Rebeka Major: BIH-Promotionsstipendium

Rebeka Major successfully applied for the BIH-Promotionsstipendium grant. Her work will focus in the role of the INDY („I’m Not Dead Yet“) gene in liver regeneration – a project in cooperation with Prof. A. Birkenfeld, Universitätsklinikum Carl Gustav Carus in Dresden.
In the Berlin Institute of Health (BIH), the Max Delbrück Center for Molecular Medicine (MDC) and the Charité - Universitätsmedizin Berlin have joined forces. The core idea is to combine translational research with an overarching systems medicine approach to bridge the gap between basic research and clinical application.

ESAO 2015 in Leuven, Belgium

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Presentations at DTG 2014

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Nathanael Raschzok presented his poster „Protein biomarkers for diagnosis and prediction of acute cellular rejection after liver transplantation“, Benjamin Strücker his work entitled „Oszillierende Druckschwankung verbessern signifikant die Ratten- und Schweineleber Dezellularisierung“ and Rosa Schmuck her posters „Risk of postoperative infections after LTX rises with MELD score“ and „Protein biomarkers in bile as a diagnostic tool after liver transplantation“.

Ben Strücker: Charité Clinical Scientist

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Dr. med Benjamin Strücker successfully applied for the Charité Clinical Scientist 2015 program.

His project is entitled „Humanized Porcine Liver““. Clinical mentor is Prof. Dr. Johann Pratschke, scientific mentors is Priv.-Doz. Dr. med Igor M. Sauer.

The program is supported by Stiftung Charité which was endowed by the entrepreneur Johanna Quandt in order to promote biomedical "knowledge entrepreneurs" that is, change makers in biomedicine at the Charité. The goal of this program is to develop new career paths in clinical specialist medical training. The focus of the training program "Clinical Scientist" is translational research ("bench-to-bedside") which will be realized by a reduction in clinical routine and an improved curriculum with defined goals.

Sham Laparotomy and microRNA Expression in Rats

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BMC Research Notes accepted our latest paper on „Independent Effects of Sham Laparotomy and Anesthesia on Hepatic microRNA Expression in Rats“ for publication.

Studies on liver regeneration following partial hepatectomy (PH) have identified several microRNAs (miRNAs) that show a regulated expression pattern. These studies involve major surgery to access the liver, which is known to have intrinsic effects on hepatic gene expression and may also affect miRNA screening results. We performed two-third PH or sham laparotomy (SL) in Wistar rats to investigate the effect of both procedures on miRNA expression in liver tissue and corresponding plasma samples by microarray and qRT-PCR analyses. As control groups, non-treated rats and rats undergoing anesthesia only were used. We found that 49 out of 323 miRNAs (15%) were significantly deregulated after PH in liver tissue 12 to 48 hours postoperatively (>20% change), while 45 miRNAs (14%) were deregulated following SL. Out of these miRNAs, 10 miRNAs were similarly deregulated after PH and SL, while one miRNA showed opposite regulation. In plasma, miRNA upregulation was observed for miR-133a and miR-133b following PH and SL, whereas miR-100 and miR-466c were similarly down-regulated following anesthesia and surgery. We show that miRNAs are indeed regulated by sham laparotomy and anesthesia in rats. These findings illustrate the critical need for finding appropriate control groups in experimental surgery.

Authors are W. Werner, H. Sallmon, A. Leder, S. Lippert, A. Reutzel-Selke, M.H. Morgül, S. Jonas, S. Dame, P. Neuhaus, J. Iacomini, S.G. Tullius, I.M. Sauer and N. Raschzok.

Textbook of Organ Transplantation Set

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Brought to you by the world’s leading transplant clinicians, Textbook of Organ Transplantation provides a complete and comprehensive overview of modern transplantation in all its complexity, from basic science to gold-standard surgical techniques to post-operative care, and from likely outcomes to considerations for transplant program administration, bioethics and health policy.
Beautifully produced in full color throughout, and with over 600 high-quality illustrations, it successfully
- Provides a solid overview of what transplant clinicians/surgeons do, and with topics presented in an order that a clinician will encounter them.
- Presents a holistic look at transplantation, foregrounding the interrelationships between transplant team members and non-surgical clinicians in the subspecialties relevant to pre- and post-operative patient care, such as gastroenterology, nephrology, and cardiology.
- Offers a focused look at pediatric transplantation, and identifies the ways in which it significantly differs from transplantation in adults.
- Includes coverage of essential non-clinical topics such as transplant program management and administration; research design and data collection; transplant policy and bioethical issues.

Editors are Allan D. Kirk, Stuart J. Knechtle, Christian P. Larsen, Joren C. Madsen, Thomas C. Pearson, and Steven A. Webber.
I.M. Sauer, N. Raschzok und P. Neuhaus contributed chapter 47: „Artificial Liver, In Vivo Tissue Engineering, and Organ Printing – Solutions for Organ Scarcity“

The Wiley-Blackwell book (ISBN: 978-1-118-87014-3, 1880 pages) is available here.

Decellularization of porcine livers

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Ben Strücker’s paper entitled „Porcine liver decellularization under oscillating pressure conditions – A technical refinement to improve the homogeneity of the decellularization process“ has been accepted for publication in Tissue Engineering, Part C: Methods.
Co-authors are K. Hillebrandt, R. Voitl, A. Butter, R.B. Schmuck, A. Reutzel-Selke, D. Geisel, K. Joehrens, P.A. Pickerodt, N. Raschzok, G. Puhl, P. Neuhaus, J. Pratschke, and I.M. Sauer.

