Ludwig Boltzmann Institute for Clinical and Experimental Traumatology

Vienna, Austria

Ludwig Boltzmann Institute for Clinical and Experimental Traumatology

Vienna, Austria

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Geppert M.,University of Bremen | Geppert M.,Center for Environmental Research and Sustainable Technology | Hohnholt M.C.,University of Bremen | Hohnholt M.C.,Center for Environmental Research and Sustainable Technology | And 8 more authors.
Nanotechnology | Year: 2011

Magnetic iron oxide nanoparticles (Fe-NP) are currently considered for various diagnostic and therapeutic applications in the brain. However, little is known on the accumulation and biocompatibility of such particles in brain cells. We have synthesized and characterized dimercaptosuccinic acid (DMSA) coated Fe-NP and have investigated their uptake by cultured brain astrocytes. DMSA-coated Fe-NP that were dispersed in physiological medium had an average hydrodynamic diameter of about 60nm. Incubation of cultured astrocytes with these Fe-NP caused a time-and concentration-dependent accumulation of cellular iron, but did not lead within 6h to any cell toxicity. After 4h of incubation with 100-4000 νM iron supplied as Fe-NP, the cellular iron content reached levels between 200 and 2000 nmolmg-1 protein. The cellular iron content after exposure of astrocytes to Fe-NP at 4 °C was drastically lowered compared to cells that had been incubated at 37 °C. Electron microscopy revealed the presence of Fe-NP-containing vesicles in cells that were incubated with Fe-NP at 37 °C, but not in cells exposed to the nanoparticles at 4 °C. These data demonstrate that cultured astrocytes efficiently take up DMSA-coated Fe-NP in a process that appears to be saturable and strongly depends on the incubation temperature. © 2011 IOP Publishing Ltd.


Geppert M.,University of Bremen | Hohnholt M.C.,University of Bremen | Nurnberger S.,Medical University of Vienna | Nurnberger S.,Ludwig Boltzmann Institute for Clinical and Experimental Traumatology | Dringen R.,University of Bremen
Acta Biomaterialia | Year: 2012

To investigate the cellular consequences of a prolonged cellular presence of large amounts of iron oxide nanoparticles (IONPs) as well as the fate of such particles in brain cells, cultured primary astrocytes were loaded for 4 h with dimercaptosuccinate-coated IONPs. Subsequently, the IONP-treated cells were incubated for up to 7 days in IONP-free medium and the cell viability, metabolic parameters and iron metabolism of the cells were investigated. Despite an up to 100-fold elevated specific cellular iron content, IONP-loaded cells remained viable throughout the 7 day main incubation and did not show any substantial alteration in glucose and glutathione metabolism. During the incubation, the high cellular iron content of IONP-loaded astrocytes remained almost constant. Electron microscopy revealed that after 7 days of incubation most of the cellular iron was still present in IONP-filled vesicles. However, the transient appearance of reactive oxygen species (ROS) as well as a strong increase in cellular levels of the iron storage protein ferritin suggest that at least some low-molecular-weight iron was liberated from the accumulated IONPs. These results demonstrate that even the prolonged presence of large amounts of accumulated IONPs does not harm astrocytes and that these cells store IONP-derived iron in ferritin. © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.


Esteban M.A.,South China Institute for Stem Cell Biology and Regenerative Medicine | Wang T.,South China Institute for Stem Cell Biology and Regenerative Medicine | Qin B.,South China Institute for Stem Cell Biology and Regenerative Medicine | Yang J.,South China Institute for Stem Cell Biology and Regenerative Medicine | And 22 more authors.
Cell Stem Cell | Year: 2010

Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) by defined factors. However, the low efficiency and slow kinetics of the reprogramming process have hampered progress with this technology. Here we report that a natural compound, vitamin C (Vc), enhances iPSC generation from both mouse and human somatic cells. Vc acts at least in part by alleviating cell senescence, a recently identified roadblock for reprogramming. In addition, Vc accelerates gene expression changes and promotes the transition of pre-iPSC colonies to a fully reprogrammed state. Our results therefore highlight a straightforward method for improving the speed and efficiency of iPSC generation and provide additional insights into the mechanistic basis of the reprogramming process. © 2010 Elsevier Inc. All rights reserved.


