Kristina Kähm - Bachelor of Science
Kristina Kähm successfully completed her bachelor thesis entitled “Analyse von Glykosaminoglykanen und Fibronektinen in der extrazellulären Matrix zum Nachweis der erfolgten Dezellularisierung von Rattenleber-Explantaten“ and is now a Bachelor of science.
Her project was supervised in cooperation with Prof. Dr. Marcus Frohme, Division Molecular Biotechnology and Functional Genomics, Technical University of Applied Sciences in Wildau, Germany.
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Dr. med. Carolin M. Langer
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Today, Carolin Langer successfully defended her thesis entitled Evaluierung eines Silizium-basierten Eisenoxidpartikels als intrazelluläres Magnetresonanzkontrastmittel für die Leberzelltransplantation „magna cum laude“.

Cellular therapies require methods for noninvasive visualization of transplanted cells. Micron-sized iron oxide particles (MPIOs) generate a strong contrast in magnetic resonance imaging (MRI) and are therefore ideally suited as an intracellular contrast agent to image cells under clinical conditions. However, MPIOs were previously not applicable for clinical use. her thesis focussed on the development and evaluation of silica-based micron-sized iron oxide particles (sMPIOs) with a functionalizable particle surface. Labeling was stable and had no adverse effects on labeled cells. Silica is a biocompatible material that has been approved for clinical use. sMPIOs could therefore be suitable for future clinical applications in cellular MRI, especially in settings that require strong cellular contrast. Moreover, the particle surface provides the opportunity to create multifunctional particles for targeted delivery and diagnostics.

Congratulations !
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Decellularization and oscillating pressure conditions
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The Journal of Tissue Engineering and Regenerative Medicine accepted our latest paper on „Improved rat liver decellularization by arterial perfusion under oscillating pressure conditions“ for publication. Authors are B. Struecker, A. Butter, K. Hillebrandt, D. Polenz , A. Reutzel-Selke, P. Tang, S. Lippert, A. Leder, S. Rohn, D. Geisel, T. Denecke, K. Aliyev, K. Jöhrens, N. Raschzok, P. Neuhaus, J. Pratschke and I.M. Sauer.

One approach of regenerative medicine to generate functional hepatic tissue in vitro is de- and recellularization and several protocols for the decellularization of different species have been published. To the best of our knowledge this is the first report on rat liver decellularization by perfusion via the hepatic artery under oscillating pressure conditions, intending to optimize microperfusion and minimize damage to the ECM. Four decellularization protocols were compared: perfusion via the portal vein (PV) or the hepatic artery (HA), with (+P) or without (-P) oscillating pressure conditions. All rat livers (n=24) were perfused with 1% Triton X-100 and 1% SDS, each for 90 minutes with a perfusion rate of 5ml/min. Perfusion decellularization was observed macroscopically and the decellularized liver matrices (DLMs) were analyzed by histology and biochemical analyses (e.g., levels of DNA, glycosaminoglycans (GAG), and hepatocyte growth factor (HGF). Livers decellularized via the hepatic artery and under oscillating pressure showed a more homogenous decellularization and less remaining DNA, compared to livers of the other experimental groups. The novel decellularization method described is effective, quick (3 hours) and gentle to the ECM and thus represents an improvement of existing methodology.
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Nature Reviews Gastroenterology and Hepatology
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Nature Reviews Gastroenterology and Hepatology invited us to provide a review on liver support strategies.

The treatment of end-stage liver disease and acute liver failure remains a clinically relevant issue. Although orthotopic liver transplantation is a well-established procedure, whole-organ transplantation is invasive and increasingly limited by the unavailability of suitable donor organs. Artificial and bioartificial liver support systems have been developed to provide an alternative to whole organ transplantation, but despite three decades of scientific efforts, the results are still not convincing with respect to clinical outcome. In this Review, conceptual limitations of clinically available liver support therapy systems are discussed. Furthermore, alternative concepts, such as hepatocyte transplantation, and cutting-edge developments in the field of liver support strategies, including the repopulation of decellularized organs and the biofabrication of entirely new organs by printing techniques or induced organogenesis are analysed with respect to clinical relevance. Whereas hepatocyte transplantation shows promising clinical results, at least for the temporary treatment of inborn metabolic diseases, so far data regarding implantation of engineered hepatic tissue have only emerged from preclinical experiments. However, the evolving techniques presented here raise hope for bioengineered liver support therapies in the future.


