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203. Mesenchymal Stem Cells Engineering: Microcapsules-Assisted Gene Transfection and Magnetic Cell Separation

Author

Muslimov, Albert R., primary, Timin, Alexander S., additional, Petrova, Aleksandra V., additional, Epifanovskaya, Olga S., additional, Shakirova, Alena I., additional, Lepik, Kirill V., additional, Gorshkov, Andrey, additional, Il’inskaja, Eugenia V., additional, Vasin, Andrey V., additional, Afanasyev, Boris V., additional, Fehse, Boris, additional, and Sukhorukov, Gleb B., additional

Published
2017
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206. Cetuximab Resistance in Head and Neck Cancer Is Mediated by EGFR-K521 Polymorphism

Author

Braig, Friederike, primary, Kriegs, Malte, additional, Voigtlaender, Minna, additional, Habel, Beate, additional, Grob, Tobias, additional, Biskup, Karina, additional, Blanchard, Veronique, additional, Sack, Markus, additional, Thalhammer, Anja, additional, Ben Batalla, Isabel, additional, Braren, Ingke, additional, Laban, Simon, additional, Danielczyk, Antje, additional, Goletz, Steffen, additional, Jakubowicz, Elzbieta, additional, Märkl, Bruno, additional, Trepel, Martin, additional, Knecht, Rainald, additional, Riecken, Kristoffer, additional, Fehse, Boris, additional, Loges, Sonja, additional, Bokemeyer, Carsten, additional, and Binder, Mascha, additional

Published
2017
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207. IL-33–Mediated Expansion of Type 2 Innate Lymphoid Cells Protects from Progressive Glomerulosclerosis

Author

Riedel, Jan-Hendrik, primary, Becker, Martina, additional, Kopp, Kerstin, additional, Düster, Mathis, additional, Brix, Silke R., additional, Meyer-Schwesinger, Catherine, additional, Kluth, Luis A., additional, Gnirck, Ann-Christin, additional, Attar, Madena, additional, Krohn, Sonja, additional, Fehse, Boris, additional, Stahl, Rolf A.K., additional, Panzer, Ulf, additional, and Turner, Jan-Eric, additional

Published
2017
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208. Clones with and without Sensitivity Towards Treatment In Vivo Co-Exist within the Tumor Cells of a Single Patient with ALL

Author

Finkenzeller, Cornelia, primary, Carlet, Michela, additional, Vosberg, Sebastian, additional, Ziegenhain, Christoph, additional, Neumann, Martin, additional, Riecken, Kristoffer, additional, Cornils, Kerstin, additional, Fehse, Boris, additional, Baldus, Claudia D., additional, Enard, Wolfgang, additional, Greif, Philipp A., additional, and Jeremias, Irmela, additional

Published
2016
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212. Mesenchymal Stem Cells Engineering: Microcapsules-Assisted Gene Transfection and Magnetic Cell Separation

Author

Muslimov, Albert R., Timin, Alexander S., Petrova, Aleksandra V., Epifanovskaya, Olga S., Shakirova, Alena I., Lepik, Kirill V., Gorshkov, Andrey, Il’inskaja, Eugenia V., Vasin, Andrey V., Afanasyev, Boris V., Fehse, Boris, and Sukhorukov, Gleb B.

Abstract

Stem cell engineeringthe manipulation and functionalization of stem cells involving genetic modificationcan significantly expand their applicability for cell therapy in humans. Toward this aim, reliable, standardized, and cost-effective methods for cell manipulation are required. Here we explore the potential of magnetic multilayer capsules to serve as a universal platform for nonviral gene transfer, stem cell magnetization, and magnetic cell separation to improve gene transfer efficiency. In particular, the following experiments were performed: (i) a study of the process of internalization of magnetic capsules into stem cells, including capsule co-localization with established markers of endo-lysosomal pathway; (ii) characterization and quantification of capsule uptake with confocal microscopy, electron microscopy, and flow cytometry; (iii) intracellular delivery of messenger RNA and separation of gene-modified cells by magnetic cell sorting (MACS); and (iv) analysis of the influence of capsules on cell proliferation potential. Importantly, based on the internalization of magnetic capsules, transfected cells became susceptible to external magnetic fields, which made it easy to enrich gene-modified cells using MACS (purity ∼95%), and also to influence their migration behavior. In summary, our results underline the high potential of magnetic capsules in stem cell functionalization, namely (i) to increase gene-transfer efficiency and (ii) to facilitate enrichment and targeting of transfected cells. Finally, we did not observe a negative impact of the capsules used on the proliferative capacity of stem cells, proving their high biocompatibility.

