TY - JOUR A1 - Schütz, Burkhard A1 - Jurastow, Innokentij A1 - Bader, Sandra A1 - Ringer, Cornelia A1 - Engelhardt, Jakob von A1 - Chubanov, Vladimir A1 - Gudermann, Thomas A1 - Diener, Martin A1 - Kummer, Wolfgang A1 - Krasteva-Christ, Gabriela A1 - Weihe, Eberhard T1 - Chemical coding and chemosensory properties of cholinergic brush cells in the mouse gastrointestinal and biliary tract JF - Frontiers in Physiology N2 - The mouse gastro-intestinal and biliary tract mucosal epithelia harbor choline acetyltransferase (ChAT)-positive brush cells with taste cell-like traits. With the aid of two transgenic mouse lines that express green fluorescent protein (EGFP) under the control of the ChAT promoter (EGFP\(^{ChAT}\)) and by using in situ hybridization and immunohistochemistry we found that EGFP\(^{ChAT}\) cells were clustered in the epithelium lining the gastric groove. EGFP\(^{ChAT}\) cells were numerous in the gall bladder and bile duct, and found scattered as solitary cells along the small and large intestine. While all EGFP\(^{ChAT}\) cells were also ChAT-positive, expression of the high-affinity choline transporter (ChT1) was never detected. Except for the proximal colon, EGFP\(^{ChAT}\) cells also lacked detectable expression of the vesicular acetylcholine transporter (VAChT). EGFP\(^{ChAT}\) cells were found to be separate from enteroendocrine cells, however they were all immunoreactive for cytokeratin 18 (CK18), transient receptor potential melastatin-like subtype 5 channel (TRPM5), and for cyclooxygenases 1 (COX1) and 2 (COX2). The ex vivo stimulation of colonic EGFP\(^{ChAT}\) cells with the bitter substance denatonium resulted in a strong increase in intracellular calcium, while in other epithelial cells such an increase was significantly weaker and also timely delayed. Subsequent stimulation with cycloheximide was ineffective in both cell populations. Given their chemical coding and chemosensory properties, EGFP\(^{ChAT}\) brush cells thus may have integrative functions and participate in induction of protective reflexes and inflammatory events by utilizing ACh and prostaglandins for paracrine signaling. KW - vesicular acetylcholine transporter KW - nonneuronal acetylcholine KW - nervous system KW - functional characterization KW - cholinergic KW - taste receptor cells KW - enteroendocrine cells KW - gene locus KW - tuft cells KW - transgenic mice KW - expression KW - brush cell KW - ChAT KW - VAChT KW - ChT1 KW - intestine KW - gall bladder KW - bile duct Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-143550 VL - 6 IS - 87 ER - TY - JOUR A1 - Salzmann-Manrique, Emilia A1 - Bremm, Melanie A1 - Huenecke, Sabine A1 - Stech, Milena A1 - Orth, Andreas A1 - Eyrich, Matthias A1 - Schulz, Ansgar A1 - Esser, Ruth A1 - Klingebiel, Thomas A1 - Bader, Peter A1 - Herrmann, Eva A1 - Koehl, Ulrike T1 - Joint Modeling of Immune Reconstitution Post Haploidentical Stem Cell Transplantation in Pediatric Patients With Acute Leukemia Comparing CD34(+)-Selected to CD3/CD19-Depleted Grafts in a Retrospective Multicenter Study JF - frontiers in Immunology N2 - Rapid immune reconstitution (IR) following stem cell transplantation (SCT) is essential for a favorable outcome. The optimization of graft composition should not only enable a sufficient IR but also improve graft vs. leukemia/tumor effects, overcome infectious complications and, finally, improve patient survival. Especially in haploidentical SCT, the optimization of graft composition is controversial. Therefore, we analyzed the influence of graft manipulation on IR in 40 patients with acute leukemia in remission. We examined the cell recovery post haploidentical SCT in patients receiving a CD34(+)-selected or CD3/CD19-depleted graft, considering the applied conditioning regimen. We used joint model analysis for overall survival (OS) and analyzed the dynamics of age-adjusted leukocytes; lymphocytes; monocytes; CD3(+), CD3(+) CD4(+), and CD3(+) CD8(+) T cells; natural killer (NK) cells; and B cells over the course of time after SCT. Lymphocytes, NK cells, and B cells expanded more rapidly after SCT with CD34(+)-selected grafts (P = 0.036, P = 0.002, and P < 0.001, respectively). Contrarily, CD3(+) CD4(+) helper T cells recovered delayer in the CD34 selected group (P = 0.026). Furthermore, reduced intensity conditioning facilitated faster immune recovery of lymphocytes and T cells and their subsets (P < 0.001). However, the immune recovery for NK cells and B cells was comparable for patients who received reduced-intensity or full preparative regimens. Dynamics of all cell types had a significant influence on OS, which did not differ between patients receiving CD34(+)-selected and those receiving CD3/CD19-depleted grafts. In conclusion, cell reconstitution dynamics showed complex diversity with regard to the graft manufacturing procedure and conditioning regimen. KW - immune reconstitution KW - allogeneic stem cell transplantation KW - CD34 