Decellularization and recellularization of parenchymal organs may facilitate the generation of autologous functional liver organoids by repopulation of decellularized porcine liver matrices with induced liver cells. We present an accelerated (7 h overall perfusion time) and effective protocol for human scale liver decellularization by pressure-controlled perfusion with 1% Triton X-100 and 1% SDS via the hepatic artery (120 mmHg) and portal vein (60 mmHg). In addition, we analyzed the effect of oscillating pressure conditions on pig liver decellularization (n=12). The proprietary perfusion device used to generate these pressure conditions mimics intra-abdominal conditions during respiration to optimize microperfusion within livers and thus optimize the homogeneity of the decellularization process. The efficiency of perfusion decellularization was analyzed by macroscopic observation, histological staining (H&E, Sirius red, Alcian blue), immunohistochemical staining (collagen IV, laminin, fibronectin) and biochemical assessment (DNA, collagen, glycosaminoglycans) of decellularized liver matrices. The integrity of the extracellular matrix post-decellularization was visualized by corrosion casting and three-dimensional CT scanning. We found that livers perfused under oscillating pressure conditions (P+) showed a more homogenous course of decellularization and contained less DNA compared to livers perfused without oscillating pressure conditions (P-). Microscopically, livers from the (P-) group showed remnant cell clusters, while no cells were found in livers from the (P+) group. The grade of disruption of the ECM was higher in livers from the (P-) group, although the perfusion rates and pressure did not significantly differ. Immunohistochemical staining revealed that important matrix components were still present after decellularization. Corrosion casting showed an intact vascular (portal vein and hepatic artery) and biliary framework. In summary, the presented protocol for pig liver decellularization is quick (7 h) and effective. The application of oscillating pressure conditions improves the homogeneity of perfusion and thus the outcome of the decellularization process.

5th EPITA Winter Symposium

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25th European Students‘ Conference

esc The ESC is one of the largest student-run biomedical conferences worldwide. It was established in 1989 as one of the first student conferences facilitating exchange between Western and Eastern Europe. Until today, it aims to foster international understanding within the young scientific community, and to promote high-quality science among young researchers in the biomedical field.

This year’s lecture series “Rethinking Medical Research – how do we achieve innovation?” will explore the dichotomy of medical advances by looking at both the opportunities and challenges that are presented to researchers and physicians. With topics ranging from open access policies, pharmaceutical innovations, and revolutionary health policies to advances in global health – we hope that this year’s topic will both challenge and inspire our participants!
The conference will take place from September 17th – 20th at the Virchow Klinikum Campus of the Charité Universitätsmedizin in Berlin, Germany.

More information here!

N. Raschzok Guest Editor – Call for Papers

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Pluripotent stem cells have been an important tool for researches in hepatology, starting with mouse embryonic stem cells and transgenesis. Together, with other animal models, they largely contributed to our current knowledge in hepatic cells development and disease modeling. Therefore, with the possibility to manipulate human embryonic stem cells and more recently human induced pluripotent stem cells, there was an existing substratum to study these processes in a human environment, which contributed to the tremendous explosion of the emerging Liver Regenerative Medicine field. The use of such cells in the last few years has been already at the origin of numerous breakthroughs in disease modeling, host-pathogen interactions studies, or liver bioengineering and many are to come.

Investigators are invited to participate in a special issue on „Human Pluripotent Stem Cells in Hepatic Development, Liver Reconstruction and Disease Modeling“ through original research articles at the forefront of this fast pace moving field as well as reviews describing current and forthcoming challenges.

Lead Guest Editor is Karim Si-Tayeb (Institute of the Thorax, Nantes). Guest Editors are Gareth Sullivan (Institute of Basic Medical Sciences, University of Oslo), Robert Schwartz (Weill Cornell Medical College, Cornell University, New York), Nathanael Raschzok (Charité – Universitaetsmedizin Berlin), and Tamir Rashid (King's College London).

Manuscript Due: Friday, 23 January 2015
First Round of Reviews: Friday, 17 April 2015
Publication Date: Friday, 12 June 2015


More information ...

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.

Congratulations !

WTC 2014 in San Francisco

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Ben Strücker presented the latest results on „Perfusion Decellularization of Pig and Rat Livers Applying Undulating Surrounding Pressure Conditions“. Co-authors were A. Butter, K. Hillebrandt, R. Voitl, D. Polenz, A. Reutzel-Selke, K. Joehrens, D. Geisel, N. Raschzok, P. Neuhaus, J. Pratschke and I.M. Sauer.

Nathanael Raschzok presentation was entitled: „Perioperative Serum Levels of CXCL9 and CD44 Predict the Risk of Acute Cellular Rejection in Liver Graft Recipients“. Co-authors were N. Raschzok, A. Reutzel-Selke, R. Schmuck, M. Morgul, M. Bartels, G. Puhl, D. Seehofer, M. Bahra, A. Pascher, P. Neuhaus, J. Pratschke and I.M. Sauer.

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 !

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. 

Charité Clinical Scientist Summer Symposium

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Please check the program here...

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 here.

yESAO 2014

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Decellularization of rat liver – New time lapse video

„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
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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.

Neujahrsessen 2014

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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.
Please, check the ESAO website (www.esao.org) for the actual availability of the Congress website (www.esao2014.org).