News

ECRT - Advanced Scientist Grant

14.05.2017 In: Grant written by: Prof. Dr. Igor M. Sauer

PD Dr. Nathanael Raschzok receives one of the 2017 Einstein Center for Regenerative Therapies (ECRT) Kickbox – Advanced Scientist Grant.
Einstein Center for Regenerative Therapies Kickbox – advanced scientist grant. The project is entitled „Overcoming steatotic compromise – Reconstitution of endogenous repair in severely steatotic liver grafts by metabolic reconditioning“. The project will be conducted by Nathanael Raschzok, Angelika Kusch, Duska Dragun, and Igor M. Sauer.

In order to stimulate excellent and creative research ideas that might take regenerative therapies a vital step forward, the Einstein Center offers a special two-stage funding scheme. At first, the Kickbox seed grant provides a great framework to investigate initial ideas and to develop sound research concepts. Subsequently, the flexible funds enable the realisation of projects that evolved from the Kickbox initiation phase in order to reach the scientific goals of the Einstein Center. Congratulations!

Magnetic field and cells labeled with IO particles

12.05.2017 In: Publications written by: Prof. Dr. Igor M. Sauer

Our paper entitled "The magnetic field of magnetic resonance imaging systems does not affect cells labeled with micrometer-sized iron oxide particles," has been accepted for publication in Tissue Engineering, Part C: Methods. Authors are Martin Kluge, Annekatrin Leder, Karl H. Hillebrandt, Benjamin Struecker, Dominik Geisel, Timm Denecke, Rebeka D. Major, Anja Reutzel-Selke, Peter Tang, Steffen Lippert, Christian Schmidt, Johann Pratschke, Igor M. Sauer, and Nathanael Raschzok.

Labeling using iron oxide particles enables cell tracking via magnetic resonance imaging (MRI). However, the magnetic field can affect the particle-labeled cells. Here, we investigated the effects of a clinical MRI system on primary human hepatocytes labeled using micrometer-sized iron oxide particles (MPIOs). HuH7 tumor cells were incubated with increasing concentrations of biocompatible, silica-based, micron-sized iron oxide-containing particles (sMPIO; 40 – 160 particles/cell). Primary human hepatocytes were incubated with 100 sMPIOs/cell. The particle-labeled cells and the native cells were imaged using a clinical 3.0-T MRI system, whereas the control groups of the labeled and unlabeled cells were kept at room temperature without exposure to a magnetic field. Viability, formation of reactive oxygen species, aspartate aminotransferase leakage, and urea and albumin synthesis were assessed over a culture period of 5 days.
The dose finding study showed no adverse effects of the sMPIO labeling on HuH7 cells. MRI had no adverse effects on the morphology of the sMPIO-labeled primary human hepatocytes. Imaging using the T1- and T2-weighted sequences did not affect the viability, transaminase leakage, formation of reactive oxygen species, or metabolic activity of the sMPIO-labeled cells or the unlabeled, primary human hepatocytes. sMPIOs did not induce adverse effects on the labeled cells under the conditions of the magnetic field of a clinical MRI system.

PD Dr. N. Raschzok & PD Dr. A. Andreou

08.05.2017 In: General written by: Prof. Dr. Igor M. Sauer

Charité BIH Entrepreneurship Summit

07.05.2017 In: Meetings written by: Prof. Dr. Igor M. Sauer

The Charité BIH Entrepreneurship Summit is a preeminent international cross-disciplinary forum for sharing and exploring the most important discoveries and emerging trends influencing the future of healthcare around the world.

Every year in May over 400 global leaders in healthcare innovation, including entrepreneurs, scientists, physicians, investors, policymakers, and business leaders convene at the Charité BIH Entrepreneurship Summit in the vibrant German capital of Berlin. We offer our participants a one-of-a-kind opportunity to meet with world-class specialists working at Charité & MDC, to build relationships with prominent international partners and experts working in the healthcare industry, and to help grow businesses.

