News

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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Biologisierte Medizintechnik
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Die Berlin Partner für Wirtschaft und Technologie, Bereich Medizintechnik, die Charité - Universitätsmedizin Berlin und die IHK Berlin laden zum
28. Treffpunkt Medizintechnik „Biologisierte Medizintechnik“
am Donnerstag, 25. September 2014, 9 bis 17 Uhr
in der Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum
ein.
Mit dem „Treffpunkt Medizintechnik“ wird eine interdisziplinäre Dialogplattform für Klinik, Wissenschaft und Wirtschaft geboten.
Die Deadline für Vortragsmeldungen ist der 11. April 2014. Unter www.healthcapital.de/TP-Med finden Sie weitere Informationen und haben die Möglichkeit, sich auch online anzumelden.
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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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Henriette Riedel successfully defended her thesis
Today, Henriette Riedel successfully defended her thesis entitled Etablierung der kombinierten Transplantation syngener Hepatozyten mit allogenem Lebertransplantat im Rattenmodell zur Untersuchung der Toleranzinduktion „magna cum laude“.

Congratulations !
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ESAO 2013 in Glasgow
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The XXXX ESAO Congress took place in Glasgow, September 11th - 14th, 2013. This year we had three oral presentations focussing on our latest results in decellularization and recellularization of the liver. Ben Strücker presented our latest results on „Improved rat liver decellularization by arterial perfusion under oscillating surrounding pressure“. Antje Butter and Karl Hillebrandt gave two oral presentations during the yESAO Rapid Fire Session on „Proprietary rat liver decellularization device utilizing oscillating surrounding pressure to improve micro perfusion within the organ“ and Pig liver decellularisation through portal vein and hepatic artery perfusion under oscillating surrounding pressure“.
Furthermore, Karl Hillebrandt received the „2. Prize for the best Poster“!
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ESOT 2013 in Vienna
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Martina Mogl gave an oral presentation on „Characterization of cells isolated from explanted diseased human livers and evolution after cold storage“ at this year’s 16th Congress of the European Society for Organ Transplantation (ESOT) in Vienna.
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Functionalizable silica-based MPIO for cellular MRI
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Our latest manuscript entitled "Functionalizable silica-based micron-sized iron oxide particles for cellular Magnetic Resonance Imaging" was accepted for publication in the journal "Cell Transplantation".

Cellular therapies require methods for non-invasive visualization of transplanted cells. Micron-sized iron oxide particles (MPIOs) generate 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. Here, we present the development and evaluation of silica-based micron-sized iron oxide particles
(sMPIOs) with a functionalizable particle surface.


UPDATE: The paper is now available (Cell Transplant. 2013; 22(11): 1959-1570)
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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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R.B.V. Schmuck received Charité Robert-Koch-Prize 2012
Today, Rosa Schmuck received the 2012 Charité Robert-Koch-Prize for her doctoral thesis entitled „Genotypic and phenotypic characterization of side population of gastric cancer cell lines“ (group of Prof. C. Röcken).

The Side Population (SP) of tumor cell lines shares characteristics with tumor stem cells. In this study we phenotypically and genotypically characterized the SP of gastric cancer cell lines. SPs were obtained from MKN45- and AGS-gastric cancer cells using Hoechst 33342 staining and fluorescence-activated cell sorting (FACS). SP cells were subsequently studied morphologically (cytology, immunocytochemistry), on the transcriptional level (gene array) and in cell culture (recultivation assays). Genes differentially expressed in the SP cells were evaluated by immunohistochemistry in tissue from gastric cancer patients. SP cells were smaller and rounder then Non-SP cells. SP cells self-renewed in re-cultivation experiments and differentiated into SP- and Non-SP cells. Re-cultivated SP- and Non-SP cells showed distinct phenotypes in culture regarding cell shape and colony-formation. SP cells had increased levels of the stem cell markers CD133 and Musashi1. Transcriptional analyses demonstrated that SP cells express genes that encode for stem cell properties like FZD7, HEY1, SMO and ADAM17. Finally she found ADAM17 and FZD7 to be differentially expressed in human gastric cancer, with FZD7- positive intestinal type cancers showing a significant shorter patient survival. In conclusion human gastric cancer cell lines enclose a phenotypically and genotypically distinct cell population with tumor stem cell features. Phenotypical characteristics of this distinct cell population are also present in gastric cancer tissue and seem to correlate with patient survival.
