News

DFG | Grant for Machine Perfusion RCT
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The German Research Foundation (Deutsche Forschungsgemeinschaft – DFG) s sponsoring a multicenter randomized controlled clinical trial by Prof. Dr. Georg Lurje entitled "End-ischemic hypothermic oxygenated (HOPE) or normothermic machine perfusion (NMP) compared to conventional cold storage (CCS) in donation after brain death (DBD) liver transplantation; a prospective multicenter randomized controlled trial (HOPE-NMP)".

The purpose of this study is to test the effects of end-ischemic NMP versus end-ischemic HOPE technique in a multicentre prospective randomized controlled clinical trial (RCT) on ECD liver grafts in DBD liver-transplantation (HOPE-NMP). Two-hundred-thirteen (n = 213) human whole organ liver grafts will be submitted to either NMP (n = 85) or HOPE (n = 85) directly before implantation and going to be compared to a control-group of patients (n = 43) transplanted with static cold storage preserved ECD-allografts. Primary (surgical complications as assessed by the comprehensive complication index [CCI]) and secondary (graft- and patient survival, hospital costs, hospital stay) endpoints are going to be analysed.


Congratulations !
DFG Walter-Benjamin grant for the investigation of sex as a biological variable in alloimmunity
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With a DFG Walter-Benjamin grant Dr. med. Friederike Martin will join the laboratory of Transplant Surgery Research at Harvard under the direction of Professor Stefan G. Tullius in Boston to investigate the role of biological sex for transplantation outcome.

Influences of donor and recipient sex on transplantation outcome have been described manifold, as well as an influence of sex hormones on the innate and adaptive immune response. So far, research, investigating the impact of sex hormones and different sex- and age-dependent sex-hormone levels on alloimmune response after solid organ transplantation is lacking. The aim of the project “Sex as a biological Variable in Alloimmunity” is, to delineate the impact of sex hormones and especially estrogens and age-dependent changes in estrogen-levels on alloimmune response after allogenic transplantation.  The project is based on the publication “Recipient sex and estradiol levels affect transplant outcomes in an age-specific fashion” published in the AJT in 2021 by the workgroup of Prof. Tullius.

Friederike, who already received the Sanofi Women in Transplantation fellowship grant for research in gender and sex in transplantation in 2021, will work as a Postdoc on this project in the Tullius Lab for an expected 2 years period, starting in January 2023.


Congratulations!
2022 TTS Mentee-Mentor-Award
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Dr. Barbara Kern und Prof. Dr. Stefan G. Tullius received the 2022 Mentee-Mentor-Award of The Transplant Society during the 29th Conference in Buenos Aires.

In collaboration with National and International Societies, TTS acknowledges and recognizes the efforts of scientists who have advanced our understanding of transplantation science and fostered the development of young investigators.
The Mentee-Mentor Awards are designed to encourage dialogue and interactions between trainees and established investigators, and provide financial support for their joint participation in the Congress.

Congratulations!
Inaugural Lectures
We are pleased to announce that four members of staff have successfully completed their habilitation work in the last few months!

On
Friday, 08.07.2022 at 15:00 in lecture hall 3 of the teaching building (Forum 3, CVK), Dr. med. habil. Linda Feldbrügge and Dr. med. habil. Paul Ritschl will give their inaugural lectures entitled "New role of surgery in modern tumour and transplant medicine".

On
Friday, 15.07.2022 at 16:30 in the Friedrich Kopsch lecture theatre of the Anatomy Department at Campus Mitte Dr. med. habil. Eva Dobrindt and Dr. med. habil. Rosa Schmuck will present their inaugural lectures with the topic "An Operating Room of One's Own - The Surgeon in Ancient Tradition and Modernity".
This will be followed by a small reception in the park in front of the venue.
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Robert-Koch-Prize awarded to Simon Moosburner
Today, Dr. med. Simon Moosburner received the Robert-Koch-Prize for one of the three best dissertations of the Charité - Universitätsmedizin Berlin in 2020 for his thesis titled  "Erweiterung der Spenderpopulation bei Lebertransplantation: Klinischer Bedarf und Entwicklung eines Kleintier-Lebermaschinenperfusionssystems (Expanding the donor pool for liver transplantation: clinical need and development of small animal liver perfusion system)".