This year's 10th Charité Entrepreneurship Summit will again take place at the Berlin-Brandenburg Academy of Sciences and Humanities on May 8 - 9, 2017. The Summit is significantly supported by the Berlin Institute of Health and focusses on 'Global Challenges of Healthcare'. Israel will be the official partner country for the Summit 2017. We are looking forward to learning more about the Israeli innovation & start-up culture, funding opportunities and challenges in Healthcare.

The Summit's two-day agenda will address a wide variety of topical issues including change of innovation culture, healthy aging & degenerative diseases, virtual reality and mental health. In addition, the Summit will seek to engage participants in lively discussions about business, science and the intersection of the two. Startups and Entrepreneurs are invited to apply for the LifeSciences VentureMarket, a platform to present their companies to a pool of international angels, venture investors, and corporate funds at this year's Summit.

BIH Paper of the Month

05.05.2017 In: Publications written by: Prof. Dr. Igor M. Sauer

Benjamin Strücker, Hendrik Napierala and the rest of the team were awarded with the BIH Paper of the Month for their publication on a new method for developing a transplantable endocrine Neo-Pancreas.

The BIH Paper of the Month is awarded by the BIH Board of Directors to honor a special publication achievement from the joint research space of Charité and MDC. The Paper of the Month is sponsored by the Stiftung Charité as part of its Johanna Quandt Private Excellence Initiative.

H. Napierala, K.-H. Hillebrandt, N. Haep, P. Tang, M. Tintemann, J. Gassner, M. Noesser, H. Everwien, N. Seiffert, M. Kluge, E. Teegen, D. Polenz, S. Lippert, D. Geisel, A. Reutzel Selke, N. Raschzok, A. Andreou, J. Pratschke, I. M. Sauer & B. Struecker. Engineering an endocrine Neo-Pancreas by repopulation of a decellularized rat pancreas with islets of Langerhans. Scientific Reports 7. Article number: 41777 (2017) doi:10.1038/srep41777

Dr. Karl

08.04.2017 In: General written by: Prof. Dr. Igor M. Sauer

ECRT Kickbox - Junior Scientist Grant

07.05.2017 In: Grant written by: Prof. Dr. Igor M. Sauer

Karl Hillebrandt receives one of the 2017 Einstein Center for Regenerative Therapies (ECRT) Kickbox – Junior Scientist Grant. The project is entitled "Fighting liver cirrhosis? Establishment and analysis of decellularized human cirrhotic liver slices as a 3-dimensional model to study cell matrix interactions".

Liver cirrhosis is one of the main indications for liver transplantation. Due to the organ shortage, this therapy option is limited to the minority of patients suffering from cirrhosis. Therefore, there is a need of alternative treatment options.The aim of our project is to establish a decellularization protocol for human cirrhotic livers slices, which preserves the natural extracellular matrix (ECM) of cirrhotic livers. These decellularized liver slices will serve as a 3 dimensional model to study cell matrix interactions. If we are able to establish a protocol which will preserve the ECM, we will conduct in vitro recellularization experiments to study how the cirrhotic ECM will change the genotype and phenotype of different cell types. With this knowledge we aim to modify specific cell types in vivo or vitro for example prior to cell transplantation. Our ambition is to steer the cell matrix interaction via these modified cells after their transplantation and thereby halt or even reverse the progress of liver cirrhosis. This approach may offer an alternative treatment option in the future.

Team : Karl Hillebrandt, Oliver Klein, Ben Strücker, Igor Sauer

imag|Ne surgery – April 28-29, 2017

02.04.2017 In: Meetings written by: Prof. Dr. Igor M. Sauer

Einstein Center Digital Future – Opening

29.03.2017 In: Meetings written by: Prof. Dr. Igor M. Sauer

Einstein Visiting Fellow Prof. Stefan G. Tullius

24.02.2017 In: General written by: Prof. Dr. Igor M. Sauer

Prof. Dr. Stefan G. Tullius, Harvard Medical School, became Einstein BIH Visiting Fellow at the Charité, Department of Surgery.