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TTS 2012 - Thank you!
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The Science Circuses are located at each end of the Exhibition Area. You will find the Mini-Theatres for the Mini-Oral Sessions here as well as the Poster Lounges and the Web Stations. Science Circus I includes Mini-Theatres 1 – 5; Science Circus II includes Mini-Theatres 6 – 10. In each Science Circus you will find Web Stations where you can access the web as well as the ePosters.
Via wireless headphones and dedicated channels for each mini-theater this is – to our knowledge – the first successful concept for mini-oral presentations!
Thanks to m-events and Interplan for the tremendous support!

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TTS 2012 | Over 500 presentations online!

The LOC would like to thank all participants for a tremendous 24th International Congress of The Transplantation Society in Berlin!
2268 abstracts were submitted and more than 4800 delegates from 94 countries attended the congress!
The Postgraduate Weekend offered 14 workshops with 45 speakers. Beside 29 Sunrise Symposia with 103 Speakers, 34 State of the Art Sessions with 138 speakers and five Plenary Sessions (16 speakers) we had 53 sessions with 465 oral presentations and 37 sessions with 287 mini oral presentations !
Furthermore, we would like to thank Astrid Enke, Lena Dochat and Stefanie Rensch (Interplan) and the technical experts at m-Events for their excellent work !
As Science and Medicine is nothing without vivid life we would like to thank Rotfront, Berlin Comedian Harmonists and the Capital Dance Orchestra for their memorable performances!

All the great photos by Jan Pauls.
The organ sculptures were made by Jan Pareike.

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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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TTS 2012 | Presentations
We had 4 oral presentations and one poster presentation at TTS 2012..
Martina Mogl presented "Neohybrid Liver Graft - a Novel Concept of in Vivo Tissue-Engineering"
Rosa Schmuck presented our first results concerning "miRNA Pattern Within the Bile as a Diagnostic Tool after Liver Transplantation"
Nathanael Raschzok gave an oral presentation entitled "Silica-Based Micron-Sized Iron Oxide Particles for Detection and Loco-Regional Stimulation of Transplanted Liver Cells"
Haluk Morgül gave a talk on "MicroRNA as Biomarker for Diagnosis and Prediction of Recurrence of Human Hepatocellular Carcinoma after Liver Transplantation - Preliminary Results from a Multicenter Database"
Furthermore, the group presented a poster concerning "Prospective Validation of Serum Protein Biomarkers for Detection of Acute Liver Rejection – Initial Results with CXCL9 and CD44"
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TTS Postgraduate Weekend
The postgraduate program offers an up-to-date overview on pressing clinical and basic science topics with relevance for all participants of the Berlin 2012 meeting. The program is designed to provide clinicians with an overview of the most recent advances in basic research in a bench-to-bedside approach. Updates on immunosuppression, organ-specific processes, organ supply, immune monitoring and the relevance of animal models in transplantation will help both clinicians and researchers with basic information aligning their efforts and providing the best care of transplant patients in the years ahead.
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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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TTS 2012 Abstract submission now open!
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Please join the mailing list and follow us via Twitter @TTS2012 for latest information concerning the 24th International Congress of The Transplantation Society to be held in Berlin, Germany from July 15th - 19th 2012 !
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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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TTS 2012: Follow us via Twitter!