Congratulations!
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BIH Charité Clinician Scientist Symposium in Honor and Memory of Duška Dragun
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28 May 2021 - 29 May 2021
BIH Charité Clinician Scientist Symposium in Honor and Memory of Duška Dragun

The symposium is composed of several components: First and foremost, it will commemorate Prof. Duška Dragun, the former Director of the BIH Biomedical Innovation Academy (BIA) and Director of the BIH Charité Clinician Scientist Program, who passed away in December 2020, and will be joined by stakeholders from academia and science policy. In addition, there will be scientific sessions, which will form tandems of program fellows and invited speaker. During a digital certificate ceremony on the evening of 28 May 2021, some 50 alumni will be bid farewell. The event language is English.

When
28 and 29 May 2021
10:00 - 6:30 pm

How
Online Event (semi-digital)

Registration
To receive the login link please register here.
Advanced Clinician Scientists
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Priv.-Doz. Dr. Nathanael Raschzok and Priv.-Doz. Dr. Felix Krenzien successfully applied for the BIH Charité Advanced Clinician Scientist Pilot Programme (AdCSP) in a highly competitive process.

The BIH Charité AdCSP is designed as a career-phase-specific, sustainable funding programme that aims to closely interlink individual and institutional funding. The primary goal of the programme is to simultaneously incentivise the fellows and recognise the permissive academic culture of the respective clinics or institutes. Like the BIH Charité Clinician Scientist Programme (CSP) and the "Digital Clinician Scientist Programme" (DCSP), which has been additionally funded by the DFG since 2019, it is intended to be open to all clinical disciplines and to offer multiple networking opportunities for the funded fellows and participating clinics and institutes.

Congratulations!
Recellularization of decellularized bovine carotid arteries
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"In vitro recellularization of decellularized bovine carotid arteries using human endothelial colony forming cells" was published in the latest issue of Journal of Biological Engineering.
Many patients suffering from peripheral arterial disease (PAD) are dependent on bypass surgery. However, in some patients no suitable replacements (i.e. autologous or prosthetic bypass grafts) are available. Advances have been made to develop autologous tissue engineered vascular grafts (TEVG) using endothelial colony forming cells (ECFC) obtained by peripheral blood draw in large animal trials. Clinical translation of this technique, however, still requires additional data for usability of isolated ECFC from high cardiovascular risk patients.
Bovine carotid arteries (BCA) were decellularized using a combined SDS (sodium dodecyl sulfate) -free mechanical-osmotic-enzymatic-detergent approach to show the feasibility of xenogenous vessel decellularization. Decellularized BCA chips were seeded with human ECFC, isolated from a high cardiovascular risk patient group, suffering from diabetes, hypertension and/or chronic renal failure. ECFC were cultured alone or in coculture with rat or human mesenchymal stromal cells (rMSC/hMSC). Decellularized BCA chips were evaluated for biochemical, histological and mechanical properties. Successful isolation of ECFC and recellularization capabilities were analyzed by histology.

Decellularized BCA showed retained extracellular matrix (ECM) composition and mechanical properties upon cell removal. Isolation of ECFC from the intended target group was successfully performed (80% isolation efficiency). Isolated cells showed a typical ECFC-phenotype. Upon recellularization, co-seeding of patient-isolated ECFC with rMSC/hMSC and further incubation was successful for 14 (n = 9) and 23 (n = 5) days. Reendothelialization (rMSC) and partial reendothelialization (hMSC) was achieved. Seeded cells were CD31 and vWF positive, however, human cells were detectable for up to 14 days in xenogenic cell-culture only. Seeding of ECFC without rMSC was not successful.

