المؤلفون: Daniel Sommermeyer, Chloé Beuraud, Monika Braun, Michael Epstein, Philip Hublitz, Michael Esquerré, Audrey Holtzinger, Nadja Wagner, Riga Tawo, Florie Bertrand, Olivia Cypris, Pauline Barron, Stefanie Pfänder, Stephanie Sontag

المصدر: Journal for ImmunoTherapy of Cancer, Vol 11, Iss Suppl 1 (2023)

مصطلحات موضوعية: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2051-1426Test

الوصول الحر: https://doaj.org/article/1b6c6dd10de94ead9a4f07c09f966c27Test

المؤلفون: Michael Trevino, Sergio Perez, Stephanie Sontag, Alex Olmos, Sunggun Jeon, Lyric Richardson

المصدر: Journal of Functional Morphology and Kinesiology, Vol 8, Iss 2, p 53 (2023)

مصطلحات موضوعية: females, log transform, males, mechanomyography, muscle thickness, pennation angle, Diseases of the musculoskeletal system, RC925-935

الوصف: This study examined potential sex-related differences and correlations among the pennation angle (PA), muscle thickness (MT), and mechanomyographic amplitude (MMGRMS)–torque relationships of the vastus lateralis (VL) in 11 healthy males and 12 healthy females. The PA and MT of the VL were quantified with ultrasound. Participants performed an isometric muscle action of the knee extensors that linearly increased to 70% of maximal strength followed by a 12 s plateau. MMG was recorded from the VL. Linear regression models were fit to the log-transformed MMGRMS–torque relationships to calculate b terms (slopes) for the linearly increasing segment. MMGRMS was averaged during the plateau. Males exhibited greater PA (p < 0.001), MT (p = 0.027), b terms (p = 0.005), and MMGRMS (p = 0.016). The b terms were strongly (p < 0.001, r = 0.772) and moderately correlated (p = 0.004, r = 0.571) with PA and MT, respectively, while MMGRMS was moderately correlated with PA (p = 0.018, r = 0.500) and MT (p = 0.014, r = 0.515). The greater mechanical behavior of individuals possessing a larger PA and MT of the VL may reflect increased cross-bridge activity within the muscle fibers. Additionally, PA may help explain sex-related differences in MMGRMS between sexes.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2411-5142/8/2/53Test; https://doaj.org/toc/2411-5142Test

الوصول الحر: https://doaj.org/article/72c1a3f3f0c1464794364ea21935167fTest

المؤلفون: Janik Boehnke, Salim Atakhanov, Marcelo A.S. Toledo, Herdit M. Schüler, Stephanie Sontag, Nicolas Chatain, Steffen Koschmieder, Tim H. Brümmendorf, Rafael Kramann, Martin Zenke

المصدر: Stem Cell Research, Vol 55, Iss , Pp 102490- (2021)

مصطلحات موضوعية: Induced pluripotent stem cell, iPS cells, Hematopoiesis, CXCL4, PF4, JAK2 V617F, Biology (General), QH301-705.5

الوصف: The chemokine CXCL4/platelet factor 4 (PF4) gene, a key player in myelofibrosis, was knocked out by CRISPR/Cas9 in induced pluripotent stem cells (iPS cells) of a polycythemia vera (PV) patient with JAK2 V617F mutation. Two CXCL4KO iPS cell lines with and without JAK2 V617F mutation (UKAi002-B-1 and UKAi002-A-1, respectively) were generated. CXCL4KO iPS cells showed deletion of exon 1 and complete loss of CXCL4 protein. Pluripotency of iPS cells was confirmed by expression of pluripotency markers and trilineage differentiation. CXCL4KO iPS cells are expected to provide a valuable tool for investigating the role of CXCL4 in human diseases.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S1873506121003378Test; https://doaj.org/toc/1873-5061Test