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The 24th International Congress of The Transplantation Society to be held in Berlin, Germany from July 15th - 19th 2012 is designed for physicians, surgeons, scientists and organ procurement personnel, who are interested in clinical and research aspects of solid organ, cell and tissue transplantation. The program is developed to encourage the exchange of new scientific and clinical information, and support an interchange of opinions regarding care and management issues, as well as socioeconomic, ethical and regulatory issues relevant to transplantation.
In addition to the classical types of scientific sessions including plenary sessions, symposia, workshops and poster presentations, we will also offer new types of scientific sessions within the Forum Futurum.
The Forum Futurum is a forum integrated in the congress that will take place on three days. Each day is assigned to a topic and the forum is dedicated to cutting-edge science in our field. The topics are Regenerative Medicine, Imaging and Tailored Pharmacotherapy.
The Forum Futurum is designed to be a highly interactive communication space where companies can introduce their products and conversations about the latest research are stirred. In a futuristic environment the Forum Futurum contributes to an extraordinary TTS 2012 Exhibition experience and will provide exhibitors the opportunity to highlight new product information to physicians and health care professionals. Enhance the educational element of your company's noteworthy products and services with a presentation in the Forum Futurum. The Forum Futurum provides exhibitors with a unique and effective marketing opportunity to hold live promotional presentations or activities designed to raise awareness of featured services and products.
The Forum Futurum will make its debut in the TTS 2012 Exhibit Hall, featuring experts from companies and scientific groups providing state-of-the-art content-led information about new technologies, products and ideas. The Forum Futurum will be open July 16th – July 18th. Every day is dedicated to one emerging field in transplantation:
Monday, July 16th, 2012: One Day on Regenerative Medicine
Tuesday, July 17th, 2012: One Day on Imaging
Wednesday, July 18th, 2012: One Day on Tailored Pharmacotherapy
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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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Profiles of microRNA after rat partial hepatectomy
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The website of the 24th International Congress of The Transplantation Society is online! Please go to www.transplantation2012.org for more information.
Following the exceptionally successful meetings in Boston, Sydney and Vancouver, we would like to welcome you to a city which twenty years after reunification has evolved into one of the most important capitals of Europe. Once the capital of Prussia and leading cultural centre of the 1920s, today the new capital of Germany is characterized by its dazzling modernity and breathtaking architecture. Berlin is young, dynamic and bursting with joie de vivre. Few cities has been shaped to such an extent by history and undergone as much major transformation as Berlin. “Berlin is always in the process of becoming”, remarked historian Karl Scheffler. Even in the 21st century transplantation still is in a process of becoming, too. Therefore, the 24th International Congress of The Transplantation Society will promote the dialogue of experts from around the world. An attractive scientific program will be developed together with the Deutsche Transplantationsgesellschaft (DTG).
The 24th Congress is designed for physicians, surgeons, scientists and organ procurement personnel, who are interested in clinical and research aspects of solid organ, cell and tissue transplantation. The program is developed to encourage the exchange of new scientific and clinical information, and and support an interchange of opinions regarding care and management issues, as well as socioeconomic, ethical and regulatory issues relevant to transplantation.
In addition to the classical types of scientific sessions including plenary sessions, symposia, workshops and poster presentations, we will also offer new types of scientific sessions within the Forum Futurum focusing on Tailored Pharmacotherapy, Imaging and Regenerative Medicine. All of this is designed to develop a highly interactive forum to discuss cutting-edge science in our field.
We therefore cordially invite you and your colleagues together with your friends and family to come to Berlin. Your active participation in the scientific program will be the fundament for a successful event in 2012.