Vascular Composite Tissue Allotransplantation (VCA) has developed from a pioneering endevour to a clinical reality during the last 15 years. More than 150 extremity, face, knee, and most recently uterus and penis transplants have been performed during the last 15 years. VCA activities have been seen around the globe. Although feasibility of the procedure has been shown, it is still emerging and far from being a standard clinical procedure.

The Charité has been an international leader in transplantation research for decades. However, neither VCA basic clinical research programs are currently offered in Berlin or Germany in a meaningful way.The involvement of Prof. Tullius as an Einstein BIH Visiting Fellow is expected to synergize and accelerate efforts igniting both a clinical research transplant program and a basic research group of excellence. The overall objective of our integrated basic and clinical research working group Vascular Composite Tissue Transplantation has three main goals:

To establish a basic Research group of Excellence: VCAs offer unique opportunities to study novel aspects of antigenicity, immune modulation and neo-vascularization. One important aspect that distinguishes VCA from solid organ transplants is their blood supply through a vascularized arterial in- and venous outflow in addition to sprouting new vessels at the large interface of VCA with recipient tissue.

To establish a clinical bio-repository as a pre-requisite for a clinical research VCA program.

To implement a clinical VCA research program (hand, abdominal wall, uterus) as a multi- disciplinary and translational effort.

Transplantation in Transition

01.02.2017 In: Meetings written by: Prof. Dr. Igor M. Sauer

Foschungs-Colloquium 2017 - Impressions

10.01.2017 In: Meetings |Presentations written by: Prof. Dr. Igor M. Sauer

Engineering an endocrine Neo-Pancreas

02.01.2017 In: Publications written by: Prof. Dr. Igor M. Sauer

Scientific Reports accepted our latest paper on „Engineering an endocrine Neo-Pancreas by repopulation of a decellularized rat pancreas with islets of Langerhans“. Authors are H. Napierala, K. Hillebrandt, N. Haep, P. Tang, M. Tintemann, J. Gassner, M. Noesser, H. Everwien, N. Seiffert, M. Kluge, E. Teegen, D. Polenz, S. Lippert, D. Geisel, A. Reutzel-Selke, N. Raschzok, A. Andreou, J. Pratschke, I.M. Sauer, and B. Struecker.
Decellularization of pancreata and repopulation of these non-immunogenic matrices with islets and endothelial cells could provide transplantable, endocrine Neo- Pancreata. In this study, rat pancreata were perfusion decellularized and repopulated with intact islets, comparing three perfusion routes (Artery, Portal Vein, Pancreatic Duct). Decellularization effectively removed all cellular components but conserved the pancreas specific extracellular matrix. Digital subtraction angiography of the matrices showed a conserved integrity of the decellularized vascular system but a contrast emersion into the parenchyma via the decellularized pancreatic duct. Islets infused via the pancreatic duct leaked from the ductular system into the peri-ductular decellularized space despite their magnitude. TUNEL staining and Glucose stimulated insulin secretion revealed that islets were viable and functional after the process.
We present the first available protocol for perfusion decellularization of rat pancreata via three different perfusion routes. Furthermore, we provide first proof-of-concept for the repopulation of the decellularized rat pancreata with functional islets of Langerhans. The presented technique can serve as a bioengineering platform to generate implantable and functional endocrine Neo-Pancreata.

Forschungscolloquium 2017 Program

02.01.2017 In: Meetings written by: Prof. Dr. Igor M. Sauer

Recellularization of rat livers: morphology and function

02.01.2017 In: Publications written by: Prof. Dr. Igor M. Sauer

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.

Neujahrsessen 2017

02.12.2016 In: General written by: Prof. Dr. Igor M. Sauer

Visit of Jean-Philippe Courtois and Renate Radon

30.11.2016 In: Projects written by: Prof. Dr. Igor M. Sauer

Vascular anatomy of the juvenile Göttingen minipig

30.11.2016 In: Publications written by: Prof. Dr. Igor M. Sauer

Lab Animal accepted our „Computed tomography-based survey of the vascular anatomy of the juvenile Göttingen minipig“ for publication.