Update: The review „Liver support strategies: cutting-edge technologies“ (authors: Benjamin Struecker, Nathanael Raschzok & Igor M. Sauer) is now available.
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41st Annual Congress of the ESAO in Rome
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Prof. Celestino Pio Lombardi, Gemelli Polyclinics, Catholic University of the Sacred Heart in Rome, and Prof. Gerardo Catapano organize the 41st Annual Congress of the European Society for Artificial Organs (ESAO) in Rome, Italy.

The 41st ESAO Congress will be focused on “Patient happiness: the Holy Grail of organ substitution”, and will be held on September 17-20, 2014 at the Giovanni XXIII congress center located inside the Gemelli Polyclinics in Rome, Italy. The meeting is expected to attract aprox. 600 participants with both clinical and technical expertise from all over the world.
The objective of the Congress is to bring together scientists with different backgrounds working at the development, optimization and translation to the clinics of treatments of organ deficits based on the use of artificial, bioartificial, and cell-based organs or prostheses, and to discuss the importance of technical, psychological and ethical issues to the happiness of patients with serious tissue or organ deficits so as to re-define the design criteria of devices and treatments.
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12th Congress of the Cell Transplant Society
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The 12th Congress of the Cell Transplant Society tookplace in Milan, Italy, from July 7 to 11, 2013.
Nathanael Raschzok gave a presentation on "Loco-regional detection and stimulation of transplanted liver cells by particle-based miRNA depletion" and Martina Mogl on "isolation of adult hepatocytes and progenitor cells from explanted diseased human livers“.
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IEEE Engineering in Medicine and Biology Society
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The 35th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC’13) will take place 3-7 July 2013, at the Osaka International Convention Center, in Osaka, Japan.
The conference will cover diverse topics such as biomedical engineering, healthcare technologies, and medical and clinical applications.
The ESAO will be represented via a minisymposium entitled "Artificial Organs for Metabolic Support. The most Challenging Problems". Jan Wojcicki will give a presentation on "Artificial Organs for Metabolic Support: The Most Challenging Problems of Artificial Pancreas", Bernd Stegmayr on "Artificial Organs for Metabolic Support: The Most Challenging Problems in Severe Kidney Injury When Dialysis Is Necessary" and Igor Sauer on "Artificial Organs for Metabolic Support: The Most Challenging Problems of Liver Support".
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Noninvasive monitoring of liver cell transplantation
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Our latest review on „Noninvasive monitoring of liver cell transplantation“ (authors are N. Raschzok, H.M. Morgül, L. Stelter & I.M. Sauer) is available in Imaging in Medicine, 2013; 5: 47-61:
Liver cell transplantation was developed as a therapeutic alternative to solid liver transplantation in the management of liver-based metabolic disorders and may be useful for the treatment of acute or chronic liver failure. While clinical studies have demonstrated temporal amelioration of the symptoms of metabolic liver disorders by transplanted liver cells, the long-term outcome of liver cell transplantation is still insufficient. A major limitation for improving liver cell transplantation is the inability to track the fate of cells once they have been infused. Radionuclide-based imaging, MRI and optical methods have been investigated as methods for noninvasive monitoring of liver cell transplantation. This article summarizes and critically discusses these approaches, with a special focus on MRI-based tracking of transplanted liver cells and provides an outlook on possible clinical applications for the near future.
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Einladunfgzur öffentlichen Abschlusspräsentation
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Sehr geehrte Damen und Herren,
Dear ladies and gentlemen,

Sie sind herzlich eingeladen, unserer öffentlichen Abschlusspräsentation unseres EU/EFRE-Projekts am 20.03.2013 um 15:00 Uhr beizuwohnen. Zusammen mit unseren Partnern der Firma microparticles GmbH werden wir den aktuellen Stand zur „Entwicklung von Partikel zur Detektion und ultralokoregionären Stimulation transplantierter Leberzellen“ darlegen.
You are cordially invited to attend our public presentation of our EU/EFRE project. Together with our partners of microparticles GmbH we will present our latest results concerning the „Development of particles for detection and ultralocoregional stimulation of transplanted liver cells“.