Trattnig S.,Medical University of Vienna | Trattnig S.,Ludwig Boltzmann Institute for Clinical and Experimental Traumatology | Stelzeneder D.,Medical University of Vienna | Goed S.,Medical University of Vienna | And 8 more authors.
European Radiology | Year: 2010

Objective: To assess the relationship of morphologically defined lumbar disc abnormalities with quantitative T2 mapping. Methods: Fifty-three patients, mean age 39 years, with low back pain were examined by MRI at 3 T (sagittal T1-fast spin echo (FSE), three-plane T2-FSE for morphological MRI, multi-echo spin echo for T2 mapping). All discs were classified morphologically. Regions of interest (ROIs) for the annulus were drawn. The space in between was defined as the nucleus pulposus (NP). To evaluate differences between the classified groups, univariate ANOVA with post hoc Games-Howell and paired two-tailed t tests were used. Results: In 265 discs we found 39 focal herniations, 10 annular tears, 123 bulging discs and 103 "normal discs". T2 values of the NP between discs with annular tear and all other groups were statistically significantly different (all p≥0.01). Discs with annular tears showed markedly lower NP T2 values than discs without. The difference in NP T2 values between discs with focal herniation and normal discs (p=0.005) was statistically significant. There was no difference in NP T2 values between bulging and herniated discs (p=0.11) Conclusion: Quantitative T2 mapping of the nucleus pulposus of the intervertebral disc in the lumbar spine at 3 T reveals significant differences in discs with herniation and annular tears compared with discs without these abnormalities. © 2010 European Society of Radiology.


Malandrino A.,Institute of Bioengineering of Catalonia IBEC | Fritsch A.,Vienna University of Technology | Lahayne O.,Vienna University of Technology | Kropik K.,Ludwig Boltzmann Institute for Clinical and Experimental Traumatology | And 4 more authors.
Materials Letters | Year: 2012

The extremely fine structure of vertebral cortex challenges reliable determination of the tissue's anisotropic elasticity, which is important for the spine's load carrying patterns often causing pain in patients. As a potential remedy, we here propose a combined experimental (ultrasonic) and modeling (micromechanics) approach. Longitudinal acoustic waves are sent in longitudinal (superior-inferior, axial) as well as transverse (circumferential) direction through millimeter-sized samples containing this vertebral cortex, and corresponding wave velocities agree very well with recently identified 'universal' compositional and acoustic characteristics (J Theor Biol 287:115, 2011), which are valid for a large data base comprising different bones from different species and different organs. This provides evidence that the 'universal' organization patterns inherent to all the bone tissues of the aforementioned data base also hold for vertebral bone. Consequently, an experimentally validated model covering the mechanical effects of this organization patterns (J Theor Biol 244:597, 2007, J Theor Biol 260:230, 2009) gives access to the complete elasticity tensor of human lumbar vertebral bone tissue, as a valuable input for structural analyses aiming at patient-specific fracture risk assessment, e.g. based on the Finite Element Method. © 2012 Elsevier B.V. All rights reserved.


Zhou T.,Chinese Academy of Sciences | Benda C.,Chinese Academy of Sciences | Benda C.,University of Natural Resources and Life Sciences, Vienna | Duzinger S.,University of Natural Resources and Life Sciences, Vienna | And 21 more authors.
Journal of the American Society of Nephrology | Year: 2011

Forced expression of selected transcription factors can transform somatic cells into embryonic stem cell (ESC)-like cells, termed induced pluripotent stem cells (iPSCs). There is no consensus regarding the preferred tissue from which to harvest donor cells for reprogramming into iPSCs, and some donor cell types may be more prone than others to accumulation of epigenetic imprints and somatic cell mutations. Here, we present a simple, reproducible, noninvasive method for generating human iPSCs from renal tubular cells present in urine. This procedure eliminates many problems associated with other protocols, and the resulting iPSCs display an excellent ability to differentiate. These data suggest that urine may be a preferred source for generating iPSCs. Copyright © 2011 by the American Society of Nephrology.


Weilner S.,University of Natural Resources and Life Sciences, Vienna | Weilner S.,Ludwig Boltzmann Institute for Clinical and Experimental Traumatology | Schraml E.,University of Natural Resources and Life Sciences, Vienna | Redl H.,Ludwig Boltzmann Institute for Clinical and Experimental Traumatology | And 4 more authors.
Experimental Gerontology | Year: 2013

Changes of factors circulating in the systemic environment during human aging have been investigated for a long time. Only recently however, miRNAs have been found to be secreted into the systemic and tissue environments where they are protected from RNAses by either carrier proteins or by being packaged into microvesicles. These miRNAs are then taken up by recipient cells, changing the cellular behavior by the classical miRNA induced silencing of target mRNAs. The origin of circulating miRNAs, however, is in most instances unclear, but senescent cells emerge as a possible source of such secreted miRNAs. Since differences in the circulating miRNAs have been found in a variety of age-associated diseases, and accumulation of senescent cells in the elderly emerges as a possible detrimental factor in aging, it is well conceivable that these miRNAs might contribute to the functional decline observed during aging of organisms.Therefore, we here give an overview on current knowledge on microvesicular secretion of miRNAs, changes of the systemic and tissue environments during aging of cells and organisms. Finally, we summarize current knowledge on miRNAs that are found to be specific for age-associated diseases. © 2012 Elsevier Inc.