الوصول الحر: https://doaj.org/article/d5201e98c76548fb80312315e5bbd47dTest

المؤلفون: Taiki Satoh, Marcelo A. S. Toledo, Janik Boehnke, Kathrin Olschok, Niclas Flosdorf, Katrin Götz, Caroline Küstermann, Stephanie Sontag, Kristin Seré, Steffen Koschmieder, Tim H. Brümmendorf, Nicolas Chatain, Yoh-ichi Tagawa, Martin Zenke

المصدر: Frontiers in Cell and Developmental Biology, Vol 9 (2021)

مصطلحات موضوعية: induced pluripotent stem cell, iPS cells, hematopoiesis, dendritic cells, DC3, JAK2, Biology (General), QH301-705.5

الوصف: Dendritic cells (DC) are professional antigen-presenting cells that develop from hematopoietic stem cells. Different DC subsets exist based on ontogeny, location and function, including the recently identified proinflammatory DC3 subset. DC3 have the prominent activity to polarize CD8+ T cells into CD8+ CD103+ tissue resident T cells. Here we describe human DC3 differentiated from induced pluripotent stem cells (iPS cells). iPS cell-derived DC3 have the gene expression and surface marker make-up of blood DC3 and polarize CD8+ T cells into CD8+ CD103+ tissue-resident memory T cells in vitro. To test the impact of malignant JAK2 V617F mutation on DC3, we differentiated patient-specific iPS cells with JAK2 V617Fhet and JAK2 V617Fhom mutations into JAK2 V617Fhet and JAK2 V617Fhom DC3. The JAK2 V617F mutation enhanced DC3 production and caused a bias toward erythrocytes and megakaryocytes. The patient-specific iPS cell-derived DC3 are expected to allow studying DC3 in human diseases and developing novel therapeutics.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fcell.2021.667304/fullTest; https://doaj.org/toc/2296-634XTest

الوصول الحر: https://doaj.org/article/066bc1a8ca6f4f6981093117e628c953Test

المؤلفون: Olivia Cypris, Joana Frobel, Shivam Rai, Julia Franzen, Stephanie Sontag, Roman Goetzke, Marcelo A. Szymanski de Toledo, Martin Zenke, Wolfgang Wagner

المصدر: Clinical Epigenetics, Vol 11, Iss 1, Pp 1-11 (2019)

مصطلحات موضوعية: DNA methylation, Epigenetic, Hematopoiesis, Induced pluripotent stem cells, Mesenchymal stromal cells, Stromal support, Medicine, Genetics, QH426-470

الوصف: Abstract Background Differentiation of induced pluripotent stem cells (iPSCs) toward hematopoietic progenitor cells (HPCs) raises high hopes for disease modeling, drug screening, and cellular therapy. Various differentiation protocols have been established to generate iPSC-derived HPCs (iHPCs) that resemble their primary counterparts in morphology and immunophenotype, whereas a systematic epigenetic comparison was yet elusive. Results In this study, we compared genome-wide DNA methylation (DNAm) patterns of iHPCs with various different hematopoietic subsets. After 20 days of in vitro differentiation, cells revealed typical hematopoietic morphology, CD45 expression, and colony-forming unit (CFU) potential. DNAm changes were particularly observed in genes that are associated with hematopoietic differentiation. On the other hand, the epigenetic profiles of iHPCs remained overall distinct from natural HPCs. Furthermore, we analyzed if additional co-culture for 2 weeks with syngenic primary mesenchymal stromal cells (MSCs) or iPSC-derived MSCs (iMSCs) further supports epigenetic maturation toward the hematopoietic lineage. Proliferation of iHPCs and maintenance of CFU potential was enhanced upon co-culture. However, DNAm profiles support the notion that additional culture expansion with stromal support did not increase epigenetic maturation of iHPCs toward natural HPCs. Conclusion Differentiation of iPSCs toward the hematopoietic lineage remains epigenetically incomplete. These results substantiate the need to elaborate advanced differentiation regimen while DNAm profiles provide a suitable measure to track this process.

