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Type: article × search.filters.applied.f.series: Scientific Reports 7 (2017), Nr. 1 × WGL Institute: IPF ×

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Now showing 1 - 7 of 7
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    Cryogel-supported stem cell factory for customized sustained release of bispecific antibodies for cancer immunotherapy
    (London : Nature Publishing Group, 2017) Aliperta, Roberta; Welzel, Petra B.; Bergmann, Ralf; Freudenberg, Uwe; Berndt, Nicole; Feldmann, Anja; Arndt, Claudia; Koristka, Stefanie; Stanzione, Marcello; Cartellieri, Marc; Ehninger, Armin; Ehninger, Gerhard; Werner, Carsten; Pietzsch, Jens; Steinbach, Jörg; Bornhäuser, Martin; Bachmann, Michael P.
    Combining stem cells with biomaterial scaffolds provides a promising strategy for the development of drug delivery systems. Here we propose an innovative immunotherapeutic organoid by housing human mesenchymal stromal cells (MSCs), gene-modified for the secretion of an anti-CD33-anti-CD3 bispecific antibody (bsAb), in a small biocompatible star-shaped poly(ethylene glycol)-heparin cryogel scaffold as a transplantable and low invasive therapeutic machinery for the treatment of acute myeloid leukemia (AML). The macroporous biohybrid cryogel platform displays effectiveness in supporting proliferation and survival of bsAb-releasing-MSCs overtime in vitro and in vivo, avoiding cell loss and ensuring a constant release of sustained and detectable levels of bsAb capable of triggering T-cell-mediated anti-tumor responses and a rapid regression of CD33 + AML blasts. This therapeutic device results as a promising and safe alternative to the continuous administration of short-lived immunoagents and paves the way for effective bsAb-based therapeutic strategies for future tumor treatments.
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    Zebrafish In-Vivo Screening for Compounds Amplifying Hematopoietic Stem and Progenitor Cells: - Preclinical Validation in Human CD34+ Stem and Progenitor Cells
    (London : Nature Publishing Group, 2017) Arulmozhivarman, Guruchandar; Kräter, Martin; Wobus, Manja; Friedrichs, Jens; Bejestani, Elham Pishali; Müller, Katrin; Lambert, Katrin; Alexopoulou, Dimitra; Dahl, Andreas; Stöter, Martin; Bickle, Marc; Shayegi, Nona; Hampe, Jochen; Stölzel, Friedrich; Brand, Michael; von Bonin, Malte; Bornhäuser, Martin
    The identification of small molecules that either increase the number and/or enhance the activity of human hematopoietic stem and progenitor cells (hHSPCs) during ex vivo expansion remains challenging. We used an unbiased in vivo chemical screen in a transgenic (c-myb:EGFP) zebrafish embryo model and identified histone deacetylase inhibitors (HDACIs), particularly valproic acid (VPA), as significant enhancers of the number of phenotypic HSPCs, both in vivo and during ex vivo expansion. The long-term functionality of these expanded hHSPCs was verified in a xenotransplantation model with NSG mice. Interestingly, VPA increased CD34+ cell adhesion to primary mesenchymal stromal cells and reduced their in vitro chemokine-mediated migration capacity. In line with this, VPA-treated human CD34+ cells showed reduced homing and early engraftment in a xenograft transplant model, but retained their long-term engraftment potential in vivo, and maintained their differentiation ability both in vitro and in vivo. In summary, our data demonstrate that certain HDACIs lead to a net expansion of hHSPCs with retained long-term engraftment potential and could be further explored as candidate compounds to amplify ex-vivo engineered peripheral blood stem cells.
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    Solid-state 31P and 1H chemical MR micro-imaging of hard tissues and biomaterials with magic angle spinning at very high magnetic field
    (London : Nature Publishing Group, 2017) Yon, Maxime; Sarou-Kanian, Vincent; Scheler, Ulrich; Bouler, Jean-Michel; Bujoli, Bruno; Massiot, Dominique; Fayon, Franck
    In this work, we show that it is possible to overcome the limitations of solid-state MRI for rigid tissues due to large line broadening and short dephasing times by combining Magic Angle Spinning (MAS) with rotating pulsed field gradients. This allows recording ex vivo 31P 3D and 2D slice-selected images of rigid tissues and related biomaterials at very high magnetic field, with greatly improved signal to noise ratio and spatial resolution when compared to static conditions. Cross-polarization is employed to enhance contrast and to further depict spatially localized chemical variations in reduced experimental time. In these materials, very high magnetic field and moderate MAS spinning rate directly provide high spectral resolution and enable the use of frequency selective excitation schemes for chemically selective imaging. These new possibilities are exemplified with experiments probing selectively the 3D spatial distribution of apatitic hydroxyl protons inside a mouse tooth with attached jaw bone with a nominal isotropic resolution nearing 100 μm.
