infection.     

Effect of prostaglandin 16,16 dimethyl E2 methyl ester on the pregnant human uterus

The oxytocic properties of prostaglandin 16,16 dimethyl E₂ methyl ester were investigated during the second trimester of pregnancy. As an abortifacient, this compound compared unfavorably to the 15 methyl analogs of prostaglandin E₂, with a lower rate of effectiveness and a relatively high incidence of side effects.     

Pax3( GFP ) , a new reporter for the melanocyte lineage, highlights novel aspects of PAX3 expression in the skin

The paired box gene 3 (Pax3) is expressed during pigment cell development. We tested whether the targeted allele Pax3(GFP) can be used as a reporter gene for pigment cells in the mouse. We found that enhanced green fluorescent protein (GFP) can be seen readily in every melanoblast and melanocyte in the epidermis and hair follicles of Pax3(GFP/+) heterozygotes. The GFP was detected at all differentiation stages, including melanocyte stem cells. In the dermis, Schwann cells and nestin-positive cells of the piloneural collars resembling the nestin-positive hair follicle multipotent stem cells exhibited a weaker GFP signal. Pigment cells could be purified by fluorescent activated cell sorting and grown in vitro without feeder cells, giving pure cultures of melanocytes. The Schwann cells and nestin-positive cells of the piloneural collars were FACS-isolated based on their weak expression of GFP. Thus Pax3(GFP) can discriminate distinct populations of cells in the skin.