وصف الملف: electronic resource

العلاقة: http://link.springer.com/article/10.1186/s13148-019-0617-1Test; https://doaj.org/toc/1868-7075Test; https://doaj.org/toc/1868-7083Test

الوصول الحر: https://doaj.org/article/a61a317ae52c426580ed9a1f5c50809eTest

المؤلفون: Stephanie Sontag, Malrun Förster, Kristin Seré, Martin Zenke

المصدر: Bio-Protocol, Vol 7, Iss 15 (2017)

مصطلحات موضوعية: Biology (General), QH301-705.5

الوصف: Induced pluripotent stem cells (iPS cells) are engineered stem cells, which exhibit properties very similar to embryonic stem cells (ES cells; Takahashi and Yamanaka, 2016). Both iPS cells and ES cells have an extraordinary self-renewal capacity and can differentiate into all cell types of our body, including hematopoietic stem/progenitor cells and dendritic cells (DC) derived thereof. This makes iPS cells particularly well suited for studying molecular mechanisms of diseases, drug discovery and regenerative therapy (Grskovic et al., 2011; Bellin et al., 2012; Robinton and Daley, 2012).DC are the major antigen presenting cells of the immune system and thus they are key players in modulating and directing immune responses (Merad et al., 2013). DC patrol peripheral and interface tissues (e.g., lung, intestine and skin) to detect invading pathogens, and upon activation they migrate to lymph nodes to activate and prime lymphocytes. DC comprise a phenotypically heterogeneous family with functionally specialized subsets (Schlitzer and Ginhoux, 2014). Generally, classical DC (cDC) and plasmacytoid DC (pDC) are distinguished, exhibiting a classical and plasma cell-like DC morphology, respectively. cDC recognize a multitude of pathogens and secrete proinflammatory cytokines upon activation, while pDC are specialized to detect intracellular pathogens and secrete type I interferons (Merad et al., 2013; Schlitzer and Ginhoux, 2014). cDC are further divided into cross-presenting cDC1 and conventional cDC2, in the human system referred to as CD141+ Clec9a+ cDC1 and CD1c+ CD14- cDC2. Human pDC are characterized as CD303+ CD304+ (Jongbloed et al., 2010; Joffre et al., 2012; Swiecki and Colonna, 2015). To investigate subset specification and function of human DC, we established a protocol to generate cDC1, cDC2 and pDC in vitro from human iPS cells (or ES cells) (Sontag et al., 2017). Therefore, we differentiated iPS cells (or ES cells), via mesoderm commitment and hemato-endothelial specification, into CD43+ CD31+ hematopoietic progenitors. Subsequently, those were seeded onto inactivated OP9 stromal cells with FLT3L, SCF, GM-CSF and IL-4 or FLT3L, SCF and GM-CSF to specify cDC1 and cDC2, or cDC1 and pDC, respectively.

وصف الملف: electronic resource

العلاقة: https://bio-protocol.org/en/bpdetail?id=2419&type=0Test; https://doaj.org/toc/2331-8325Test

الوصول الحر: https://doaj.org/article/083f14c4346e4edbb526adf57023ac08Test

المؤلفون: Martin M J Kirschner, Mirle Schemionek, Claudia Schubert, Nicolas Chatain, Stephanie Sontag, Susanne Isfort, Nadina Ortiz-Brüchle, Karla Schmitt, Luisa Krüger, Klaus Zerres, Martin Zenke, Tim H Brümmendorf, Steffen Koschmieder

المصدر: PLoS ONE, Vol 10, Iss 4, p e0123476 (2015)