Over the past 50 years, image-guided procedures have been established for a wide range of applications. The development and clinical translation of new treatment regimens necessitate the availability of suitable animal models. The juvenile Göttingen minipig presents a favourable profile as a model for human infants. However, no information can be found regarding the vascular system of juvenile minipigs in the literature. Such information is imperative for planning the accessibility of target structures by catheterization.

We present here a complete mapping of the arterial system of the juvenile minipig based on contrast-enhanced computed tomography. Four female animals weighing 6.13 ± 0.72 kg were used for the analyses. Imaging was performed under anaesthesia, and the measurement of the vascular structures was performed independently by four investigators. Our dataset forms a basis for future interventional studies in juvenile minipigs, and enables planning and refinement of future experiments according to the 3R (replacement, reduction and refinement) principles of animal research.

Authors are J. Siefert, K.H. Hillebrandt, M. Kluge, D. Geisel, P. Podrabsky, T. Denecke, M. Nösser, J. Gassner, A. Reutzel-Selke, B. Strücker, M.H. Morgul, S. Guel-Klein, J.K. Unger, A. Reske, J. Pratschke, I.M. Sauer, and N. Raschzok.

Monitoring of hepatocyte transplantation by MRI

17.10.2016 In: Publications written by: Prof. Dr. Igor M. Sauer

A new book on Hepatocyte Transplantation Methods and Protocols, part of the series: Methods in Molecular Biology, Vol. 1506 P. Stock, B. Christ (Eds.), Springer, will be available end of November, 2016. We contributed a chapter on Preclinical swine models for monitoring of hepatocyte transplantation by MRI (authors: Nathanael Raschzok, Ulf Teichgräber, Johann Pratschke, and Igor M. Sauer) and are proud to provide the cover image.

This volume features up-to-date protocols for the isolation, preservation, and validation of various cell sources comprising large and small animal models, examining the impact of cell transplantation on acute and chronic liver diseases. Hepatocyte Transplantation: Methods and Protocols guides readers through laboratory protocols for the generation of humanized livers for the assessment of biological actions in vivo and techniques to monitor cell engraftment after cell transplantation in vivo are described and procedures for computational analyses of hepatocyte transplantation.

Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Comprehensive and practical, Hepatocyte Transplantation: Methods and Protocols is an essential resource for researchers and clinicians to assess the biological as well as the therapeutic potential of hepatocyte transplantation.

Staatsexamen

14.10.2016 In: General written by: Prof. Dr. Igor M. Sauer

More than 100 days of loops of learning and 3 days conquering more than 300 questions: 5 faces. Congratulations! We are all looking forward to having you back in the lab!

HCC: miRNA profiles of the tumor-surrounding tissue

08.09.2016 In: Publications written by: Prof. Dr. Igor M. Sauer

The presence of hepatocellular carcinoma (HCC) is a significant complication of cirrhosis because it changes the prognosis and the treatment of the patients. By now, contrast-enhanced CT and MR scans are the most reliable tools for the diagnosis of HCC; however, in some cases, a biopsy of the tumor is necessary for the final diagnosis. The aim of the study was to develop a diagnostic tool using the microRNA (miRNA) profiles of the tissue surrounding the HCC tumor combined with clinical parameters in statistical models. At a transplantation setting, 32 patients with HCC and cirrhosis (B) were compared to 22 patients suffering from cirrhosis only (A). The diagnosis and exclusion of HCC was confirmed following the histopathological examination of the explanted liver.

The HCC patients were significantly older than the patients with cirrhosis only (B: 60.6 and A: 49.9, p<0.001) and showed higher levels of ALT (A: 0.76μkat/l, B: 1.02μkat/, p=0.006) and AFP (A: 5.8ng/ml, B: 70.3ng/ml, p<0.001), whereas the bilirubin levels were higher in the cirrhosis only group (p=0.002). Using age (cut-off 50.23years) and AFP (cut-off 4.2ng/ml) thresholds, the levels of expression of miR-1285-3p and miR-943 differentiated between the patients with HCC and cirrhosis from those with cirrhosis only with an accuracy of 96.3%. This is the first report about the use of stepwise penalized logistic regression and decision tree analyses of miRNA expressions in the tumor-surrounding tissue combined with clinical parameters for the diagnosis of HCC.