Using our refined decellularization process we generated easily obtainable TEVG with retained ECM- and mechanical quality, serving as a platform to develop small-diameter (< 6 mm) TEVG. ECFC isolation from the cardiovascular risk target group is possible and sufficient. Survival of diabetic ECFC appears to be highly dependent on perivascular support by rMSC/hMSC under static conditions. ECFC survival was limited to 14 days post seeding.
Authors are N. Seiffert, P. Tang, E. Keshi, A. Reutzel-Selke, S. Moosburner, H. Everwien, D. Wulsten, H. Napierala, J. Pratschke, I.M. Sauer, K. Hillebrandt, and B. Struecker.
J Biol Eng 15, 15 (2021). https://doi.org/10.1186/s13036-021-00266-5
Position for Research Associate / Research Fellow
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Priv.-Doz. Dr. Nathanael Raschzok and his team are working on strategies for (re-) conditioning of marginal liver grafts by ex vivo liver machine perfusion. The aim for the proposed job offer, which is funded by grants of the Else Kröner-Fresenius-Stiftung, is to make steatotic liver grafts, which are usually discarded from transplantation due to the high risk for the recipient, acceptable for transplantation. We have already established a small animal model of ex vivo liver machine perfusion as well as transplantation. Aim of this project is to test a clinically approved drug in dose-response studies (based on preliminary data), followed by in vivo studies in the rat liver transplantation model.

Your responsibility will be:
  • Organ perfusion of murine livers in our established small animal modell for ex vivo liver machine perfusion
  • Support of in rat liver transplantation experiments
  • Organ recovery and transplantation (not mandatory)
  • Biochemical analysis of the perfusat and the lipid metabolism (ELISA), tissue analysis (qRT-PCR, Wester Blot, immunochemistry, immunofluorescence)
  • We fully support the application and submission of a doctoral thesis (e.g. Dr. rer.medic or MD/PhD)
Require­ments
  • Degree in biology, biochemistry, biotechnology or medicine
  • Pevious experience in molecular cell biology and/or proteinbiochemistry, or surgical research
  • Proficiency in standard methods, especially histology, immunhistochemistry, qPCR, FACS, microscopy, cell culture/cell isolation
  • Excellent english language skills
Personal characteristics
  • innovative spirit and extraordinary motivation, interest in purposeful work
  • team work orientated
  • organized, ability for analytic and independent work ethic

If you're the right person: please send all application documents, e.g. cover letter, curriculum vitae, certificates, attestations, etc. to the following address, quoting the reference number by e-mail to
Charité – Universitätsmedizin Berlin
Chirurgische Klinik, Exp. Chirurgie
z.Hd. PD Dr. Nathanael Raschzok
Augustenburger Platz 1
D-13353 Berlin
nathanael.raschzok@charite.de
Extended liver resection in mice: state of the art and pitfalls
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"Extended liver resection in mice: state of the art and pitfalls – a systematic review" is available in ur J Med Res. 2021; 26(1):6.
Rodent models of liver resection have been used to investigate and evaluate the liver's complex physiology and pathology since 1931. First documented by Higgins and Anderson, such models were created to understand liver regeneration mechanisms to improve outcomes in patients undergoing extensive liver resection for liver cancer or other underlying liver diseases. A systematic search was conducted using Pubmed, gathering publications up to January 2019, which engaged with the mouse model of extended liver resection as a method itself. The results of this search were filtered according to their language, novelty, and relevancy.
Through the overview, laid out in the selected publications, this paper reviews the shift of the extended liver resection model from rat to the mouse, describes the state of the art in the experimental setting, and discusses the possible limitations and pitfalls. Clearly, the extended liver resection in mice is a reproducible, practical and easy to learn method.
Authors are Can Kamali, Kaan Kamali, Philipp Brunnbauer, Katrin Splith, Johann Pratschke, Moritz Schmelzle, and Felix Krenzien.
Two new (Junior) Clinician Scientitsts
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Dr. Simon Moosburner and Dr. Tomasz Dziodzio successfully applied for the BIH Charité (Junior) Clinician Scientist Program.

Dr. Dziodzio is studying pathomechanisms of obesity in the context of kidney transplantation and investigates the impact of obesity on the immune response in the kidney transplant recipient. In addition, a clinical trial will investigate whether surgical weight reduction in obese patients prior to kidney transplantation leads to improved graft function.

Dr. Moosburner is working on the extracorporeal evaluation of liver grafts from older donors. The aim is to characterise old liver grafts during normothermic machine perfusion. For this purpose, a model for normothermic ex vivo machine perfusion of small animal livers as well as liver transplantation in the rat model was established.

