6 results on '"Düllmann J"'
Search Results
2. Primary human hepatocytes on biodegradable poly(l-lactic acid) matrices: a promising model for improving transplantation efficiency with tissue engineering.
- Author
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Török E, Lutgehetmann M, Bierwolf J, Melbeck S, Düllmann J, Nashan B, Ma PX, and Pollok JM
- Subjects
- Biomarkers metabolism, Bioreactors, Blotting, Northern, Cell Separation, Cell Shape, Cell Survival, Cells, Cultured, Fluorescent Antibody Technique, Hepatocytes metabolism, Hepatocytes ultrastructure, Humans, Immunohistochemistry, Microscopy, Electron, Scanning, Microscopy, Electron, Transmission, Polyesters, Serum Albumin genetics, Serum Albumin metabolism, Time Factors, Urea metabolism, alpha 1-Antitrypsin metabolism, Absorbable Implants, Hepatocytes transplantation, Lactic Acid, Liver Regeneration, Polymers, Tissue Engineering methods, Tissue Scaffolds
- Abstract
Liver transplantation is an established treatment for acute and chronic liver disease. However, because of the shortage of donor organs, it does not fulfill the needs of all patients. Hepatocyte transplantation is promising as an alternative method for the treatment of end-stage liver disease and as bridging therapy until liver transplantation. Our group has been working on the optimization of matrix-based hepatocyte transplantation. In order to increase cell survival after transplantation, freshly isolated human hepatocytes were seeded onto biodegradable poly(l-lactic acid) (PLLA) polymer scaffolds and were cultured in a flow bioreactor. PLLA discs were seeded with human hepatocytes and exposed to a recirculated medium flow for 6 days. Human hepatocytes formed spheroidal aggregates with a liver-like morphology and active metabolic function. Phase contrast microscopy showed increasing numbers of spheroids of increasing diameter during the culture period. Hematoxylin and eosin histology showed viable and intact hepatocytes inside the spheroids. Immunohistochemistry confirmed sustained hepatocyte function and a preserved hepatocyte-specific cytoskeleton. Albumin, alpha-1-antitrypsin, and urea assays showed continued production during the culture period. Northern blot analysis demonstrated increasing albumin signals. Scanning electron micrographs showed hepatocyte spheroids with relatively smooth undulating surfaces and numerous microvilli. Transmission electron micrographs revealed intact hepatocytes and junctional complexes with coated pits and vesicles inside the spheroids. Therefore, we conclude that primary human hepatocytes, precultured in a flow bioreactor on a PLLA scaffold, reorganize to form morphologically intact liver neotissue, and this might offer an optimized method for hepatocyte transplantation because of the expected reduction of the initial cell loss, the high regenerative potential in vivo, and the preformed functional integrity., (Copyright © 2011 American Association for the Study of Liver Diseases.)
- Published
- 2011
- Full Text
- View/download PDF
3. Clonal dominance of hematopoietic stem cells triggered by retroviral gene marking.
- Author
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Kustikova O, Fehse B, Modlich U, Yang M, Düllmann J, Kamino K, von Neuhoff N, Schlegelberger B, Li Z, and Baum C
- Subjects
- Animals, Antigens, CD34 genetics, Bone Marrow Transplantation, DNA-Binding Proteins genetics, Down-Regulation, Humans, Ligase Chain Reaction, MDS1 and EVI1 Complex Locus Protein, Mice, Mice, Inbred C57BL, Polymerase Chain Reaction, Proto-Oncogenes genetics, Transcription Factors genetics, Transcription, Genetic, Transgenes, Up-Regulation, Genetic Vectors, Hematopoiesis, Hematopoietic Stem Cell Transplantation, Hematopoietic Stem Cells physiology, Mutagenesis, Insertional, Retroviridae genetics, Virus Integration
- Abstract
Gene marking with replication-defective retroviral vectors has been used for more than 20 years to track the in vivo fate of cell clones. We demonstrate that retroviral integrations themselves may trigger nonmalignant clonal expansion in murine long-term hematopoiesis. All 29 insertions recovered from clones dominating in serially transplanted recipients affected loci with an established or potential role in the self-renewal or survival of hematopoietic stem cells. Transcriptional dysregulation occurred in all 12 insertion sites analyzed. These findings have major implications for diagnostic gene marking and the discovery of genes regulating stem cell turnover.