selection KW - CD3/19 depletion KW - children Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227302 VL - 9 ER - TY - JOUR A1 - Bonig, Halvard A1 - Kuçi, Zyrafete A1 - Kuçi, Selim A1 - Bakhtiar, Shahrzad A1 - Basu, Oliver A1 - Bug, Gesine A1 - Dennis, Mike A1 - Greil, Johann A1 - Barta, Aniko A1 - Kállay, Krisztián M. A1 - Lang, Peter A1 - Lucchini, Giovanna A1 - Pol, Raj A1 - Schulz, Ansgar A1 - Sykora, Karl-Walter A1 - Teichert von Luettichau, Irene A1 - Herter-Sprie, Grit A1 - Ashab Uddin, Mohammad A1 - Jenkin, Phil A1 - Alsultan, Abdulrahman A1 - Buechner, Jochen A1 - Stein, Jerry A1 - Kelemen, Agnes A1 - Jarisch, Andrea A1 - Soerensen, Jan A1 - Salzmann-Manrique, Emilia A1 - Hutter, Martin A1 - Schäfer, Richard A1 - Seifried, Erhard A1 - Paneesha, Shankara A1 - Novitzky-Basso, Igor A1 - Gefen, Aharon A1 - Nevo, Neta A1 - Beutel, Gernot A1 - Schlegel, Paul-Gerhardt A1 - Klingebiel, Thomas A1 - Bader, Peter T1 - Children and adults with Refractory acute Graft-versus-Host Disease respond to treatment with the Mesenchymal Stromal cell preparation “MSC-FFM”—Outcome report of 92 patients JF - Cells N2 - (1) Background: Refractory acute graft-versus-host disease (R-aGvHD) remains a leading cause of death after allogeneic stem cell transplantation. Survival rates of 15% after four years are currently achieved; deaths are only in part due to aGvHD itself, but mostly due to adverse effects of R-aGvHD treatment with immunosuppressive agents as these predispose patients to opportunistic infections and loss of graft-versus-leukemia surveillance resulting in relapse. Mesenchymal stromal cells (MSC) from different tissues and those generated by various protocols have been proposed as a remedy for R-aGvHD but the enthusiasm raised by initial reports has not been ubiquitously reproduced. (2) Methods: We previously reported on a unique MSC product, which was generated from pooled bone marrow mononuclear cells of multiple third-party donors. The products showed dose-to-dose equipotency and greater immunosuppressive capacity than individually expanded MSCs from the same donors. This product, MSC-FFM, has entered clinical routine in Germany where it is licensed with a national hospital exemption authorization. We previously reported satisfying initial clinical outcomes, which we are now updating. The data were collected in our post-approval pharmacovigilance program, i.e., this is not a clinical study and the data is high-level and non-monitored. (3) Results: Follow-up for 92 recipients of MSC-FFM was reported, 88 with GvHD ≥°III, one-third only steroid-refractory and two-thirds therapy resistant (refractory to steroids plus ≥2 additional lines of treatment). A median of three doses of MSC-FFM was administered without apparent toxicity. Overall response rates were 82% and 81% at the first and last evaluation, respectively. At six months, the estimated overall survival was 64%, while the cumulative incidence of death from underlying disease was 3%. (4) Conclusions: MSC-FFM promises to be a safe and efficient treatment for severe R-aGvHD. KW - graft-versus host KW - transplantation KW - mesenchymal stromal cell KW - cell therapy KW - hospital exemption KW - steroid-resistant aGvHD KW - refractory aGvHD Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193878 SN - 2073-4409 VL - 8 IS - 12 ER - TY - JOUR A1 - Käthner, Ivo A1 - Bader, Thomas A1 - Pauli, Paul T1 - Heat pain modulation with virtual water during a virtual hand illusion JF - Scientific Reports N2 - Immersive virtual reality is a powerful method to modify the environment and thereby influence experience. The present study used a virtual hand illusion and context manipulation in immersive virtual reality to examine top-down modulation of pain. Participants received painful heat stimuli on their forearm and placed an embodied virtual hand (co-located with their real one) under a virtual water tap, which dispensed virtual water under different experimental conditions. We aimed to induce a temperature illusion by a red, blue or white light suggesting warm, cold or no virtual water. In addition, the sense of agency was manipulated by allowing participants to have high or low control over the virtual hand’s movements. Most participants experienced a thermal sensation in response to the virtual water and associated the blue and red light with cool/cold or warm/hot temperatures, respectively. Importantly, the blue light condition reduced and the red light condition increased pain intensity and unpleasantness, both compared to the control condition. The control manipulation influenced the sense of agency, but did not influence pain ratings. The large effects revealed in our study suggest that context effects within an embodied setting in an immersive virtual environment should be considered within VR based pain therapy. KW - Cognitive neuroscience KW - Neuroscience KW - Psychology Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202221 VL - 9 ER -