Wann/When?
20.03.2013 um/at 15:00

Wo/Where?
Experimentelle Chirurgie und Regenerative Medizin
Klinik für Allgemein-, Viszeral- und Transplantationschirurgie
Charité, Campus Virchow-Klinikum
Forschungshaus/BMFZ
Pilzraum, 1.OG

Wir wären dankbar, wenn Sie Ihr Kommen via email (anja.selke@charite.de)bestätigen könnten.
RSVP via email (anja.selke@charite.de).
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Dr. Nils Bilecke
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Today, Nils Billecke successfully defended his doctoral thesis magna cum laude. The title of his presentation was „Bioreaktorsystem zur videomikroskopischen Langzeituntersuchung von Zellen in Mono- und Kokultur“.

Congratulations!
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GASL Poster Prize
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Nathanael Raschzok's poster entitled "Serum protein biomarkers for acute rejection
in liver transplantation" was awarded with the GASL 2013 poster prize during the 29th Annual Meeting of the German Association for the Study of the Liver (GASL) in Hannover, Germany. Co-authors are Kukuh A. Prabowo, Anja Reutzel-Selke, Rosa B. Schmuck, Mehmet H. Morgul, Laura M. Tannus, Stephanie König, Sven Jonas, Peter Neuhaus, and Igor M. Sauer.


Although 20–40% of patients experience at least one episode of acute rejection (AR) after liver transplantation (LTx), diagnosis of AR is still mainly based on tissue analysis from liver biopsies. Biomarker routinely taken from blood samples would be a powerful non-invasive tool for monitoring of the liver graft status. The aim of this study was to investigate the diagnostic and prognostic value of serum protein biomarkers for acute rejection in LTx recipients. Serum samples from n=20 patients with AR and n=15 stable controls were analyzed. CXCL9 and CD31 were up-regulated in AR samples compared to controls at the time point of histologically proven rejection and at earlier time points prior rejection. Areas under the Receiver Operation Characteristics (ROC) curves were 0.6 and 0.7 at the day of rejection and 0.8 at POD1 for CXCL9 and CD31, respectively. IL-6 was increased prior and during rejection, while CD44 showed an opposite trend.
Serum protein biomarkers could be valuable for detection and prediction of AR after LTx. However, a larger number of patients, additional control groups, and prospective clinical trials will be necessary to proof the clinical utility of this diagnostic tool.

Moreover, Rosa Schmuck presented her data on "Bile: miRNA pattern and cell morphology as a diagnostic tool after liver transplantation" (co-authors: Nathanael Raschzok, Anja Reutzel-Selke, Steffen Lippert, Stephanie König, Kukuh A. Prabowo, Mehmet H. Morgul, Laura M. Tannus, Sven Jonas, Peter Neuhaus, and Igor M. Sauer) and Luisa Lisboa her work on "MicroRNA miR-352 in early liver regeneration: what role?" (co-authors: Nathanael Raschzok, Annekatrin Leder, Natalie Schlüter, Marc Jörres, Susanne Kolano, Antje Butter, Steffen Lippert, Wiebke Werner, Peter Neuhaus, and Igor M. Sauer).
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David Mücke successfully defended thesis
Today, David Mücke successfully defended his thesis magna cum laude with respect to his work on the in vitro evaluation of MRI contrast agents for detection of primary human hepatocytes („In vitro Evaluierung von Magnetresonanztomografie-Kontrastmitteln für die Markierung primärer humaner Hepatozyten“).

Congratulations !
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XXXX ESAO Congress in Glasgow
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The European Society for Artificial Organs (ESAO) invites you to the XXXX ESAO Congress of the society to be held in Glasgow (Scotland, UK), September 11th-14th 2013.The motto of the ESAO congress will be 'lab to patient - from concept to treatment.
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Presentations at EASO 2012 in Rostock, Germany
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This year members of the team gave the following presentations:

“Liver: Current regenerative strategies and future solutions for the liver" (N. Raschzok, oral presentation)
"Neohybrid liver graft - a novel concept of in vivo tissue-engineering" (S. Rohn, oral presentation)
"Micro RNAs in liver regeneration: the mysterious MIR-352" (L. Lisboa, oral presentation)
"Micron-sized iron oxide particles for detection and loco-regional stimulation of transplanted liver cells" (A. Leder, oral presentation)
"Prospective validation of cross organ serum protein biomarkers – Initial results with CXCL9 and CD44 for diagnosis of acute liver rejection" (K.A. Prabowo, poster presentation)
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MRI and ectopic liver cell transplantation - new paper
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Nathanael Raschzok’s latest paper on „Feasibility of fast dynamic MRI for noninvasive monitoring during ectopic liver cell transplantation to the spleen in a porcine model“ is now available in AJR Am J Roentgenol. 2012 Jun;198(6):1417-23.
Liver cell transplantation is a promising approach for the treatment of metabolic liver disorders. However, a method for noninvasive monitoring during liver cell transplantation is not available clinically. The aim of this study was to investigate the feasibility of fast dynamic MRI monitoring during liver cell infusion to the spleen, which is considered an ectopic implantation site for liver cell transplantation. Porcine liver cells were labeled with micron-sized iron oxide particles and infused to the spleens of pigs (n = 5) via the lineal artery. MRI was performed using a 3-T MR scanner. Initially, T1- and T2-weighted pulse sequences were tested. Thereafter, fast dynamic MRI was performed during cell infusion. MR findings were verified by immunohistological examinations.

Images from static MRI (TR/TE, 2500/105.2) showed significantly lower signal intensity and signal-to-noise ratio after cell infusion compared with pretransplant images. T2-weighted fast dynamic MRI enabled visualization of signal decrease of the spleen during cell infusion. When cells were infused systemically, no signal changes in the spleen were observed. This study shows that fast dynamic MRI can enable noninvasive monitoring during liver cell transplantation to the spleen. This approach could be useful for preclinical studies and for quality control of clinical liver cell transplantation.
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ESAO 2012 - Final Program Online!

Prof. Dr. Gustav Steinhoff, congress president of the XXXIX. ESAO Congress, invites you to Rostock on September 26th – 29th, 2012. The venue of the ESAO 2012 congress is the Academy of Music and Theatre, which resides in an old monastery in the city centre.
The motto of the ESAO Congress 2012 will be “from replacement to regeneration – from science to clinic”. The current state of organ assist and organ support allows for a rapidly advancing clinical practice for several hundred thousand patients worldwide.
The scientific program committee did select 59 keynote lectures of renowned international experts, 131 selected oral presentations and 101 poster presentations from worldwide scientific contributors. Nine poster presentations were selected for short oral presentation. We provide a clear program structure by highlighting one special organ system each congress day: heart/cardiovascular (Chair: G. Steinhoff) , liver (Chair: S. Mitzner) and kidney (Chair: W. Ramlow). The program comprises 45 oral and 2 poster sessions with cardiovascular, dialysis, biomaterials and apheresis topics (www.esao2012.org). Above all the congress program integrates aspects of both basic science and clinical development with a clear focus on translation and clinical practice. We intend to host you on an excellent and exciting congress by inviting outstanding experts and by giving young and promising clinicians and scientists the opportunity to present their work. Especially for young scientists there will be one day for yESAO activities (Tuesday, Sept. 25, 2012). Industry symposia, a poster exhibition and an industrial exhibition will complete the congress program.

We are looking forward to seeing you in Rostock 2012.