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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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Labelling of hepatocytes in suspension culture
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Our latest paper on "Monitoring of liver cell transplantation in a preclinical swine model using magnetic resonance imaging" has been accepted for publication in CELL Medicine (Part B of CELL TRANSPLANTATION). Authors are Nathanael Raschzok, Ulf Teichgräber, Nils Billecke, Anja Zielinski, Kirsten Steinz, Nora N. Kammer, Mehmet H. Morgul, Sarah Schmeisser, Michaela K. Adonopoulou, Lars Morawietz, Bernhard Hiebl, Ruth Schwartlander, Wolfgang Rüdinger, Bernd Hamm, Peter Neuhaus and Igor M. Sauer. The study was based on the excellent colaboration with the department of Radiology and the Institute of Pathology, both Charité - Campus Mitte, Universitätsmedizin Berlin, Berlin, Germany, the Centre for Biomaterial Development and Berlin-Brandenburg Centre for Regenerative Therapies (BCRT), Institute for Polymer Research, GKSS Research Centre Geesthacht GmbH, Teltow, Germany, the Department of Materials, ETH Zurich, Zurich, C Switzerland, and Cytonet GmbH, Weinheim, Germany.
Liver cell transplantation (LCT) is a promising treatment approach for certain liver diseases, but clinical implementation requires methods for non-invasive follow-up. Labeling with superparamagnetic iron oxide particles can enable the detection of cells with magnetic resonance imaging (MRI). We investigated the feasibility of monitoring transplanted liver cells by MRI in a preclinical swine model and used this approach to evaluate different routes for cell application. Liver cells were isolated from landrace piglets and labeled with micron-sized iron oxide particles (MPIO) in adhesion. Labeled cells (n = 10), native cells (n = 3) or pure particles (n = 4) were transplanted to minipigs via intraportal infusion into the liver, direct injection into the splenic parenchyma, or intra-arterial infusion to the spleen. Recipients were investigated by repeated 3.0 Tesla MRI and computed tomography angiography up to 8 weeks after transplantation. Labeling with MPIO, which are known to have a strong effect on the magnetic field, enabled non-invasive detection of cell aggregates by MRI. Following intraportal application, which is commonly applied for clinical LCT, MRI was able to visualize the microembolization of transplanted cells in the liver that were not detected by conventional imaging modalities. Cells directly injected into the spleen were retained, whereas cell infusions intraarterially into the spleen led to translocation and engraftment of transplanted cells in the liver, with significantly fewer microembolisms compared to intraportal application. These findings demonstrate that MRI can be a valuable tool for non-invasive elucidation of cellular processes of LCT and - if clinically applicable MPIO are available - for monitoring of LCT under clinical conditions. Moreover, the results clarify mechanisms relevant for clinical practice of LCT, suggesting that the intra-arterial route to the spleen deserves further evaluation.
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SPAD in children with acute liver failure
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Hannelore Ringe published the investigations concerning the applicability, efficacy, and safety of single-pass albumin dialysis in children ("Continuous veno-venous single-pass albumin hemodiafiltration in children with acute liver failure." Pediatr Crit Care Med. 2010 Oct 1. [Epub ahead of print]). Co-authors are Varnholt V, Zimmering M, Luck W, Gratopp A, König K, Reich S, Sauer IM, Gaedicke G, and Querfeld U.
The paper reports on a retrospective data review of uncontrolled clinical data of an university-based pediatric intensive care unit collaborating with a local center for liver transplantation. Nine children, aged 2 to 15 yrs, who were treated with single-pass albumin dialysis for acute liver failure of various origins under a compassionate-use protocol between 2000 and 2006. All patients met high-urgency liver transplantation criteria. Single-pass albumin dialysis was performed as rescue therapy for children with acute liver failure. The decrease in hepatic encephalopathy (grades 1-4) and the serum levels of bilirubin, bile acids, and ammonium were measured to assess the efficacy of detoxification. As a measure of liver synthesis function, thromboplastin time and fibrinogen were analyzed. The safety of the procedure was assessed by documenting adverse effects on mean arterial blood pressure, platelet count, and clinical course. Seven out of nine patients were bridged successfully to either native organ recovery (n = 1) or liver transplantation (n = 7), one of them twice. Six out of nine patients undergoing single-pass albumin dialysis (ten treatments) survived. In six patients, hepatic encephalopathy could be reduced at least by one degree. Ammonium, bilirubin, and bile acid levels decreased in all patients. One patient had an allergic reaction to albumin. In childhood acute liver failure, treatment with single-pass albumin dialysis was generally well tolerated and seems to be effective in detoxification and in improving blood pressure, thus stabilizing the critical condition of children before liver transplantation and facilitating bridging to liver transplantation. It may be beneficial in avoiding severe neurologic sequelae after acute liver failure and thereby improve survival. Single-pass albumin dialysis is an inexpensive albumin-based detoxification system that is easy to set up and requires little training. Whether and to what extent single-pass albumin dialysis can support children with acute liver failure until native liver recovery remain unclear.