Authors are Mehmet Haluk Morgul, Sergej Klunk, Zografia Anastasiadou, Ulrich Gauger, Corinna Dietel, Anja Reutzel-Selke, Philipp Felgendref, Hans-Michael Hau, Hans-Michael Tautenhahn, Rosa Bianca Schmuck, Nathanael Raschzok, Igor Maximillian Sauer, and Michael Bartels. Exp Mol Pathol. 2016 Aug 20;101(2):165-171. doi: 10.1016/j.yexmp.2016.07.014. [Epub ahead of print]

Tags: miRNA

Bile: miRNA Pattern post OLT

03.08.2016 In: Publications written by: Prof. Dr. Igor M. Sauer

BIOMARKERS accepted our latest paper on "Bile: miRNA Pattern and Protein Based Biomarkers May Predict Acute Cellular Rejection after Liver Transplantation" for publication. Authors are Rosa Bianca Schmuck, Anja Reutzel-Selke, Nathanael Raschzok, Mehmet Haluk Morgul, Benjamin Struecker, Steffen Lippert, Cynthia de Carvalho Fischer, Moritz Schmelzle, Sabine Boas-Knoop, Marcus Bahra, Andreas Pascher, Johann Pratschke, and Igor M. Sauer.

Bile rather than blood depicts the local inflammation in the liver and may improve prediction and diagnosis of acute cellular rejection (ACR) after liver transplantation (OLT). Secretome and miRNAs were analyzed during the first two weeks and on clinical suspicion of ACR in the bile of 45 OLT recipients. Levels of CD44, CXCL9, miR-122, miR-133a, miR-148a and miR-194 were significantly higher in bile of patients who developed ACR within the first 6 months after OLT and during ACR. Analysis of secretome and miRNA in bile could further our understanding of the local inflammatory process during rejection.

Hepatocyte isolation after laparoscopic liver resection

12.07.2016 In: Publications written by: Prof. Dr. Igor M. Sauer

Tissue Engineering, Part C: Methods accepted our paper entitled "Hepatocyte isolation after laparoscopic liver resection" for publication. Authors are Horner R*, Kluge M*, Gassner J, Nösser M, Major RD, Reutzel-Selke A, Leder AK, Struecker B, Morgul MH, Pratschke J, Sauer IM, Raschzok N (*contributed equally).

Liver tissue obtained from partial hepatectomy is a common source for isolation of primary human hepatocytes. Until now, liver resections were most commonly performed by conventional open surgery. Although the laparoscopic approach is currently emerging in liver surgery, data on the outcome of hepatocyte isolation from laparoscopically resected liver tissue is not available. A total of 22 hepatocyte isolations were performed using the two-step collagenase perfusion technique from October 2015 until March 2016. Liver tissue was obtained from n=15 open liver resections (OLR) and n=7 laparoscopic liver resections (LLR). Isolation parameters (cell yield, viability, percoll survival) were assessed and hepatocyte function (plating efficiency, urea, albumin, and aspartate aminotransferase) was measured over a culture period of 6 days (OLR: n=13; LLR: n=3). Total cell yield (OLR: 36.81 ± 6.77 x106 cells/g vs. LLR 16.84 ± 10.66 x106 cells/g, p=0.0318) as well as viable yield (OLR 31.70 ± 6.05 x106 cells/g vs. LLL 14.70 ± 9.89 x106 cells/g, p=0.0260) were significantly higher in the OLR group. Subgroup analysis revealed that the worse outcome of isolation of laparoscopically resected liver tissue was associated with right-lateral laparoscopic liver resections, while hepatocyte isolation from left-lateral laparoscopic liver resections was as effective as from open surgery. Hepatocyte function did not differ between hepatocytes from openly resected versus left-lateral laparoscopically resected liver tissue. We here present the first data on hepatocyte isolation from laparoscopic liver surgery. While the overall outcome is worse compared to open surgery, our data suggest that liver tissue from laparoscopic resection of the left lobe is an excellent source for primary human hepatocytes.