Best Poster prize for Anna Pfefferkorn
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Anna Pfefferkorn won the Best Poster prize for our work on "Molecular and cellular mechanisms of Lipocalin-2 mediated renoprotection in kidney transplantation" at the Kongress für Nephrologie 2020, held in Berlin 1.-4. October, 2020!

Lipocalin-2 (Lcn2) is distinctly upregulated in kidney transplants and serves as an early marker of AKI, DGF and acute rejection. However, the functional role and mechanisms underlying Lcn2 upregulation remain largely unknown. Using a mouse model of kidney transplantation we recently demonstrated a renoprotective role of recombinant Lcn2:Siderophore:Fe (rLcn2). However, the molecular and cellular events underlying the renoprotective effects of rLcn2 in kidney allografts remain unclear. Elucidating these events forms the primary focus of the current study.
rLcn2 significantly lowered CD8+ T cells in the allograft, LN and blood at POD 7, whereas their number remained unaffected in spleen. Nevertheless, the number of CD4+ T Lymphocytes was reduced only in lymph nodes. NKG2D+CD8+T cells and CD27+CD11b+NKp46+NK cells were the most prominent subpopulations of the cytotoxic lymphocytes whose frequencies were significantly reduced in graft, spleen and blood with the treatment of rLcn2. Besides, a significantly reduced infiltration of monocytes/macrophages was also observed at POD-7 with the said treatment. Importantly, degranulation capacity and IFNg production of intragraft and splenic CD4+ and CD8+ T cells were impaired in the treated animals. Besides, rLcn2 lowered hypoxia and reoxygenation induced cytotoxicity of the primary RTECs, associated with reduced caspase-3 cleavage and activation of Erk and AKt signaling.

rLcn2 treatments differentially affects the relative frequencies and activation of various immune cell. Besides, rLcn2 depicts cytoprotective effect on murine primary RTECs during H/R, possibly via activation of Erk and Akt signaling.

CONGRATULATIONS !
Dual versus single vessel normothermic ex vivo perfusion of rat liver grafts using metamizole for vasodilatation
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F. Claussen, J.M.G.V. Gassner, S. Moosburner, D. Wyrwal, M. Nösser, P. Tang, L. Wegener, J. Pohl, A. Reutzel-Selke, R. Arsenic, J. Pratschke, I.M. Sauer, and N. Raschzok published their trecent work on "Dual versus single vessel normothermic ex vivo perfusion of rat liver grafts using metamizole for vasodilatation" in PLoS One 2020;15(7): e0235635.

Normothermic ex vivo liver perfusion (NEVLP) is a promising strategy to increase the donor pool in liver transplantation. Small animal models are essential to further investigate questions regarding organ preservation and reconditioning by NEVLP. A dual vessel small animal NEVLP (dNEVLP) model was developed using metamizole as a vasodilator and compared to conventional portovenous single vessel NEVLP (sNEVLP).

Livers of male Wistar rats were perfused with erythrocyte-supplemented culture medium for six hours by either dNEVLP via hepatic artery and portal vein or portovenous sNEVLP. dNEVLP was performed either with or without metamizole treatment. Perfusion pressure and flow rates were constantly monitored. Transaminase levels were determined in the perfusate at the start and after three and six hours of perfusion. Bile secretion was monitored and bile LDH and GGT levels were measured hourly. Histopathological analysis was performed using liver and bile duct tissue samples after perfusion.

Hepatic artery pressure was significantly lower in dNEVLP with metamizole administration. Compared to sNEVLP, dNEVLP with metamizole treatment showed higher bile production, lower levels of transaminases during and after perfusion as well as significantly lower necrosis in liver and bile duct tissue. Biochemical markers of bile duct injury showed the same trend.

Our miniaturized dNEVLP system enables normothermic dual vessel rat liver perfusion. The administration of metamizole effectively ameliorates arterial vasospasm allowing for six hours of dNEVLP, with superior outcome compared to sNEVLP.

Simon Moosburner defended thesis summa cum laude
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Today, Simon Moosburner successfully defended his doctoral thesis entitled "Erweiterung der Spenderpopulation bei Lebertransplantation: Klinischer Bedarf und Entwicklung eines Kleintier-Lebermaschinenperfusionssystems (Expanding the donor pool for liver transplantation: clinical need and development of small animal liver perfusion system)" summa cum laude !