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Presentations at this year´s XXXVII ESAO Congress
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At this year's XXXVII ESAO Congress, in Skopje. R. Macedonia, Wiebke Werner and Nathanael Raschzok gave oral presentations.
Nathanael Raschzok presented data on "In vitro evaluation of magnetic resonance imaging contrast agents for labeling of human liver cells" (N. Raschzok, D. A. Muecke, M. Adonopoulou, N. Billecke, A. Zielinski, W. Werner, U. Teichgraeber, I. M. Sauer). Wiebke Werner reported on "Temporal microRNA gene expression profiles of the regenerating rat liver after partial hepatectomy" (W. Werner, N. Raschzok, H. Sallmon, N. Billecke, C. Dame, P. Neuhaus, I. M. Sauer), a joint project of the Department of Neonatology, Charité, and our group.
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XXIII International Congress of TTS
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Nathanael Raschzok presented our latest results with labeled hepatocytes in the pig model at the XXIII International Congress of The Transplantation Society in Vancouver, Canada. The oral presentation was entitled "MRI enables monitoring of transplanted hepatocytes in a preclinical large animal model" (N. Raschzok, N. Billecke, A. Zielinski, K. Steinz, N.N. Kammer, S. Schmeisser, M.H. Morgul, M.K. Adonopoulou, J. Pinkernelle, L. Morawietz, B. Hiebl, W. Rüdinger, U. Teichgräber, P. Neuhaus, I.M. Sauer).
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The 60th Lindau Nobel Laureate Meeting
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The 2010 Lindau Meeting took place from June 27 till July 2. The 3rd interdisciplinary meeting brought together more than 650 young researchers from around the globe with 59 Nobel Laureates from the fields of physiology or medicine, physics and chemistry.
The Lindau Nobel Laureate Meetings provide a globally recognised forum for the transfer of knowledge between generations of scientists. They inspire and motivate Nobel Laureates and international Best Talents. Lectures of Nobel Laureates reflect current scientific topics and present relevant fields of research of the future. In panel discussions, seminars and during the various events of the social program young researchers nominated by a worldwide network of Academic Partners interact with Nobel Laureates.
Taking into account the national selection procedures, in excess of 20,000 young researchers apply to attend each Meeting. After Ruth Schwartländer attended in 2008 this year Nathanael Raschzok was chosen and received an invitation to Lindau.

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Hypothermia-induced cell protection & microglial cells
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The European Journal of Neuroscience published the paper "Mechanisms of hypothermia-induced cell protection mediated by microglial cells in vitro" First author is Antje Diestel from Katharina Schmitt's group - co-authors are Silke Troeller, Nils Billecke, Igor M. Sauer, Felix Berger and Katharina R. L. Schmitt.