مصطلحات موضوعية: Medicine, Science

الوصف: In order to assess the feasibility of amplicon-based parallel next generation sequencing (NGS) for the diagnosis of myeloproliferative neoplasms (MPN), we investigated multiplex-PCR of 212 amplicons covering genomic mutational hotspots in 48 cancer-related genes. Samples from 64 patients with MPN and five controls as well as seven (myeloid) cell lines were analyzed. Healthy donor and reactive erythrocytosis samples showed several frequent single-nucleotide polymorphisms (SNPs) but no known pathogenic mutation. Sequencing of the cell lines confirmed the presence of the known mutations. In the patient samples, JAK2 V617F was present in all PV, 4 of 10 ET, and 16 of 19 MF patients. The JAK2 V617F allele burden was different in the three groups (ET, 33+/-22%; PV 48+/-28% and MF 68+/- 29%). Further analysis detected both previously described and undescribed mutations (i.e., G12V NRAS, IDH1 R132H, E255G ABL, and V125G IDH1 mutations). One patient with lymphoid BC/Ph+ ALL who harbored a T315I ABL mutation and was treated with ponatinib was found to have developed a newly acquired V216M TP53 mutation (12% of transcripts) when becoming resistant to ponatinib. Ponatinib led to a decrease of ABL T315I positive transcripts from 47% before ponatinib treatment to 16% at the time of ponatinib resistance in this patient, suggesting that both TP53 and ABL mutations were present in the same clone and that the newly acquired TP53 mutation might have caused ponatinib resistance in this patient. In conclusion, amplicon-sequencing-based NGS allows simultaneous analysis of multiple MPN associated genes for diagnosis and during treatment and measurement of the mutant allele burden.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/65a2ac84af5c42c4accf73cea7939b2fTest

المؤلفون: Charlotte A Willmann, Hatim Hemeda, Lisa A Pieper, Michael Lenz, Jie Qin, Sylvia Joussen, Stephanie Sontag, Paul Wanek, Bernd Denecke, Herdit M Schüler, Martin Zenke, Wolfgang Wagner

المصدر: PLoS ONE, Vol 8, Iss 5, p e65324 (2013)

مصطلحات موضوعية: Medicine, Science

الوصف: Induced pluripotent stem cells (iPSCs) are usually clonally derived. The selection of fully reprogrammed cells generally involves picking of individual colonies with morphology similar to embryonic stem cells (ESCs). Given that fully reprogrammed cells are highly proliferative and escape from cellular senescence, it is conceivable that they outgrow non-pluripotent and partially reprogrammed cells during culture expansion without the need of clonal selection. In this study, we have reprogrammed human dermal fibroblasts (HDFs) with episomal plasmid vectors. Colony frequency was higher and size was larger when using murine embryonic fibroblasts (MEFs) as stromal support instead of HDFs or human mesenchymal stromal cells (MSCs). We have then compared iPSCs which were either clonally derived by manual selection of a single colony, or derived from bulk-cultures of all initial colonies. After few passages their morphology, expression of pluripotency markers, and gene expression profiles did not reveal any significant differences. Furthermore, clonally-derived and bulk-cultured iPSCs revealed similar in vitro differentiation potential towards the three germ layers. Therefore, manual selection of individual colonies does not appear to be necessary for the generation of iPSCs - this is of relevance for standardization and automation of cell culture procedures.

وصف الملف: electronic resource

العلاقة: http://europepmc.org/articles/PMC3667031?pdf=renderTest; https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/6f20a756e57b4e9c843e2563205aaed2Test

المؤلفون: Kai Ling Liang, Juliette Roels, Marieke Lavaert, Tom Putteman, Lena Boehme, Laurentijn Tilleman, Imke Velghe, Valentina Pegoretti, Inge Van de Walle, Stephanie Sontag, Jolien Vandewalle, Bart Vandekerckhove, Georges Leclercq, Pieter Van Vlierberghe, Claude Libert, Filip Van Nieuwerburgh, Roman Fischer, Roland E. Kontermann, Klaus Pfizenmaier, Gina Doody, Martin Zenke, Tom Taghon

المصدر: Nature Immunology. 24:474-486

مصطلحات موضوعية: Immunology, Immunology and Allergy

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::7fe8dd9eba6e89dff5ac443d4375330bTest
https://doi.org/10.1038/s41590-022-01417-6Test