Published
2024
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213. Mutation Clearance of Driver Mutations after Transplantation for Myelofibrosis Predicts Outcome

Author

Gagelmann, Nico, Quarder, Marie, Badbaran, Anita, Wolschke, Christine, Rathje, Kristin, Schäfersküpper, Mathias, Kunte, Ameya Shrinivas, Klyuchnikov, Evgeny, Massoud, Radwan, Richter, Johanna, Janson, Dietlinde, Fehse, Boris, Ayuk, Francis A., and Kroeger, Nicolaus

Abstract

Myelofibrosis is one of the Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) characterized by clonal myeloproliferation. Allogeneic hematopoietic stem-cell transplantation is the only potentially curative treatment for patients with myelofibrosis. With that, it can resolve fibrosis and lead to complete loss of the clonal burden. More than 90% of myelofibrosis patients harbor driver mutations in one of the 3 genes JAK2, CALR, and MPL, with JAK2mutations being associated with worse outcomes.

Published
2023
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223. Massive Clonal Selection and Transiently Contributing Clones During Expansion of Mesenchymal Stem Cell Cultures Revealed by Lentiviral RGB-Barcode Technology

Author

Selich, Anton, primary, Daudert, Jannik, additional, Hass, Ralf, additional, Philipp, Friederike, additional, von Kaisenberg, Constantin, additional, Paul, Gabi, additional, Cornils, Kerstin, additional, Fehse, Boris, additional, Rittinghausen, Susanne, additional, Schambach, Axel, additional, and Rothe, Michael, additional

Published
2016
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224. Impact of Molecular Genetics on Disease-Free Survival in Myelofibrosis Patients Following Allogeneic Stem Cell Transplantation

Author

Kroeger, Nicolaus, primary, Panagiota, Victoria, additional, Zabelina, Tatjana, additional, Araujo Cruz, Michelle Maria, additional, Shahswar, Rabia, additional, Badbaran, Anita, additional, Triviai, Ioanna N, additional, Ayuk, Francis, additional, Gehlhaar, Marten, additional, Wolschke, Christine, additional, Bollin, Robin, additional, Lehmann, Ulrich, additional, Koenecke, Christian, additional, Chaturvedi, Anuhar, additional, Alchalby, Haefaa, additional, Stadler, Michael, additional, Eder, Matthias, additional, Christopeit, Maximilian, additional, Göhring, Gudrun, additional, Koenigsmann, Michael, additional, Schlegelberger, Brigitte, additional, Kreipe, Hans Heinrich, additional, Ganser, Arnold, additional, Fehse, Boris, additional, Thol, Felicitas, additional, and Heuser, Michael, additional

Published
2015
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226. Impact of Minimal Residual Disease after Allografting Detected By JAK2V617F, MPL or Calreticulin in Myelofibrosis Patients

Author

Kroeger, Nicolaus, primary, Badbaran, Anita, additional, Zabelina, Tatjana, additional, Christopeit, Maximilian, additional, Wolschke, Christine, additional, Ayuk, Francis, additional, Zander, Axel R., additional, Alchalby, Haefaa, additional, Bacher, Ulrike, additional, Triviai, Ioanna N, additional, and Fehse, Boris, additional

Published
2015
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229. 1. Kernaussagen und Handlungsempfehlungen

Author

Müller-Röber, Bernd, Hucho, Ferdinand, Budisa, Nediljko, Fehse, Boris, Hampel, Jürgen, Köchy, Kristian, Reich, Jens, Rheinberger, Hans-Jörg, Ropers, Hans-Hilger, Taupitz, Jochen, and Walter, Jörn

Subjects
ddc:570
Published
2013

231. High Bone Turnover in Mice Carrying a Pathogenic Notch2 Mutation Causing Hajdu‐Cheney Syndrome.

Author

Vollersen, Nele, Rolvien, Tim, Jeschke, Anke, Oheim, Ralf, Amling, Michael, Schinke, Thorsten, Yorgan, Timur Alexander, Hermans‐Borgmeyer, Irm, Cornils, Kerstin, Fehse, Boris, and Triviai, Ioanna

