18 results match your criteria: "University of Bonn Medical Faculty and University Hospital Bonn[Affiliation]"
Stem Cell Res Ther
December 2024
Institute of Reconstructive Neurobiology, University of Bonn Medical Faculty and University Hospital Bonn, Venusberg-Campus 1, Bonn, 53127, Germany.
Transplantation of induced pluripotent stem cell-derived neural cells represents a promising strategy for treating neurodegenerative diseases. However, reprogramming of somatic cells and their subsequent neural differentiation is complex and time-consuming, thereby impeding autologous applications. Recently, direct transcription factor-based conversion of blood cells into induced neural stem cells (iNSCs) has emerged as a potential alternative.
View Article and Find Full Text PDFInt J Mol Sci
March 2024
Institute of Reconstructive Neurobiology, University of Bonn Medical Faculty and University Hospital Bonn, 53127 Bonn, Germany.
Induced pluripotent stem cells (iPSCs) and their derivatives have been described to display epigenetic memory of their founder cells, as well as de novo reprogramming-associated alterations. In order to selectively explore changes due to the reprogramming process and not to heterologous somatic memory, we devised a circular reprogramming approach where somatic stem cells are used to generate iPSCs, which are subsequently re-differentiated into their original fate. As somatic founder cells, we employed human embryonic stem cell-derived neural stem cells (NSCs) and compared them to iPSC-derived NSCs derived thereof.
View Article and Find Full Text PDFNeuro Oncol
December 2023
Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Background: Glioblastomas are characterized by aggressive and infiltrative growth, and by striking heterogeneity. The aim of this study was to investigate whether tumor cell proliferation and invasion are interrelated, or rather distinct features of different cell populations.
Methods: Tumor cell invasion and proliferation were longitudinally determined in real-time using 3D in vivo 2-photon laser scanning microscopy over weeks.
J Perinat Med
July 2023
Institute of Reconstructive Neurobiology, University of Bonn Medical Faculty and University Hospital Bonn, Bonn, Germany.
Recreating human cell and organ systems has tremendous potential for disease modeling, drug discovery and regenerative medicine. The aim of this short overview is to recapitulate the impressive progress that has been made in the fast-developing field of cell programming during the past years, to illuminate the advantages and limitations of the various cell programming technologies for addressing nervous system disorders and to gauge their impact for perinatal medicine.
View Article and Find Full Text PDFPain
August 2023
Translational Pain Research, Department of Anaesthesiology and Intensive Care Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Induced pluripotent stem cells (iPSCs) have enabled the generation of various difficult-to-access cell types such as human nociceptors. A key challenge associated with human iPSC-derived nociceptors (hiPSCdNs) is their prolonged functional maturation. While numerous studies have addressed the expression of classic neuronal markers and ion channels in hiPSCdNs, the temporal development of key signaling cascades regulating nociceptor activity has remained largely unexplored.
View Article and Find Full Text PDFMammalian SWI/SNF/BAF chromatin remodeling complexes influence cell lineage determination. While the contribution of these complexes to neural progenitor cell (NPC) proliferation and differentiation has been reported, little is known about the transcriptional profiles that determine neurogenesis or gliogenesis. Here, we report that BCL7A is a modulator of the SWI/SNF/BAF complex that stimulates the genome-wide occupancy of the ATPase subunit BRG1.
View Article and Find Full Text PDFStem Cell Rev Rep
February 2023
LIFE & BRAIN GmbH, Venusberg-Campus 1, 53127, Bonn, Germany.
Development
October 2022
Institute of Physical and Theoretical Chemistry, University of Bonn, Wegelerstr. 12, 53115 Bonn, Germany.
Organoids are stem cell-derived three-dimensional cultures offering a new avenue to model human development and disease. Brain organoids allow the study of various aspects of human brain development in the finest details in vitro in a tissue-like context. However, spatial relationships of subcellular structures, such as synaptic contacts between distant neurons, are hardly accessible by conventional light microscopy.
View Article and Find Full Text PDFCommun Biol
June 2022
Institute of Molecular Medicine, University Medical Center Mainz, Mainz, Germany.
Charcot-Marie-Tooth (CMT) disease 4A is an autosomal-recessive polyneuropathy caused by mutations of ganglioside-induced differentiation-associated protein 1 (GDAP1), a putative glutathione transferase, which affects mitochondrial shape and alters cellular Ca homeostasis. Here, we identify the underlying mechanism. We found that patient-derived motoneurons and GDAP1 knockdown SH-SY5Y cells display two phenotypes: more tubular mitochondria and a metabolism characterized by glutamine dependence and fewer cytosolic lipid droplets.
View Article and Find Full Text PDFSci Rep
May 2022
Institute of Reconstructive Neurobiology, University of Bonn Medical Faculty and University Hospital Bonn, Venusberg-Campus 1, Building 76, 53127, Bonn, Germany.
Human brain cells generated by in vitro cell programming provide exciting prospects for disease modeling, drug discovery and cell therapy. These applications frequently require efficient and clinically compliant tools for genetic modification of the cells. Recombinant adeno-associated viruses (AAVs) fulfill these prerequisites for a number of reasons, including the availability of a myriad of AAV capsid variants with distinct cell type specificity (also called tropism).