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    Bone marrow niche-mimetics modulate HSPC function via integrin signaling
    (London : Nature Publishing Group, 2017) Kräter, Martin; Jacobi, Angela; Otto, Oliver; Tietze, Stefanie; Müller, Katrin; Poitz, David M.; Palm, Sandra; Zinna, Valentina M.; Biehain, Ulrike; Wobus, Manja; Chavakis, Triantafyllos; Werner, Carsten; Guck, Jochen; Bornhauser, Martin
    The bone marrow (BM) microenvironment provides critical physical cues for hematopoietic stem and progenitor cell (HSPC) maintenance and fate decision mediated by cell-matrix interactions. However, the mechanisms underlying matrix communication and signal transduction are less well understood. Contrary, stem cell culture is mainly facilitated in suspension cultures. Here, we used bone marrow-mimetic decellularized extracellular matrix (ECM) scaffolds derived from mesenchymal stromal cells (MSCs) to study HSPC-ECM interaction. Seeding freshly isolated HSPCs adherent (AT) and non-adherent (SN) cells were found. We detected enhanced expansion and active migration of AT-cells mediated by ECM incorporated stromal derived factor one. Probing cell mechanics, AT-cells displayed naïve cell deformation compared to SN-cells indicating physical recognition of ECM material properties by focal adhesion. Integrin αIIb (CD41), αV (CD51) and β3 (CD61) were found to be induced. Signaling focal contacts via ITGβ3 were identified to facilitate cell adhesion, migration and mediate ECM-physical cues to modulate HSPC function.
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    Plasmonic nanomeshes: Their ambivalent role as transparent electrodes in organic solar cells
    (London : Nature Publishing Group, 2017) Stelling, Christian; Singh, Chetan R.; Karg, Matthias; König, Tobias A.F.; Thelakkat, Mukundan; Retsch, Markus
    In this contribution, the optical losses and gains attributed to periodic nanohole array electrodes in polymer solar cells are systematically studied. For this, thin gold nanomeshes with hexagonally ordered holes and periodicities (P) ranging from 202 nm to 2560 nm are prepared by colloidal lithography. In combination with two different active layer materials (P3HT:PC 61 BM and PTB7:PC 71 BM), the optical properties are correlated with the power conversion efficiency (PCE) of the solar cells. A cavity mode is identified at the absorption edge of the active layer material. The resonance wavelength of this cavity mode is hardly defined by the nanomesh periodicity but rather by the absorption of the photoactive layer. This constitutes a fundamental dilemma when using nanomeshes as ITO replacement. The highest plasmonic enhancement requires small periodicities. This is accompanied by an overall low transmittance and high parasitic absorption losses. Consequently, larger periodicities with a less efficient cavity mode, yet lower absorptive losses were found to yield the highest PCE. Nevertheless, ITO-free solar cells reaching ∼77% PCE compared to ITO reference devices are fabricated. Concomitantly, the benefits and drawbacks of this transparent nanomesh electrode are identified, which is of high relevance for future ITO replacement strategies.
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    In-situ terahertz optical Hall effect measurements of ambient effects on free charge carrier properties of epitaxial graphene
    (London : Nature Publishing Group, 2017) Knight, Sean; Hofmann, Tino; Bouhafs, Chamseddine; Armakavicius, Nerijus; Kühne, Philipp; Stanishev, Vallery; Ivanov, Ivan G.; Yakimova, Rositsa; Wimer, Shawn; Schubert, Mathias; Darakchieva, Vanya
    Unraveling the doping-related charge carrier scattering mechanisms in two-dimensional materials such as graphene is vital for limiting parasitic electrical conductivity losses in future electronic applications. While electric field doping is well understood, assessment of mobility and density as a function of chemical doping remained a challenge thus far. In this work, we investigate the effects of cyclically exposing epitaxial graphene to controlled inert gases and ambient humidity conditions, while measuring the Lorentz force-induced birefringence in graphene at Terahertz frequencies in magnetic fields. This technique, previously identified as the optical analogue of the electrical Hall effect, permits here measurement of charge carrier type, density, and mobility in epitaxial graphene on silicon-face silicon carbide. We observe a distinct, nearly linear relationship between mobility and electron charge density, similar to field-effect induced changes measured in electrical Hall bar devices previously. The observed doping process is completely reversible and independent of the type of inert gas exposure.
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    Limbal stromal cells derived from porcine tissue demonstrate mesenchymal characteristics in vitro
    (London : Nature Publishing Group, 2017) Fernández-Pérez, Julia; Binner, Marcus; Werner, Carsten; Bray, Laura J.
    Limbal stromal cells (LSCs) from the human ocular surface display mesenchymal stromal cell characteristics in vitro. In this study, we isolated cells from the porcine limbal stroma (pLSCs), characterised them, and evaluated their ability to support angiogenesis and the culture of porcine limbal epithelial stem cells (pLESCs). The isolated cells adhered to plastic and grew in monolayers in vitro using serum-supplemented or serum-free medium. The pLSCs demonstrated expression of CD29, and cross-reactivity with anti-human CD45, CD90, CD105, CD146, and HLA-ABC. However, expression of CD105, CD146 and HLA-ABC reduced when cultured in serum-free medium. PLSCs did not undergo adipogenic or osteogenic differentiation, but differentiated towards the chondrogenic lineage. Isolated cells were also co-cultured with human umbilical vein endothelial cells (HUVECs) in star-shaped Poly(ethylene glycol) (starPEG)-heparin hydrogels to assess their pericyte capacity which supported angiogenesis networks of HUVECs. PLSCs supported the three dimensional HUVEC network for 7 days. The isolated cells were further growth-arrested and evaluated as feeder cells for pLESC expansion on silk fibroin membranes, as a potential carrier material for transplantation. PLSCs supported the growth of pLESCs comparably to murine 3T3 cells. In conclusion, although pLSCs were not completely comparable to their human counterpart, they display several mesenchymal-like characteristics in vitro.