المؤلفون: Michael Esquerré, Audrey Holtzinger, Nadja Wagner, Monika Braun, Mélanie Pichery, Stefanie Pfaender, Stephanie Sontag, Kathrin Haake, Michela Mirenda, Michael Paillasse, Davide Grandolfo, Chloé Beuraud, Mandy Richter, Philip Hublitz, Julien Bousquet, Marion Fabre, Mylène Gador, Daniel Sommermeyer, Tanja Schneider, Oriane Bombarde, Camille Esquerré, Loic Ysebaert, Fabien Despas, Matthias Austen, Andreas Scheel, Markus Dangl

المصدر: Cancer Research. 83:3203-3203

مصطلحات موضوعية: Cancer Research, Oncology

الوصف: Current autologous cell therapies, with blockbuster products on the market, have been leading for a decade to unprecedented clinical successes in patients with hematological malignancies. However, these patient-derived T-cell therapies are facing many challenges. The use of GMP iPSC lines to produce immune effector cells will reduce the complexity of the manufacturing process and will provide an unlimited source of starting material. The goal of the EVOcells Oncology platform is to offer a truly allogeneic cell therapy platform to treat a broad number of cancer patients with consistent quality and scalability of the final product. Besides, the versatility of our platform to produce different immune cell types combined to customized genetic engineering strategies will bring cell therapy to the level of personalized medicine. Our “off-the-shelf” cell therapy platform has already validated two pillars: iPSC-derived NK cells (iNK) and iPSC-derived Macrophages (iMACs). Through multiple genetic engineering strategies specific to each immune cell type, we are developing a comprehensive portfolio of cell therapy products to address specific tumor escape mechanism in liquid and solid tumors. Our initial effort aimed to develop these two innate immune cell types to propose efficacious cell therapies with an increased safety profile as they have low risk of graft-versus-host disease (GvHD) or CRS (Cytokine Release Syndrome). Thanks to the expression of a broad pattern of activatory receptors, iNK cells form Immunological Synapses with tumor cells leading in turn to efficient killing with and without addition of a CAR construct. Besides, we demonstrated the possibility to combine “naked” iNK cells with marketed therapeutic monoclonal antibodies (mAb) to further improve their efficacy. At the end of the differentiation process, iMACs are showing a M0 like phenotype with high plasticity allowing the in vitro differentiation of the cells towards either a M1 or a M2 polarization in response to the appropriate stimulations. iMACs produce key macrophages cytokines and are able to kill tumor cells via ADCP (Antibody-Dependent-Cell-Phagocytosis) mechanism when combined to a therapeutic mAb. Thanks to our collaboration with clinicians at the IUCT-Oncopole (Toulouse Cancer Hospital), we were able to identify appropriate cancer indications and further demonstrate in a translational fashion that both iNK and iMACs are able to kill primary resistant tumor cells which were isolated from patient’ samples. Taken together, these results are showing the versatility and the breadth of our EVOcells Oncology platform to produce a true arsenal of cell therapies and its potential for future clinical development. Citation Format: Michael Esquerré, Audrey Holtzinger, Nadja Wagner, Monika Braun, Mélanie Pichery, Stefanie Pfaender, Stephanie Sontag, Kathrin Haake, Michela Mirenda, Michael Paillasse, Davide Grandolfo, Chloé Beuraud, Mandy Richter, Philip Hublitz, Julien Bousquet, Marion Fabre, Mylène Gador, Daniel Sommermeyer, Tanja Schneider, Oriane Bombarde, Camille Esquerré, Loic Ysebaert, Fabien Despas, Matthias Austen, Andreas Scheel, Markus Dangl. EVOcells Oncology: Tailored genetic engineering of iPSC-derived immune effector cells and combination with the right biologic therapeutics result in optimal killing of primary tumor cells from patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3203.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::38551bec7bcaeeb0bc6d4973185b22a6Test
https://doi.org/10.1158/1538-7445.am2023-3203Test