Abstract

ABSTRACT: Hajdu‐Cheney syndrome (HCS) is a rare autosomal‐dominant disorder primarily characterized by acro‐osteolysis and early‐onset osteoporosis. Genetically, HCS is caused by nonsense or deletion mutations within exon 34 of the NOTCH2 gene, resulting in premature translational termination and production of C‐terminally truncated NOTCH2 proteins that are predicted to activate NOTCH2‐dependent signaling. To understand the role of Notch2 in bone remodeling, we developed a mouse model of HCS by introducing a pathogenic mutation (6272delT) into the murine Notch2 gene. By μCT and undecalcified histology, we observed generalized osteopenia in two independent mouse lines derived by injection of different targeted embryonic stem (ES) cell clones, yet acro‐osteolysis did not occur until the age of 52 weeks. Cellular and dynamic histomorphometry revealed a high bone turnover situation in Notch2+/HCS mice, since osteoblast and osteoclast indices were significantly increased compared with wild‐type littermates. Whereas ex vivo cultures failed to uncover cell‐autonomous gain‐of‐functions within the osteoclast or osteoblast lineage, an unbiased RNA sequencing approach identified Tnfsf11 and Il6 as Notch‐signaling target genes in bone marrow cells cultured under osteogenic conditions. Because we further observed that the high‐turnover pathology of Notch2+/HCS mice was fully normalized by alendronate treatment, our results demonstrate that mutational activation of Notch2 does not directly control osteoblast activity but favors a pro‐osteoclastic gene expression pattern, which in turn triggers high bone turnover. © 2017 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Published
2018
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232. Optimization of the indications for allogeneic stem cell transplantation in Acute Myeloid Leukemia based on interactive diagnostic strategies

Author

Hartwig, Maite, Zander, Axel R., Haferlach, Torsten, Fehse, Boris, Kröger, Nicolaus, and Bacher, Ulrike

Subjects
surgical procedures, operative, hemic and lymphatic diseases, ddc:610, human activities
Abstract

The indications for allogeneic stem cell transplantation (SCT) in Acute Myeloid Leukemia (AML) represent a real challenge due to the clinical and genetic heterogeneity of the disorder. Therefore, an optimized indication for SCT in AML first requires the determination of the individual relapse risk based on diverse chromosomal and molecular prognosis-defining aberrations. A broad panel of diagnostic methods is needed to allow such subclassification and prognostic stratification: cytomorphology, cytogenetics, molecular genetics, and immunophenotyping by multiparameter flow cytometry. These methods should not be seen as isolated techniques but as parts of an integral network with hierarchies and interactions. Examples for a poor risk constellation as a clear indication for allogeneic SCT are provided by anomalies of chromosome 7, complex aberrations, or FLT3-length mutations. In contrast, the favorable reciprocal translocations such as the t(15;17)/PML-RARA or t(8;21)/AML1-ETO are not indications for SCT in first remission due to the rather good prognosis after standard therapy. Further, the indication for SCT should include the results of minimal residual disease (MRD) diagnostics by polymerase chain reaction (PCR) or flow cytometry. New aspects for a safe and fast risk stratification as basis for an optimized indication for SCT in AML might be provided by novel technologies such as microarray-based gene expression profiling. Keywords: Acute Myeloid Leukemia (AML), Allogeneic Stem Cell Transplantation (SCT), Indication, Cytogenetics, Polymerase Chain Reaction (PCR)

Published
2011

233. Second Gene Technology Report

Author

Müller-Röber, Bernd, Boysen, Mathias, Fehse, Boris, Hucho, Ferdinand, Köchy, Kristian, Reich, Jens, Rheinberger, Hans-Jörg, Ropers, Hans-Hilger, Sperling, Karl, and Wobus, Anna M.

Subjects
Gentherapie, Bioethik, ddc:570, Gentechnologie, Indikator, Pflanzenzüchtung, Agrarforschung, Stammzelle, Grundlagenforschung
Abstract

