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Transcriptonal profile of cord lining epithelial cells after phage integrase mediated integration

ABSTRACT: The two obstacles that impede a wider application of genetically modified cells expressing therapeutic transgenes for ex vivo gene therapy are the immune mediated rejection of the transplanted cells, combined with their potential to cause iatrogenic oncogenesis. In this study we describe a new cellular vehicle for this form of therapy, termed the cord lining epithelial cell (CLEC). CLECs are derived from the human amnion and incorporate many of the immunoregulatory functions associated with the fetal/maternal interface. We show that CLECs can be safely transfected by phage φC31 integrase to accomplish site-specific integration of a therapeutic human transgene. We also show that transplanted CLECs are not oncogenic in vivo and can be maintained in immunocompetent mice where acute xeno-rejection rapidly destroys other human cell types. Finally, we demonstrate the utility of CLECs for ex vivo gene therapy by delivering human coagulation factor 8 to mice with Hemophilia A.

ORGANISM(S): Homo sapiens

PROVIDER: GSE12510 | GEO | 2008/08/23

SECONDARY ACCESSION(S): PRJNA113261

REPOSITORIES: GEO

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Transcription profiling of human cord lining epithelial cells after phage integrase mediated integration

Project description:The two obstacles that impede a wider application of genetically modified cells expressing therapeutic transgenes for ex vivo gene therapy are the immune mediated rejection of the transplanted cells, combined with their potential to cause iatrogenic oncogenesis. In this study we describe a new cellular vehicle for this form of therapy,; termed the cord lining epithelial cell (CLEC). CLECs are derived from the human amnion and incorporate many of the immunoregulatory functions associated with the fetal/maternal interface. We show that CLECs can be safely transfected by phage ÏC31 integrase to accomplish site-specific integration of a therapeutic human transgene. We also show that transplanted CLECs are not oncogenic in vivo and can be maintained in immunocompetent mice where acute xeno-rejection rapidly destroys other human cell types. Finally, we demonstrate the utility of CLECs for ex vivo gene therapy by delivering human coagulation factor 8 to mice with Hemophilia A. Experiment Overall Design: The transcriptome datasets of human umbilical cord lining epithelial cells were compared before(CLEC) and 1 month after(CLEC-GFP) phage integrase mediated integration of EGFP cDNA into the genome. Transcriptome datasets were generated in singles and genes differentiallty expressed in cells before and after phage integrase treatment were analysed. Genes differentially expressed by at least 2 fold as compared to untreated CLEC were considered to be significantly dysregulated. List of genes with significant dysregulation were used for further analysis and to used to determine if genomic integration events had resulted in any potential geno-toxicity.

2008-10-25 | E-GEOD-12510 | biostudies-arrayexpress

Analysis of copy number change in cord lining epithelial cells after phage integrase mediated genomic integration.

2008-09-01 | GSE12629 | GEO

Analysis of copy number change in cord lining epithelial cells after phage integrase mediated genomic integration.

Project description:The two obstacles that impede a wider application of genetically modified cells expressing therapeutic transgenes for ex vivo gene therapy are the immune mediated rejection of the transplanted cells, combined with their potential to cause iatrogenic oncogenesis. In this study we describe a new cellular vehicle for this form of therapy, termed the cord lining epithelial cell (CLEC). CLECs are derived from the human amnion and incorporate many of the immunoregulatory functions associated with the fetal/maternal interface. We show that CLECs can be safely transfected by phage φC31 integrase to accomplish site-specific integration of a therapeutic human transgene. We also show that transplanted CLECs are not oncogenic in vivo and can be maintained in immunocompetent mice where acute xeno-rejection rapidly destroys other human cell types. Finally, we demonstrate the utility of CLECs for ex vivo gene therapy by delivering human coagulation factor 8 to mice with Hemophilia A. High-resolution copy number profiling was performed on genomic DNA of untreated (GSM315546 and GSM315713) and phage integrase modified CLECs (GSM315974 and GSM316895) using the Human Mapping 500K Array Set (Affymetrix) and the data analyzed using GeneChip Chromosome Copy Number Analysis Tool. Regions of copy number gain or loss were defined as having 3 consecutive SNPs concordant for significant copy number abnormalities. Log2 signal intensity ratios >0.3 and <-0.3 were criteria for significant copy number gain and loss, respectively.

2008-09-01 | E-GEOD-12629 | biostudies-arrayexpress

WNT2B is required for development and function of human intestine

Project description:The experiment goal was to identify differentially expressed proteins associated with WNT2B mutation p.R69* in human intestinal epithelia. Skin fibroblasts from a patient with the mutation were used to establish human intestinal organoids (HIOs). The hESC H1 cell line was used to generate wild-type WNT2B HIOs for comparison. The HIOs were transplanted into mice to promote maturation for 8 weeks, followed by dissection and crypt isolation to seed ex vivo epithelial (enteroid) cultures. The enteroid cultures were harvested for analysis by tandem mass tag spectrometry.