Congratulations!
Einstein BIH Visiting Fellow project, funded by Stiftung Charité
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The Stiftung Charité will fund our project “Vascular Composite Tissue Allotransplantation (VCA): An integrated, multidisciplinary basic and clinical research program for hand and uterus transplantation” (Einstein BIH Visiting Fellowship) within the framework of the Private Excellence Initiative Johanna Quandt for two more years!

The Charité has a long tradition as an international leader in transplantation. Prior to starting our Einstein BIH funded project in February 2017, Vascular Composite Tissue Allotransplantation (VCA) was neither object of scientific investigations, nor offered to patients. As an Einstein BIH Visiting Fellow Prof. Stefan G. Tullius, Harvard Medical School, ignited both: a basic research group in this field and a clinical research transplant program. During the first three years of our multidisciplinary basic and clinical research program, we have been able to implement complex small animal models (mouse hindlimb, heart, skin transplant models); a rat uterus transplant model is currently established. Those models offer unique opportunities to address basic research questions of translational relevance including: organ-specific alloimmune responses, immunogenicity, and the maternal-fetal interface in uterus transplantation.
An enthusiast clinical, multi-disciplinary has been established, led and mentored by Prof. Tullius that has brought preparatory surgical exercises and clinical algorithms for VCA at the Charité on the way.

Stiftung Charité is an independent charitable foundation. It was endowed in 2005 by entrepreneur Johanna Quandt, who entrusted it with the mission of supporting the innovative potential and excellence of Berlin’s university medicine, which can look back on a rich tradition in medical research and patient care. Thereby, the foundation is active in two focal areas: promoting technology transfer between the laboratory and the clinic as well as improving the framework conditions for innovation and entrepreneurship in medicine. Since 2014, Stiftung Charité is also funding the life sciences in Berlin by its Private Excellence Initiative Johanna Quandt.
EUROSTARS project
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Within the Eurostars project „Comprehensive qualitative/quantitative multi-pathogen IVD workflow for immunocompromised patients (Im-compr-IVD)“ an IVD workflow covering sample preparation up to clinical relevant diagnosis of infection in immunocompromised patients will be developed. Deliverables are:
  • Design, development and preclinical validation of QIC-Finder assay with novel primers and probes for qualitative and quantitative screening of 23 pathogens (bacterial, viral, fungal and parasitic);
  • Detection instrumentation and interpretation software optimized for assay performance;
  • Instructions for high quality DNA/RNA extraction from plasma.
Partners are Pathofinder (Netherlands, Coordinator), Ella Biotech (Germany), IT-IS International Ltd. (United Kingdom) and Charité - Universitätsmedizin Berlin.

Eurostars projects are co-funded by EUREKA member countries and the European Union Horizon 2020 Framework program.
DFG Research Grant
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Priv.-Doz. Dr. Nathanael Raschzok receives a research grant from the Deutsche Forschungsgemeinschaft (DFG) for his project "Defatting of steatotic liver grafts by normothermic ex vivo machine perfusion with DNP" in collaboration with Prof. Dr. med. Andreas Birkenfeld, Universitätsklinikum Carl Gustav Carus, Dresden.

Transplantation of steatotic marginal liver grafts is associated with a certain risk of graft dysfunction, primary non-function, and biliary complications, which results in a worse outcome compared to transplantation of unimpaired livers.
We hypothesize, that normothermic machine perfusion combined with adequate pharmacological intervention can prevent the deleterious effect of ischemia-reperfusion injury on macrovesicular grafts by a) minimizing the negative effect of cold storage, and by b) actively decreasing the intracellular fat content of the graft.
Mild mitochondrial uncoupling by DNP decreases the intrahepatic fat content of steatotic liver grafts during normothermic ex vivo machine perfusion. Efficient defatting can be safely achieved ex vivo with DNP concentrations that would be toxic in vivo. Systemic side effects of DNP are prevented by exclusive hepatic exposure through machine perfusion, and by washing DNP out of the liver graft at the end of the perfusion period. The synergetic effects of normothermic perfusion and defatting with DNP will prevent ischemia-reperfusion injury and make severely steatotic liver grafts acceptable for transplantation.
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SFB 1365 Renoprotection
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The Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) is establishing ten new Collaborative Research Centres (CRCs, Sonderforschungsbereich, SFB) to further support top-level research in Germany.
Chronic kidney diseases and acute kidney damage are widespread and reduce the life expectancy of those affected. The CRC “Renoprotection” therefore aims to decode specific signalling pathways for kidney damage and develop new approaches to treatment in the long term (Charité Berlin – FU Berlin and HU Berlin, Spokesperson: Prof. Dr. Pontus Börje Persson).
With the project "Renoprotective role of Lipocalin-2 in allograft rejection following kidney transplantation" Priv.-Doz. Dr. Felix Aigner and Dr. Muhammad Imtiaz Ashraf, PhD will be part of this SFB/CRC!