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XXXIX ESAO Congress in Rostock, Germany
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On behalf of the European Society for Artificial Organs (ESAO), Prof. Dr. med. Gustav Steinhoff invites you to the XXXIX. ESAO Congress to be held in Rostock (Germany), September 26th – 29th, 2012. Rostock is a prospering and easy-to-reach hanseatic city directly located at the Baltic Sea coast. The venue of the ESAO 2012 congress is the Academy of Music and Theatre, which resides in an old monastery in the city centre. Rostock is home to one of the oldest universities in the world: founded in 1419. The motto of the ESAO Congress 2012 will be “from replacement to regeneration – from science to clinic”. The meeting will provide a clear program structure by highlighting one special organ system each congress day: heart/cardiovascular, liver and kidney. Above all the congress program integrates aspects of both basic science and clinical development with a clear focus on translation and clinical practice. We intend to prepare an excellent and exciting congress by inviting outstanding experts and by giving young and promising clinicians and scientists the opportunity to present their work. Especially for young scientists there will be one day for yESAO activities. Industry symposia, a poster exhibition and an industrial exhibition will complete the congress program.
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CARS microscopy of MPIO
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Following a successful project sponsored by the BMBF G. Pless, I.M. Sauer and U. Rauen report on the "Improvement of the cold storage of isolated human hepatocytes" (Cell Transplant. 2011 Jun 7. [Epub ahead of print]).
Increasing amounts of human hepatocytes are needed for clinical applications and different fields of research, such as cell transplantation, bioartificial liver support and pharmacological testing. This demand calls for adequate storage options for isolated human liver cells. As cryopreservation results in severe cryoinjury, short term storage is currently performed at 2-8º C in preservation solutions developed for the storage of solid organs. However, besides slowing down cell metabolism, cold also induces cell injury, which is, in many cell types, iron-dependent and not counteracted by current storage solutions. In this study, we aimed to characterize storage injury to human hepatocytes and develop a customized solution for cold storage of these cells. Human hepatocytes were isolated from material obtained from partial liver resections, seeded in monolayer cultures and, after a pre-culture period, stored in the cold in classical and new solutions followed by rewarming in cell culture medium.Human hepatocytes displayed cold-induced injury, resulting in > 80% cell death (LDH release) after one week of cold storage in University of Wisconsin solution or cell culture medium and 3 h of rewarming. Cold-induced injury could be significantly reduced by the addition of the iron chelators deferoxamine and LK 614. Experiments with modified solutions based on the new organ preservation solution Custodiol-N showed that ion-rich variants were better than ion-poor variants, chloride-rich solutions better than chloride-poor solutions, potassium as main cation superior to sodium and pH 7.0 superior to pH 7.4. LDH release after two weeks of cold storage in the thus optimized solution was below 20%, greatly improving cold storage of human hepatocytes. The results were confirmed by the assessment of hepatocellular mitochondrial membrane potential and functional parameters (resazurin reduction, glucacon-stimulated glucose liberation) and thus suggest the use of a customized hepatocyte storage solution for the cold storage of these cells.
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Fast dynamic MRI during liver cell Tx
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Micrometer-sized iron oxide particles (MPIOs) attract increasing interest as contrast agents for cellular tracking by clinical Magnetic Resonance Imaging (MRI). Despite the great potential of MPIOs for in vivo imaging of labeled cells, little is known on the intracellular localization of these particles following uptake due to the lack of techniques with the ability to monitor the particle uptake in vivo at single-cell level. Here, we show that coherent anti-Stokes Raman scattering (CARS) microscopy enables non-invasive, label-free imaging of MPIOs in living cells with sub-micron resolution in three dimensions. CARS allows simultaneous visualization of the cell framework and the MPIOs, where the particles can be readily distinguished from other cellular components of comparable dimensions, and localized inside the cell.
The fruitful cooperation with the FOM Institute AMOLF in Masterdam resulted in the paper "CARS microscopy for the visualization of micrometer-sized iron oxide MRI contrast agents in living cells" (Rago G, Langer CM, Brackman C, Day JP, Domke KF, Raschzok N, Schmidt C, Sauer IM, Enejder A, Mogl MT, Bonn M.) published in Biomed Opt Express. 2011 Sep 1;2(9):2470-83.
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Improved cold storage of human hepatocytes
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As a first result of our latest projects concerning the role of miRNA in liver regeneration the American Journal of Physiology - Regulatory, Integrative and Comparative Physiology has accepted our paper "Temporal expression profiles indicate a primary function for microRNA during the peak of DNA replication after rat partial hepatectomy": The liver has the unique capacity to regenerate after surgical resection. However, the regulation of liver regeneration is not completely understood. Recent reports indicate an essential role for small non-coding microRNAs (miRNAs) in the regulation of hepatic development, carcinogenesis, and early regeneration. We hypothesized that miRNAs are critically involved in all phases of liver regeneration after partial hepatectomy. We performed miRNA microarray analyses after 70% partial hepatectomy in rats under isoflurane anesthesia at different time points (0 hours - 5 days) and after sham laparotomy. Putative targets of differentially expressed miRNAs were determined using a bioinformatic approach. 2D-PAGE proteomic analyses and protein identification were performed on specimens at 0 and 24 hours after resection. The temporal dynamics of liver regeneration were characterized by BrdU, PCNA, IL-6, and HGF. We demonstrate that miRNA expression patterns changed during liver regeneration and that these changes were most evident during the peak of DNA replication at 24 hours after resection. Expression of thirteen miRNAs was significantly reduced 12-48 hours after resection (> 25% change), ouf of which downreguation was confirmed in isolated hepatocytes for 6 miRNAs at 24 hours, whereas three miRNAs were significantly upregulated. Proteomic analysis revealed 65 upregulated proteins; among them 23 represent putative targets of the differentially expressed miRNAs. We provide a temporal miRNA expression and proteomic dataset of the regenerating rat liver, which indicates a primary function for miRNA during the peak of DNA replication. These data will assist further functional studies on the role of miRNAs during liver regeneration. Authors are N. Raschzok, W. Werner, H. Sallmon, N. Billecke, C. Dame, P. Neuhaus and I.M. Sauer.
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Monitoring cell transplantation in swine model via MRI