Despite the widespread interest in the clinical applications of hypothermia, the cellular mechanisms of hypothermia-induced neuroprotection have not yet been clearly understood. Therefore, the aim of this study was to elucidate the cellular effects of clinically relevant hypothermia and rewarming on the morphological and functional characteristics of microglia. Microglial cells were exposed to a dynamic cooling and rewarming protocol. For stimulation, microglial cells were treated with 1 μg/mL lipopolysaccharide (LPS). We found that hypothermia led to morphological changes from ramified to ameboid cell shapes. At 2 h after hypothermia and rewarming, microglial cells were again ramified with extended branches. Moreover, we found enhanced cell activation after rewarming, accompanied by increased phagocytosis and adenosine triphosphate consumption. Interestingly, hypothermia and rewarming led to a time-dependent significant up-regulation of the anti-inflammatory cytokines interleukin-10 and interleukin-1 receptor antagonist in stimulated microglial cells. This is in line with the reduced proliferation and time-dependent down-regulation of the pro-inflammatory cytokines tumor necrosis factor-alpha and monocyte chemotactic protein-1 in comparison to normothermic control cells after LPS stimulation. Furthermore, degradation of the inhibitor of the nuclear transcription factor-kappaB (IkappaB-alpha) was diminished and delayed under conditions of cooling and rewarming in LPS-stimulated microglial cells. Thus, our results show that hypothermia and rewarming activate microglial cells, increase phagocytosis and shift the balance of cytokine release in stimulated microglial cells towards the anti-inflammatory cytokines. This could be a new cellular mechanism of hypothermia-induced neuroprotection mediated by activated microglial cells.
European Journal of Neuroscience, 2010; 31: 779-787
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Charité's 300-year anniversary in 2010
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At the Charité, our scientists and physicians engage in state-of-the-art research, patient care and education. More than half of the German Nobel Prize winners in medicine and physiology come from the Charité, among them Emil von Behring, Robert Koch and Paul Ehrlich. The Charité also has an international reputation for excellence in training. It extends over four campuses with more than 100 clinics and institutes bundled under 17 CharitéCenters. The Charité has a turnover of nearly 1 billion euros per year, and it is one of the largest employers in Berlin with 14,500 employees.
In 2010, the Charité will celebrate its 300-year anniversary and will do everything to make this historical event a memorable one.
Short film covering the Charité - Universitätsmedizin celebrating its 300-year anniversary (47.91 MB)

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Modified nanoparticles & multimodal imaging
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Lars Stelter's studies on In vitro and in vivo detectability of modified superparamagnetic nanoparticles for multimodal imaging using fluorescence microscopy, 3T MRI and animal PET are published in the latest issue of Molecular Imaging & Biology (Mol Imaging Biol. 2010 Jan-Feb;12(1):25-34). Co-authors are Jens Pinkernelle, Roger Michel, Ruth Schwartländer, Nathanael Raschzok, Mehmet H. Morgul, Martin Koch, Timm Denecke, Holger Amthauer, Juri Ruf, Andreas Jordan, Bernd Hamm, Igor M. Sauer, Ulf Teichgräber.
Cell transplantation is a major field in regenerative medicine and a promising alternative to whole organ transplantation. However, the process of cell engraftment is not yet fully understood and the hitherto achieved clinical outcome is limited. The aim of our study was to modify an aminosilan-coated nanoparticle for cell labeling and make it applicable for multimodal imaging using MRI, PET and fluorescent imaging. HIV-1 tat, linked FITC, and Gallium-68 were covalently bound to the particle and injected into Wistar rats. Animal-PET imaging was performed followed by MRI at 3.0T. Hepatic accumulation of the particles was proven by radionuclide distribution after 10 minutes in PET as well as in MRI over a 24 hour-period. Histological workup of the liver also revealed content of iron oxide particles in the reticuloendothelial system. Adjacent in vitro studies incubating hepatogenic HuH7 cells with the particles showed a rapid intracellular accumulation, clearly detectable by fluorescence microscopy and MRI. In conclusion our modified nanoparticle is stable under in vitro and in vivo conditions and is applicable for multimodal molecular imaging. Cellular labeling with this particle is possible and might help to get new insights into understanding the process of cell transplantation.