Cai J.,Chinese Academy of Sciences | Li W.,Chinese Academy of Sciences | Su H.,University of Hong Kong | Qin D.,Chinese Academy of Sciences | And 16 more authors.
Journal of Biological Chemistry | Year: 2010

The umbilical cord and placenta are extra-embryonic tissues of particular interest for regenerative medicine. They share an early developmental origin and are a source of vast amounts of cells with multilineage differentiation potential that are poorly immunogenic and without controversy. Moreover, these cells are likely exempt from incorporated mutations when compared with juvenile or adult donor cells such as skin fibroblasts or keratinocytes. Here we report the efficient generation of induced pluripotent stem cells (iPSCs) from mesenchymal cells of the umbilical cord matrix (up to 0.4% of the cells became reprogrammed) and the placental amniotic membrane (up to 0.1%) using exogenous factors and a chemical mixture. iPSCs from these 2 tissues homogeneously showed human embryonic stem cell (hESC)-like characteristics including morphology, positive staining for alkaline phosphatase, normal karyotype, and expression of hESC-like markers including Nanog, Rex1, Oct4, TRA-1-60, TRA-1-80, SSEA-3, and SSEA-4. Selected clones also formed embryonic bodies and teratomas containing derivatives of the 3 germ layers, and could as well be readily differentiated into functional motor neurons. Among other things, our cell lines may prove useful for comparisons between iPSCs derived from multiple tissues regarding the extent of the epigenetic reprogramming, differentiation ability, stability of the resulting lineages, and the risk of associated abnormalities. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.


Bertl K.,Medical University of Vienna | Bertl K.,Malmö University | Hirtler L.,Medical University of Vienna | Dobsak T.,Medical University of Vienna | And 5 more authors.
European Radiology | Year: 2015

Objectives: CT assessment of the entire course of the inferior alveolar artery (IAA) within the mandibular canal.Methods: After contrast medium injection (180 or 400 mg/ml iodine concentration) into the external carotid arteries of 15 fresh human cadaver heads, the main IAA’s position in the canal (cranial, buccal, lingual or caudal) was assessed in dental CT images of partially edentulous mandibles.Results: The course of the main IAA could be followed at both iodine concentrations. The higher concentration gave the expected better contrast, without creating artefacts, and improved visibility of smaller arteries, such as anastomotic sections, dental branches and the incisive branch. The main IAA changed its position in the canal more often than so far known (mean 4.3 times, SD 1.24, range 2–7), but with a similar bilateral course. A cranial position was most often detected (42 %), followed by lingual (36 %), caudal (16 %) and buccal ( 6 %).Conclusions: With this non-invasive radiologic method, the entire course of the main IAA in the mandibular canal could be followed simultaneously with other bone structures on both sides of human cadaver mandibles. This methodology allows one to amend existing anatomical and histological data, which are important for surgical interventions near the mandibular canal.Key points: • Contrast medium injection displayed the inferior alveolar artery’s course on mandibular CTs• An iodine concentration of 400 mg/ml enabled visibility until the chin• Frequent position changes of the artery in the mandibular canal were detected• Cranial and lingual positions were most often determined• Course similarities on the respective left and right sides were found © 2014, European Society of Radiology.


Nuernberger S.,Medical University of Vienna | Nuernberger S.,Ludwig Boltzmann Institute for Clinical and Experimental Traumatology | Cyran N.,University of Vienna | Albrecht C.,Medical University of Vienna | And 3 more authors.
Biomaterials | Year: 2011

Scaffold architecture and composition are important parameters in cartilage tissue engineering. In this in vitro study, we compared the morphology of four different cell-graft systems applied in clinical cartilage regeneration and analyzed the cell distribution (DAPI nuclei staining) and cell-scaffold interaction (SEM, TEM). Our investigations revealed major differences in cell distribution related to scaffold density, pore size and architecture. Material composition influenced the quantity of autogenous matrix used for cellular adhesion. Cell bonding was further influenced by the geometry of the scaffold subunits. On scaffolds with widely spaced fibers and a thickness less than the cell diameter, chondrocytes surrounded the scaffold fibers with cell extensions. On those fibers, chondrocytes were spherical, suggesting a differentiated phenotype. Fiber sizes smaller than chondrocyte size, and widely spaced, are therefore beneficial in terms of improved adhesion by cell shape adaptation. They also support the differentiated stage of chondrocytes by preventing the fibroblast-like and polygonal cell shape, at least briefly. © 2010 Elsevier Ltd.

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