Wissenschaftliche und technologische Entwicklungen, hitzig geführte öffentliche Debatten um Chancen und Risiken oder die wechselnde Brisanz einzelner Themen prägen nach wie vor die kontroversen Auseinandersetzungen um die verschiedenen Anwendungen der Gentechnologie in Deutschland. Mit dem zweiten Gentechnologiebericht legt die gleichnamige interdisziplinäre Arbeitsgruppe der Berlin-Brandenburgischen Akademie der Wissenschaften, vier Jahre nach dem Erscheinen ihres ersten Berichts, wieder ihr umfassendes Monitoring zu den aktuellen Entwicklungen auf dem Gebiet der Gentechnologie vor. In bewährt interdisziplinärer Weise wird der aktuelle Stand von Wissenschaft und Technik in den verschiedenen Gebieten der Gentechnologie analysiert. Das Indikatoren-gestützte Vorgehen, das hierfür in den letzten Jahren etablierte wurde, erfährt dabei eine konsequente Fortführung. In Überblicksartikeln werden vier Themenbereiche betrachtet: die Forschung an pluripotenten humanen Stammzellen, die molekulargenetische Diagnostik in der Humanmedizin, die somatische Gentherapie sowie der Gentechnologieeinsatz in Pflanzenzüchtung und Agrarwirtschaft. Zwei Querschnittsthemen, eine allgemeine Darstellung aktueller wissenschaftlicher und technischer Entwicklungen in der Grundlagenforschung sowie die Vorstellung eines übergreifenden ethischen Kategoriensystems für gentechnologische Anwendungen, runden den Bericht ab. The second German Gene Technology Report discusses, as did its predecessor, the fields of basic research, molecular diagnosis in human medicine, and green gene technology, i.e., the application of gene technology in plant breeding and agriculture. New additions are research on pluripotent human stem cells, as well as the field of somatic gene therapy, to which individual volumes have already been dedicated in the last years. Also new is the inclusion of a comprehensive chapter on ethics, which is unique in describing in this form a system of general ethical categories for all applications of gene technology, thus departing from the classical method of "ethical domains" for individual forms of application.

Published
2010

234. Corrigendum to “Targeting species D adenoviruses replication to counteract the epidemic keratoconjunctivitis” [Biochimie 113C (2015) 10–16]

Author

Nikitenko, Natalia A., primary, Speiseder, Thomas, additional, Groitl, Peter, additional, Spirin, Pavel V., additional, Prokofjeva, Maria M., additional, Lebedev, Timofey D., additional, Rubtsov, Petr M., additional, Lam, Elena, additional, Riecken, Kristoffer, additional, Fehse, Boris, additional, Dobner, Thomas, additional, and Prassolov, Vladimir S., additional

Published
2015
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235. Fibroblastic colony forming units (CFU-F) within adherent cell layer from long-term bone marrow cultures correspond to the progeny of distinct mesenchymal precursor cells

Author

Bigildeev, ALexey, primary, Sats, Natalia, additional, Shipounova, Irina, additional, Petinati, Natalia, additional, Surin, Vadim, additional, Cornils, Kerstin, additional, Riecken, Kristoffer, additional, Aranyossy, Tim, additional, Fehse, Boris, additional, and Drize, Nina, additional

Published
2015
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238. Targeting species D adenoviruses replication to counteract the epidemic keratoconjunctivitis

Author

Nikitenko, Natalia A., primary, Speiseder, Thomas, additional, Groitl, Peter, additional, Spirin, Pavel V., additional, Prokofjeva, Maria M., additional, Lebedev, Timofey D., additional, Rubtsov, Petr M., additional, Lam, Elena, additional, Riecken, Kristoffer, additional, Fehse, Boris, additional, Dobner, Thomas, additional, and Prassolov, Vladimir S., additional

Published
2015
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240. Epidermal growth factor receptor mutations may confer resistance or cross-resistance to cetuximab and panitumumab and can be detected in circulating tumor DNA.

Author

Binder, Mascha, primary, Braig, Friederike, additional, Schieferdecker, Aneta, additional, Schulte, Alexander, additional, Stein, Alexander, additional, Grob, Tobias, additional, Kriegs, Malte, additional, Engel, Erik, additional, Vanhoefer, Udo J., additional, Loges, Sonja, additional, Riecken, Kristoffer, additional, Fehse, Boris, additional, and Bokemeyer, Carsten, additional

Published
2015
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243. Epidermal growth factor receptor mutation mediates cross-resistance to panitumumab and cetuximab in gastrointestinal cancer

Author

Braig, Friederike, primary, März, Manuela, additional, Schieferdecker, Aneta, additional, Schulte, Alexander, additional, Voigt, Mareike, additional, Stein, Alexander, additional, Grob, Tobias, additional, Alawi, Malik, additional, Indenbirken, Daniela, additional, Kriegs, Malte, additional, Engel, Erik, additional, Vanhoefer, Udo, additional, Grundhoff, Adam, additional, Loges, Sonja, additional, Riecken, Kristoffer, additional, Fehse, Boris, additional, Bokemeyer, Carsten, additional, and Binder, Mascha, additional

Published
2015
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244. Cyclooxygenase-2 blockade can improve efficacy of VEGF-targeting drugs