View Article and Find Full Text PDFCell Rep Methods
May 2021
German Center for Neurodegenerative Diseases (DZNE), Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Venusberg-Campus 1, Gebäude 99, Bonn, North Rhine-Westphalia 53127, Germany.
Mitochondria sustain the energy demand of the cell. The composition and functional state of the mitochondrial oxidative phosphorylation system are informative indicators of organelle bioenergetic capacity. Here, we describe a highly sensitive and reproducible method for a single-cell quantification of mitochondrial CI- and CIV-containing respiratory supercomplexes (CI∗CIV-SCs) as an alternative means of assessing mitochondrial respiratory chain integrity.
View Article and Find Full Text PDFNat Neurosci
February 2022
Department of Immunology, Harvard Medical School, Boston, MA, USA.
Bacterial products can act on neurons to alter signaling and function. In the present study, we found that dorsal root ganglion (DRG) sensory neurons are enriched for ANTXR2, the high-affinity receptor for anthrax toxins. Anthrax toxins are composed of protective antigen (PA), which binds to ANTXR2, and the protein cargoes edema factor (EF) and lethal factor (LF).
View Article and Find Full Text PDFStem Cell Res
April 2021
Janssen Research & Development, Neuroscience Therapeutic Area (Johnson & Johnson), Turnhoutseweg 30, 2340 Beerse, Belgium. Electronic address:
APOE genotype is the strongest genetic risk factor for Alzheimer's Disease (AD). The low degree of homology between mouse and human APOE is a concerning issue in preclinical models currently used to study the role of this gene in AD pathophysiology. A key objective of ADAPTED (Alzheimer's Disease Apolipoprotein Pathology for Treatment Elucidation and Development) project was to generate in vitro models that better recapitulate human APOE biology.
View Article and Find Full Text PDFGlia
June 2021
Institute of Reconstructive Neurobiology, University of Bonn Medical Faculty and University Hospital Bonn, Bonn, Germany.
Genome-wide association studies demonstrated that polymorphisms in the CD33/sialic acid-binding immunoglobulin-like lectin 3 gene are associated with late-onset Alzheimer's disease (AD). CD33 is expressed on myeloid immune cells and mediates inhibitory signaling through protein tyrosine phosphatases, but the exact function of CD33 in microglia is still unknown. Here, we analyzed CD33 knockout human THP1 macrophages and human induced pluripotent stem cell-derived microglia for immunoreceptor tyrosine-based activation motif pathway activation, cytokine transcription, phagocytosis, and phagocytosis-associated oxidative burst.
View Article and Find Full Text PDFFront Bioeng Biotechnol
November 2020
Institute of Reconstructive Neurobiology, University of Bonn Medical Faculty and University Hospital Bonn, Bonn, Germany.
While human induced pluripotent stem cells (hiPSCs) provide novel prospects for disease-modeling, the high phenotypic variability seen across different lines demands usage of large hiPSC cohorts to decipher the impact of individual genetic variants. Thus, a much higher grade of parallelization, and throughput in the production of hiPSCs is needed, which can only be achieved by implementing automated solutions for cell reprogramming, and hiPSC expansion. Here, we describe the StemCellFactory, an automated, modular platform covering the entire process of hiPSC production, ranging from adult human fibroblast expansion, Sendai virus-based reprogramming to automated isolation, and parallel expansion of hiPSC clones.
View Article and Find Full Text PDFEur J Cancer
November 2020
Institute of Reconstructive Neurobiology, Division of Stem Cell Pathologies, Life and Brain Centre, University of Bonn Medical Faculty and University Hospital Bonn, Germany; DKFZ Division Translational Neurooncology at the West German Cancer Center (WTZ), DKTK Partner Site, University Hospital Essen, Germany; German Cancer Consortium (DKTK), Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany.
Background: The protease inhibitor ritonavir (RTV) is a clinical-stage inhibitor of the human immunodeficiency virus. In a drug repositioning approach, we here exhibit the additional potential of RTV to augment current treatment of glioblastoma, the most aggressive primary brain tumour of adulthood.
Methods: We explored the antitumour activity of RTV and mechanisms of action in a broad spectrum of short-term expanded clinical cell samples from primary and recurrent glioblastoma and in a cohort of conventional cell lines and non-tumour human neural controls in vitro.
Front Cell Neurosci
May 2020
Institute of Reconstructive Neurobiology, Life & Brain Center, University of Bonn Medical Faculty and University Hospital Bonn, Bonn, Germany.
Traditionally, generation of donor cells for brain repair has been dominated by the application of extrinsic growth factors and morphogens. Recent advances in cell engineering strategies such as reprogramming of somatic cells into induced pluripotent stem cells and direct cell fate conversion have impressively demonstrated the feasibility to manipulate cell identities by the overexpression of cell fate-determining transcription factors. These strategies are now increasingly implemented for transcription factor-guided differentiation of neural precursors and forward programming of pluripotent stem cells toward specific neural subtypes.
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