2023-06-16 | MSV000092189 | MassIVE

Nuclear Receptor NR2F6 as an Alternative Cancer Immune Checkpoint in the T Cell Compartment

Project description:Analyzing mouse tumor models in vivo, human T cells ex vivo and human lung cancer samples, we provide direct evidence that NR2F6 acts as novel immune checkpoint. Genetic ablation of Nr2f6, particularly in combination with blockade of the established PD-L1 cancer immune checkpoint, efficiently delayed tumor progression and improved survival in experimental mouse models. The target genes deregulated in intratumoral T lymphocytes upon genetic ablation of Nr2f6 alone or together with PD-L1 blockade, revealed multiple advantageous transcriptional alterations for effective tumor rejection. In keeping with the above observation, acute Nr2f6 silencing in both mouse and human T cells induced hyper-responsiveness that established a non-redundant T cell-inhibitory function of NR2F6. Analyzing mouse tumor models in vivo, human T cells ex vivo and human lung cancer samples,

2018-03-14 | GSE111796 | GEO

Transcriptome of clec-4 for the nematode Caenorhabditis elegans

Project description:C-type lectin-like domain (CTLD) encoding genes are highly diverse in C. elegans, comprising a clec gene family of 283 members. Since vertebrate CTLD proteins have characterized functions in defense responses against pathogens and since expression of C. elegans clec genes is pathogen-dependent, it is generally assumed that clec genes function in C. elegans immune defenses. In this study we challenged this assumption and focused on the C. elegans clec gene clec-4, whose expression is highly upregulated upon infection with various pathogens. We tested the involvement of clec-4 in the defense response to infection with Pseudomonas aeruginosa PA14, Bacillus thuringiensis BT18247, and the natural pathogen Serratia rubidaea MYb237. Contrary to our expectation clec-4(ok2050) mutant worms were not more susceptible to pathogen infection than wildtype worms. To explore potential redundant function between different C. elegans clec genes, we investigated expression of several clec-4 paralogs, finding that clec-4, clec-41, and clec-42 expression shows similar infection-dependent changes and co-localizes to the intestine. We found that only clec-42 is required for the C. elegans defense response to BT18247 infection and that clec-4 genetically interacts with clec-41 and clec-42. The exact role of clec-4 in pathogen defense responses however remains enigmatic. Our results further indicate that a complex interplay between different clec genes regulates C. elegans defense responses.

2019-12-31 | GSE110913 | GEO

GNPS Drug metabolism by the human gut microbiome

Project description:Ex vivo communities derived from human microbiome samples incubated with a range of drugs.

2019-12-02 | MSV000084641 | GNPS

CD7 promotes extramedullary involvement of the B-cell acute lymphoblastic leukemia line Tanoue by enhancing integrin beta2-dependent cell adhesiveness

Project description:The Tanoue expressing firefly-luciferase gene, Luc-Tanoue, was transplanted into non-obese diabetic/severe combined immunodeficient mice, and cells infiltrated in the brain were cultured ex vivo. This process was repeated 4 times to obtain the highly invasive line Luc-Tanoue-F4. Comparison of the global gene expression signatures of Luc-Tanoue-F4 and Luc-Tanoue indicated that the CD7 gene showed the largest increase in expression among EMI-related genes in Luc-Tanoue-F4. Tanoue expressing firefly-luciferase gene, Luc-Tanoue, was transplanted into non-obese diabetic/severe combined immunodeficient mice, and cells infiltrated in the brain were cultured ex vivo. This process was repeated 4 times to obtain the highly invasive line Luc-Tanoue-F4.

2013-12-27 | E-GEOD-53651 | biostudies-arrayexpress

Feasibility and Safety of MiWEndo-assisted Colonoscopy

Project description:The study involves the planned use of a new microwave-based device during colonoscopy procedures in a small group of patients to assess the preliminary safety of its use and lack of normal clinical practice modification. The device is a final design version, which has been previously tested in several preclinical studies, including: phantom studies, an ex vivo study with human tissues, and an in vivo study with animal model (pig).

| 2743276 | ecrin-mdr-crc

Non-radiated and Radiated lymphocytes from breast cancer patients treated with high-dose hyperfractioned radiotherapy

Project description:The aim of this study was to assess the relationship between gene expression profiles of ex vivo 2 Gy radiated lymphocytes and the development of acute and late toxicity due to hyperfractionated dose-escalation radiation therapy schedule in patientes with advanced breast cancer. The gene expression profiles of ex vivo non-radiated lymphocytes were also examined. Keywords: Toxicity grade analysis. Twelve patients were analyzed. No replicates of each patient was assesed. Human RNA universal control (Stratagene) was used as reference.

2010-05-18 | E-GEOD-15341 | biostudies-arrayexpress

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