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XXIII International Congress of TTS
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The XXIII International Congress of The Transplantation Society, the leading international congress on transplantation biology and medicine, will be held in Vancouver, Canada from 15 - 19 August 2010. The translational program will draw together experts from around the world, and will encompass innovations in genomics and proteomics, molecular analyses of human diseases, innovations in biological and pharmacological immunosuppression, novel approaches to tolerance induction, technical advances in robotic surgery and imaging, advances in clinical practice and many other topics at the cutting edge of stem-cell, cellular and solid organ transplantation.
The XXIII Congress will be one of the largest and most exciting international gatherings of clinicians and scientists in the field of transplantation, drawing more than 4,000 delegates from all parts of the world. The international delegation will enjoy a stellar Scientific Program, commencing with a comprehensive and cutting-edge Postgraduate Education Program on Saturday 14th August and Sunday 15th August, and continuing with a panoply of outstanding plenary symposia, state of the art lectures, individual scientific presentations, and thematic symposia from Monday 16th August to Thursday 19th August inclusive.
The 2010 Congress will provide an outstanding opportunity for networking with colleagues and leading experts, and for sharing and discussing clinical advances, late-breaking discoveries and therapeutic advances in this field.
More information is available via www.transplantation2010.org. Furthermore, you may download the 2nd announcement here.
Important dates:
Abstract Submission Opens: October 2009
Online Registration Opens: November 2009
Abstract Submission Deadline: 5 March 2010
Author Notification of Acceptance: 7 May 2010
Early Registration Deadline: 4 June 2010
Late Breaking Abstract Deadline: 11 June 2010
Hotel Reservation Deadline: 25 June 2010
Regular Registration Deadline: 16 July 2010

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Haluk Morgül defended thesis "magna cum laude"
Haluk Morgül successfully defended his medical doctoral thesis "magna cum laude".
After years of extremely fruitful research in the field of liver support, hepatocyte isolation and cell imaging via MRI he is (co-)author of 5 papers in peer reviewed journals (with more to come)!
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cBAL111
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Tanja Deurholt's paper on "Novel immortalized human fetal liver cell line, cBAL111, has the potential to differentiate into functional hepatocytes" is published in BMC Biotechnology. Co-authors are Niek P. van Til, Aniska A. Chhatta, Lysbeth ten Bloemendaal, Ruth Schwartlander, Catherine Payne, John N. Plevris, Igor M. Sauer, Robert A.F.M. Chamuleau, Ronald P.J. Oude Elferink, Jurgen Seppen, and Ruurdtje Hoekstra.
A clonal cell line that combines both stable hepatic function and proliferation capacity is desirable for in vitro applications that depend on hepatic function, such as pharmacological or toxicological assays and bioartificial liver systems. The article describes the generation and characterization of a clonal human cell line for in vitro hepatocyte applications.Cell clones derived from human fetal liver cells were immortalized by over-expression of telomerase reverse transcriptase. The resulting cell line, cBAL111, displayed hepatic functionality similar to the parental cells prior to immortalization, and did not grow in soft agar. Cell line cBAL111 expressed markers of immature hepatocytes, like glutathione S transferase and cytokeratin 19, as well as progenitor cell marker CD146 and was negative for lidocaine elimination. On the other hand, the cBAL111 cells produced urea, albumin and cytokeratin 18 and eliminated galactose. In contrast to hepatic cell lines NKNT-3 and HepG2, all hepatic functions were expressed in cBAL111, although there was considerable variation in their levels compared with primary mature hepatocytes. When transplanted in the spleen of immunodeficient mice, cBAL111 engrafted into the liver and partly differentiated into hepatocytes showing expression of human albumin and carbamoylphosphate synthetase without signs of cell fusion. This novel liver cell line has the potential to differentiate into mature hepatocytes to be used for in vitro hepatocyte applications.
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