Author

Ben-Batalla, Isabel, primary, Cubas-Cordova, Miguel, additional, Udonta, Florian, additional, Wroblewski, Mark, additional, Waizenegger, Jonas S., additional, Janning, Melanie, additional, Sawall, Stefanie, additional, Gensch, Victoria, additional, Zhao, Lin, additional, Martinez-Zubiaurre, Iñigo, additional, Riecken, Kristoffer, additional, Fehse, Boris, additional, Pantel, Klaus, additional, Bokemeyer, Carsten, additional, and Loges, Sonja, additional

Published
2015
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245. Selectins Mediate Small Cell Lung Cancer Systemic Metastasis

Author

Massachusetts Institute of Technology. Department of Chemistry, Bruns, Oliver Thomas, Heidemann, Franziska, Schildt, Anna, Schmid, Katharina, Riecken, Kristoffer, Jung, Caroline, Ittrich, Harald, Wicklein, Daniel, Reimer, Rudolph, Fehse, Boris, Heeren, Joerg, Lüers, Georg, Schumacher, Udo, Heine, Markus, Massachusetts Institute of Technology. Department of Chemistry, Bruns, Oliver Thomas, Heidemann, Franziska, Schildt, Anna, Schmid, Katharina, Riecken, Kristoffer, Jung, Caroline, Ittrich, Harald, Wicklein, Daniel, Reimer, Rudolph, Fehse, Boris, Heeren, Joerg, Lüers, Georg, Schumacher, Udo, and Heine, Markus

Abstract

Metastasis formation is the major reason for the extremely poor prognosis in small cell lung cancer (SCLC) patients. The molecular interaction partners regulating metastasis formation in SCLC are largely unidentified, however, from other tumor entities it is known that tumor cells use the adhesion molecules of the leukocyte adhesion cascade to attach to the endothelium at the site of the future metastasis. Using the human OH-1 SCLC line as a model, we found that these cells expressed E- and P-selectin binding sites, which could be in part attributed to the selectin binding carbohydrate motif sialyl Lewis A. In addition, protein backbones known to carry these glycotopes in other cell lines including PSGL-1, CD44 and CEA could be detected in in vitro and in vivo grown OH1 SCLC cells. By intravital microscopy of murine mesenterial vasculature we could capture SCLC cells while rolling along vessel walls demonstrating that SCLC cells mimic leukocyte rolling behavior in terms of selectin and selectin ligand interaction in vivo indicating that this mechanism might indeed be important for SCLC cells to seed distant metastases. Accordingly, formation of spontaneous distant metastases was reduced by 50% when OH-1 cells were xenografted into E-/P-selectin-deficient mice compared with wild type mice (p = 0.0181). However, as metastasis formation was not completely abrogated in selectin deficient mice, we concluded that this adhesion cascade is redundant and that other molecules of this cascade mediate metastasis formation as well. Using several of these adhesion molecules as interaction partners presumably make SCLC cells so highly metastatic., Bundesministerium für Wissenschaft und Forschung (TOMCAT, grant number 01EZ0824; http://www.bmbf.de/), Landesexzellenzinitiative Hamburg (Nanotechnology in Medicine – NAME)

Published
2014

247. Prognostic Impact of Splicing Factor Mutations in Patients with Myelofibrosis Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Author

Panagiota, Victoria, primary, Heuser, Michael, additional, Araujo Cruz, Michelle Maria, additional, Badbaran, Anita, additional, Shahswar, Rabia, additional, Triviai, Ioanna N, additional, Fehse, Boris, additional, Alchalby, Haefaa, additional, Lehmann, Ulrich, additional, Koenecke, Christian, additional, Chaturvedi, Anuhar, additional, Stadler, Michael, additional, Eder, Matthias, additional, Göhring, Gudrun, additional, Koenigsmann, Michael, additional, Schlegelberger, Brigitte, additional, Kreipe, Hans Heinrich, additional, Ganser, Arnold, additional, Thol, Felicitas, additional, and Kröger, Nicolaus, additional

Published
2014
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248. Fetomaternal Microchimerism Is Associated with Better Outcome in Haploidentical Hematopoietic Stem Cell Transplantation

Author

Kruchen, Anne, primary, Stahl, Tanja, additional, Gieseke, Friederike, additional, Binder, Thomas MC, additional, Oezcan, Zakir, additional, Meisel, Roland, additional, Kreyenberg, Hermann, additional, Bader, Peter, additional, Gruhn, Bernd, additional, Greil, Johann, additional, Pfeiffer, Matthias, additional, Doering, Michaela, additional, Handgretinger, Rupert, additional, Fehse, Boris, additional, and Mueller, Ingo, additional

Published
2014
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