- Published
- 2005
- Full Text
- View/download PDF
4. Side effects of retroviral gene transfer into hematopoietic stem cells.
- Author
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Baum C, Düllmann J, Li Z, Fehse B, Meyer J, Williams DA, and von Kalle C
- Subjects
- Animals, Gene Expression, Genetic Vectors, Hematopoiesis, Hematopoietic Stem Cell Transplantation, Humans, Immunity, Risk Factors, Transfection, Gene Transfer Techniques adverse effects, Genetic Therapy adverse effects, Hematopoietic Stem Cells, Retroviridae genetics
- Abstract
Recent conceptual and technical improvements have resulted in clinically meaningful levels of gene transfer into repopulating hematopoietic stem cells. At the same time, evidence is accumulating that gene therapy may induce several kinds of unexpected side effects, based on preclinical and clinical data. To assess the therapeutic potential of genetic interventions in hematopoietic cells, it will be important to derive a classification of side effects, to obtain insights into their underlying mechanisms, and to use rigorous statistical approaches in comparing data. We here review side effects related to target cell manipulation; vector production; transgene insertion and expression; selection procedures for transgenic cells; and immune surveillance. We also address some inherent differences between hematopoiesis in the most commonly used animal model, the laboratory mouse, and in humans. It is our intention to emphasize the need for a critical and hypothesis-driven analysis of "transgene toxicology," in order to improve safety, efficiency, and prognosis for the yet small but expanding group of patients that could benefit from gene therapy.
- Published
- 2003
- Full Text
- View/download PDF
5. Murine leukemia induced by retroviral gene marking.
- Author
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Li Z, Düllmann J, Schiedlmeier B, Schmidt M, von Kalle C, Meyer J, Forster M, Stocking C, Wahlers A, Frank O, Ostertag W, Kühlcke K, Eckert HG, Fehse B, and Baum C
- Subjects
- Animals, Bone Marrow Cells metabolism, Bone Marrow Transplantation, DNA-Binding Proteins genetics, DNA-Binding Proteins metabolism, Genetic Therapy, Hematopoiesis, Extramedullary, MDS1 and EVI1 Complex Locus Protein, Mice, Mice, Inbred C57BL, Receptor, Nerve Growth Factor, Receptor, trkA genetics, Receptor, trkA metabolism, Receptors, Nerve Growth Factor metabolism, Transcription Factors genetics, Transgenes, Gene Transfer, Horizontal, Genetic Vectors, Leukemia, Monocytic, Acute etiology, Preleukemia etiology, Proto-Oncogenes, Receptors, Nerve Growth Factor genetics, Retroviridae genetics
- Published
- 2002
- Full Text
- View/download PDF
6. Lectin histochemistry of the spleen: a new lectin visualizes the stromal architecture of white pulp and the sinuses of red pulp.
- Author
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Düllmann J, Feldhaus S, Van Damme EJ, Peumans WJ, and Schumacher U
- Subjects
- Animals, Carbohydrates chemistry, Female, Histocytochemistry, Iron, Lymphocytes metabolism, Macrophages metabolism, Male, Rats, Rats, Wistar, Spleen chemistry, Spleen cytology, Spleen metabolism, Staining and Labeling, Lectins, Spleen ultrastructure
- Abstract
The subcompartmentalization of the white pulp in the spleen is the result of interactions of specific resident stromal cells and migrating subtypes of lymphocytes. Because carbohydrate residues of cell membranes and extracellular matrices are involved in cell-cell and cell-matrix interactions, they were investigated in rat spleen by a broad panel of lectins. Splenic macrophages, which were also demonstrated by Perls' Prussian blue reaction, were labeled selectively by most mannose-specific lectins and gave the characteristic distribution patterns in all splenic (sub)compartments. One recently isolated lectin, Chelidonium majus agglutinin (CMA), visualized predominantly central arterioles, the reticular meshwork (RM) in the periarteriolar lymphatic sheaths (PALS), the circumferential reticulum cells limiting PALS and follicles, and some follicular dendritic cells (FDCs) in white pulp. The endothelial cells of venous sinuses in red pulp were also labeled by CMA and, if frozen sections were used, CMA also labeled the macrophages of the red pulp. Compared to CMA, the monoclonal antibody CD11, which can be used only in frozen sections, stained almost solely the fibrous (extracellular) component of the RM. Because CMA stains the reticulum cells in particular, it is better suited to visualize the stromal architecture of splenic white pulp than the monoclonal antibody. Because CMA can be applied to paraffin-embedded material, it is a particularly useful tool to study the splenic stromal architecture in archival material.
- Published
- 2000
- Full Text
- View/download PDF
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