Nora Kammer's paper in Artificial Organs on "Labelling of primary human hepatocytes with micron-sized iron oxide particles in suspension culture suitable for large-scale preparation" is available pre-print. Co-authors are Nils Billecke, Mehmet H. Morgul, Michaela K. Adonopoulou, Martina Mogl, Mao D. Huang, Stefan Florek, Katharina R. L. Schmitt, Nathanael Raschzok and Igor M. Sauer.

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SlideReactor starlet at exhibition
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A multicompartment SlideReactor is shown at the exhibition “WeltWissen – World Knowledge”.

This year, Berlin celebrates 200 years of the Humboldt University, 300 years of the Charité, 300 years since the first statute and first publication by the Academy of the Sciences and, one year later, 100 years of the Max Planck and Kaiser Wilhelm Society and the 350th birthday of the Berlin State Library. The exhibition “WeltWissen – World Knowledge” is the high point of the Berlin Year of Science. The Humboldt University, the Charité, the Berlin-Brandenburg Academy of the Sciences and Humanities and the Max Planck Society have organised the exhibition as a unique joint project. The Technical University, the Berlin State Museums and the Deutsches Museum, Munich are involved as partners. From 24 September 2010 to 9 January 2011, Martin-Gropius-Bau will be host ing its “WeltWissen“ (World Knowledge) exhibition which takes a look at 300 years of the science in Berlin from an all-embracing perspective that crosses institutions, disciplines and epochs. The exhibition is the high point of the Berlin Year of Science. On an exhibition space of more than 3,200 square metres, visitors are presented with over 1,500 original exhibits, installations and media stations. The Humboldt University, the Charité, the Berlin-Brandenburg Academy of the Sciences and Humanities and the Max Planck Society have organised the exhibition as a unique joint project.
The exhibition correlates sciences in Berlin to the world: only the dynamic interplay of local imprinting and worldwide networking has allowed Berlin since 300 years to generate knowledge and share it with the world. Concrete and highly vivid stories and biographies of objects, researchers and institutions offer exciting insights into the scientific environment. “WeltWissen – World Knowledge” shows how scientists in Berlin work, how they network internationally, how they break down the boundaries of their departments and how they transformed Berlin into a scientific metropolis.

WeltWissen. 300 Years of Science in Berlin 24 September 2010 – 9 January 2011 Martin-Gropius-Bau, Niederkirchnerstrasse 7, 10963 Berlin
Opening times: Wed - Mo: 10.00 am – 8.00 pm, closed on Tuesdays
Admission: 6 €, reduced 4€ . Free admission for children and adolescents up to an including 16 years of age, two escorts each per kindergarten group or school class as well as recipients of unemployment benefit level II
Public transport: Underground line 2 (Potsdamer Platz), city train lines 1, 2, 25 (Potsdamer Platz or Anhalter Bahnhof), Buses: M29 (Anhalter Bahnhof) / M41 (Abgeordnetenhaus) Please find more information at: www.weltwissen-berlin.de, www.gropiusbau.de

Copyright of picture: Roman März

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