To provide allograft renoprotection, novel strategies are needed, including (i) prevention of renal allograft IRI and (ii) targeted immunosuppression and thus; reduction and avoidance of steroid and CNI usage in the long-run. Using a mouse model of kidney transplantation, we recently demonstrated a renoprotective role of exogenously administered recombinant Lcn2:Siderophore:Fe complex (rLcn2). The rLcn2 mediated mechanism of allograft renoprotection is still unknown; however, the mechanistic insight is essential for comprehensive translation of the rLcn2 therapy into clinical practice. In the funded project, we aim at (i) understanding the route and mechanisms of immunoregulation and/or cytoprotection, mediated by exogenously administered rLcn2 during the allograft damage; and (ii) characterizing the source and nature of endogenous Lcn2 i.e. whether it is complexed with mammalian iron binding catechols and may contribute to allograft survival in the long-run. Our ultimate goal is to pave the way for transplant renoprotection via recombinant Lcn2.

More information…
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Mathilde Feist and Paul Ritschl: Clinician Scientists
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Dr. Mathilde Feist and Dr. Paul Ritschl successfully applied for the BIH Charité Clinician Scientist Program. Mathilde Feist will work on "Cytokine-armed oncolytic vaccinia virus for pancreatic cancer therapy". Mentors are Prof. Bahra, Prof. Sauer and Prof. Beling.
Paul Ritschl focusses on "The Impact of Donor Derived Microparticles Following Solid Organ Transplantation". Mentors are Priv.-Doz. Dr. Schmelzle and Priv.-Doz Dr. Öllinger.
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Hendrik Napierala defended his thesis summa cum laude
Today, Hendrik Napierala defended his thesis "Rebesiedlung dezellularisierter Rattenpankreata mit Langerhans-Inseln" summa cum laude!

Congratulations !
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Wibke Schulte: BIH Charité Clinician Scientist
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Dr. med. Wibke Schulte successfully applied for the BIH Charité Clinician Scientist Program with her project „Die Rolle von MIF in der humanen akuten Peritonitis | Role of MIF in human acute peritonitis“. Mentors are Priv.-Doz. Dr. med. Felix Aigner and Prof. Dr. Igor M. Sauer.
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Barbara Kern: BIH Charité Clinician Scientist
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Dr. Barbara Kern successfully applied for the BIH Charité Clinician Scientist Program. With her project "Novel Treatment and Diagnostic Approaches Utilizing the Role of Dendritic Cells in Immune Responsivness" Barbara will be engaged in our Vascular Tissue Allotransplantation Initiative (Project VCA). The Clinician Scientist Program is a modern career pathway within academic medicine that allows physicians to pursue a structured residency with time set aside for clinical and basic research. At the end of the program, participants will have completed their residency and, ideally, their postdoctoral teaching qualification (Habilitation). The program is intended to produce a new generation of scientists with translational training who will help speed up the rate at which scientific findings are translated into application.
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ESOT The Future of Transplantation
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The ESOT YPT Workshop and its Presidential Debate gives you a chance to engage with a variety of speakers in a lively ‘town hall’ format, as well as connecting with other young transplant professionals from around the world. The session will begin with talks from three key presenters on the past, present, and future of transplantation and open Q&As with each presenter. 

