Facilitated engraftment of human hematopoietic cells in severe combined immunodeficient mice following a single injection of Cl²MDP liposomes

Transplantation of normal and malignant human hematopoietic cells into severe combined immunodeficient (SCID) mice allows for evaluation of long-term growth abilities of these cells and provides a preclinical model for therapeutic interventions. However, large numbers of cells are required for successful engraftment in preirradiated mice due to residual graft resistance, that may be mediated by cells from the mononuclear phagocytic system. Intravenous (i.v.) injection of liposomes containing dichloromethylene diphosphonate (Cl2MDP) may eliminate mouse macrophages in spleen and liver. In this study outgrowth of acute myeloid leukemia (AML) cells and umbilical cord blood (UCB) cells in SCID mice conditioned with a single i.v. injection of Cl2MDP liposomes in addition to sublethal total body irradiation (TBI) was compared to outgrowth of these cells in SCID mice that had received TBI alone. A two- to 10-fold increase in outgrowth of AML cells was observed in four cases of AML. Administration of 107 UCB cells reproducibly engrafted SCID mice that had been conditioned with Cl2MDP liposomes and TBI, whereas human cells were not detected in mice conditioned with TBI alone. As few as 2 x 104 purified CD34+ UCB cells engrafted in all mice treated with Cl2MDP liposomes. In SCID mice treated with macrophage depletion unexpected graft failures were not observed. Histological examination of the spleen showed that TBI and Cl2MDP liposomes i.v. resulted in a transient elimination of all macrophage subsets in the spleen, whereas TBI had a minor effect. Cl2MDP liposomes were easy to use and their application was not associated with appreciable side-effects. Cl2MDP liposome pretreatment in combination with TBI allows for reproducible outgrowth of high numbers of human hematopoietic cells in SCID mice

An in vitro model for cytogenetic conversion in CML. Interferon-alpha preferentially inhibits the outgrowth of malignant stem cells preserved in long-term culture

IFN-alpha has been shown to prolong survival in chronic myeloid leukemia patients, but its mechanism of action is still not understood. The human cobblestone area-forming cell (CAFC) assay allows for the measurement of the concentration of normal as well as malignant stem cells, while their progeny can be measured in parallel long-term culture (LTC) in flasks

PLM in SME, what are we missing? an alternative view on PLM implementation for SME

Part 10: PLM Maturity, Implementation and AdoptionInternational audienceToday, the concept of Product Lifecycle Management (PLM) is widely accepted as strategically important. It is used to manage the increasing complexity of products, processes and organizations. The need to adopt PLM is growing rapidly for Small to Medium-sized Enterprises (SME). PLM implementations are costly and require a lot of effort. The business impact and financial risks are high for SME. Also, SMEs seem to have relatively more difficulties to benefit from PLM. The study at hand addresses the question, based on literature research, why these difficulties exist and how they can be overcome. To answer that question, three sub questions are discussed in this paper. (1) A generic PLM implementation process structure. (2) A list of identified PLM implementation challenges, specific for SME. (3) A classification of PLM research for SME, related to the common PLM implementation process structure. A hypothesis for a PLM implementation failure mechanism in SMEs is formulated, based on the findings. Also, a potential research gap on operational implementation knowledge in SMEs is identified

Environmental supply chain management in the seafood industry: past, present and future approaches

This review discusses and analyses previous results in identification, development and implementation of cleaner production strategies within the seafood industry. The relevant peer reviewed articles were identified from a structured keyword search and analysed by both supply chain stage (capture and aquaculture, transport, processing, storage and retail), and examination of the cleaner production strategies implemented. Results found entities along the seafood supply chain generally worked separately to improve cleaner production processes and outputs to grow their own businesses. Whilst this approach can be beneficial, it ignores the broader cleaner production potential benefits gained when applied across multiple supply chain entities. The most effective cleaner production strategies for improved environmental performance in each sector of the supply chain were identified with the potential to reduce unnecessary handling, energy usage, storage costs and waste production. To ensure the greatest reduction in environmental impact, a whole of supply chain management system that incorporates life cycle assessment modelling is recommended

Inflammatory Gene Regulatory Networks in Amnion Cells Following Cytokine Stimulation: Translational Systems Approach to Modeling Human Parturition

A majority of the studies examining the molecular regulation of human labor have been conducted using single gene approaches. While the technology to produce multi-dimensional datasets is readily available, the means for facile analysis of such data are limited. The objective of this study was to develop a systems approach to infer regulatory mechanisms governing global gene expression in cytokine-challenged cells in vitro, and to apply these methods to predict gene regulatory networks (GRNs) in intrauterine tissues during term parturition. To this end, microarray analysis was applied to human amnion mesenchymal cells (AMCs) stimulated with interleukin-1β, and differentially expressed transcripts were subjected to hierarchical clustering, temporal expression profiling, and motif enrichment analysis, from which a GRN was constructed. These methods were then applied to fetal membrane specimens collected in the absence or presence of spontaneous term labor. Analysis of cytokine-responsive genes in AMCs revealed a sterile immune response signature, with promoters enriched in response elements for several inflammation-associated transcription factors. In comparison to the fetal membrane dataset, there were 34 genes commonly upregulated, many of which were part of an acute inflammation gene expression signature. Binding motifs for nuclear factor-κB were prominent in the gene interaction and regulatory networks for both datasets; however, we found little evidence to support the utilization of pathogen-associated molecular pattern (PAMP) signaling. The tissue specimens were also enriched for transcripts governed by hypoxia-inducible factor. The approach presented here provides an uncomplicated means to infer global relationships among gene clusters involved in cellular responses to labor-associated signals