09:00– 10:35 - The future of transplantation: 3 lectures on Past, Present and Future CHAIRS: Alice Koenig, Lyon, France   Thomas Resch, Innsbruck, Austria
09:05 Lecture: The future of transplantation - Historical Perspective Sir Roy Calne, Cambridge, United Kingdom 09:25 Open Q&A with Roy Calne
09:35 Lecture: The future of transplantation - Present perspective Jan Lerut, Brussels, Belgium 09:55 Open Q&A with Jan Lerut
10:05 Lecture: The future of transplantation - Future perspective  Igor Sauer, Berlin, Germany
10:25 Open Q&A with Igor Sauer
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Cells isolated from diseased explanted livers
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The International Journal of Artificial Organs (official journal of the European Society for Artificial Organs [ESAO]) published our paper on Isolation, characterization and cold storage of cells isolated from diseased explanted livers. Authors are Belaschk E, Rohn S, Mukiibi R, Reutzel-Selke A, Tang P, Sawitzki B, Pratschke J, Sauer IM and Mogl MT.

Livers discarded after standard organ retrieval are commonly used as a cell source for hepatocyte transplantation. Due to the scarcity of organ donors, this leads to a shortage of suitable cells for transplantation. Here, the isolation of liver cells from diseased livers removed during liver transplantation is studied and compared to the isolation of cells from liver specimens obtained during partial liver resection. Hepatocytes from 20 diseased explanted livers (Ex-group) were isolated, cultured and stored at 4°C for up to 48 hours, and compared to hepatocytes isolated from the normal liver tissue of 14 liver lobe resections (Rx-group). The nonparenchymal cell fraction (NPC) was analyzed by flow cytometry to identify potential liver progenitor cells, and OptiPrep™ (Sigma-Aldrich) density gradient centrifugation was used to enrich the progenitor cells for immediate transplantation. There were no differences in viability, cell integrity and metabolic activity in cell culture and survival after cold storage when comparing the hepatocytes from the Rx-group and the Ex-group. In some cases, the latter group showed tendencies of increased resistance to isolation and storage procedures. The NPC of the Ex-group livers contained considerably more EpCAM+ and significantly more CD90+ cells than the Rx-group. Progenitor cell enrichment was not sufficient for clinical application. Hepatocytes isolated from diseased explanted livers showed the essential characteristics of being adequate for cell transplantation. Increased numbers of liver progenitor cells can be isolated from diseased explanted livers. These results support the feasibility of using diseased explanted livers as a cell source for liver cell transplantation.
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Recellularization of rat livers: morphology and function
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The Journal of Tissue Engineering and Regenerative Medicine accepted our paper „Evolution of graft morphology and function after recellularization of decellularized rat livers“ for publication.

Decellularization of livers is a well-established procedure. Data on different reseeding techniques or the functional evolution and re-organization processes of repopulated grafts remains limited. 

We established a proprietary, customized bioreactor to repopulate decellularized rat livers (n=21) with primary rat hepatocytes (150 x 106 cells) via the hepatic artery and to subsequently evaluate graft morphology and function during seven days of ex vivo perfusion. Grafts were analyzed at 1h, 6h, 12h, 24h, 3d, 5d and 7d after recellularization (all n=3) by immunohistologic evaluation, hepatocyte-related enzyme (AST, ALT, LDH) and albumin measurement in the perfusate. 
To the best of our knowledge, this is the first available protocol for repopulation of rat livers via the hepatic artery. Within the first 24 hours after repopulation, the hepatocytes seemed to migrate out of the vascular network and form clusters in the parenchymal space around the vessels. Graft function increased for the first 24 hours after repopulation with a significantly higher function compared to standard 2D culture after 24 hours. Thereafter, graft function constantly decreased with significantly lower values after six and seven days of perfusion, although histologically viable hepatocytes were found even after this period. Our data suggests that due to a constant loss of function, repopulated grafts should potentially be implanted as soon as cell engraftment and graft re-organization are completed. 

Authors are Antje Butter, Khalid Aliyev, Karl-Herbert Hillebrandt, Nathanael Raschzok, Martin Kluge, Nicolai Seiffert, Peter Tang, Hendrik Napierala, Muhammad Imtiaz Ashraf, Anja Reutzel-Selke, Andreas Andreou, Johann Pratschke, Igor Maximilian Sauer, and Benjamin Struecker.
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