Tags: Hepatocyte Isolation,Liver

Five years BIH Charité Clinician Scientist Program

04.07.2016 In: General written by: Prof. Dr. Igor M. Sauer

Tags: Clinican Scientist Program

BIH Charité Clinician Scientist Symposium

17.06.2016 In: Meetings written by: Prof. Dr. Igor M. Sauer

SPARK Berlin supports Fikatas Knot

29.04.2016 In: Projects |Grant |Surgical Techniques written by: Prof. Dr. Igor M. Sauer

The Berlin Institute of Health (BIH) and Stiftung Charité teamed up with Stanford University School of Medicine to initiate SPARK Berlin.

We are very pleased to announce that Dr. Panagiotis Fikatas' project “Device for ready-prepared surgical knots” was selected for both, funding and mentorship.

SPARK was created to overcome the hurdles associated with translating academic discoveries into therapeutics and diagnostics that address unmet medical needs. The SPARK mission is to help academics overcome the obstacles involved in moving their early discoveries from bench to bedside, to educate faculty, postdoctoral fellows and graduate students on the translational research process and path to clinical application, so that development of promising discoveries becomes second nature to our institution, and to develop more cost-effective and innovative approaches to drug development .

Congratulations!

Tags: Surgical Techniques

Ethicon Zukunfts-Award 2016

29.04.2016 In: Award written by: Prof. Dr. Igor M. Sauer

During the 133. Meeting of the Deutsche Gesellschaft für Chirurgie Dr. Panagiotis Fikatas was awarded with the Ethicon Zukunfts-Award 2016 (2nd place) – Congratulations!

Tags: Surgical Techniques

International Medical Tournament 2016

26.04.2016 In: Award written by: Prof. Dr. Igor M. Sauer

Karl Hillebrandt and his team won this year's International Medical Tournament (English League) in Novosibirsk, Russia!
Congratulations!

The International Medical Tournament is a team competition for future doctors, which provides unique professional experience such as solving complex diagnostic cases from real clinical practice without any risks, presentation and discussion of solutions among students and experts. The main goal of the competition is to help medical students gather and develop lacking skills for future medical practice, critical thinking in diagnostic process, abilities of teamwork, presentation and rhetorical skills.

NeoHybrid liver graft – proof of concept

31.03.2016 In: Publications written by: Prof. Dr. Igor M. Sauer

Cells Tissues Organs accepted our latest paper on "Allogeneic liver transplantation and subsequent syngeneic hepatocyte transplantation in a rat model – proof of concept for in vivo tissue engineering" for publication.

Authors are Susanne Rohn, Jan Schroeder, Henriette Riedel, Dietrich Polenz, Katarina Stanko, Anja Reutzel-Selke, Peter Tang, Lydia Brusendorf, Nathanael Raschzok, Peter Neuhaus, Johann Pratschke, Birgit Sawitzki, Igor M. Sauer, and Martina T. Mogl.

Aim of the project was the evaluation of a new concept for in vivo tissue engineering using autologous primary human hepatocytes and hepatic progenitor cells isolated from diseased livers explanted during orthotopic liver transplantation (LTx). Cells will be isolated and infused into the spleen for repopulation of the allogeneic liver graft. The latter is serving as biological matrix for the engraftment of autologous cells. Once these cells have engrafted, it is assumed that autologous cells will repopulate the allogeneic liver, since they should have a selective advantage due to their autologous origin. It is postulated that this will lead to a neo-hybrid liver graft, reducing immunogenicity and inducing immunoregulation thus minimizing the need for extensive immunosuppression and eventually inducing operational tolerance.

We therefore developed a new rat model for combined liver and liver cell transplantation under stable immunosuppression. Immunohistochemistry demonstrated the engraftment of transplanted cells, as confirmed by fluorescence in-situ hybridization, showing repopulation of the liver graft with 15.6 % male cells (± 1.8 SEM) at day 90. The quantitative PCR revealed 14.15 % (mean ± 5.09 SEM) male DNA at day 90. Engraftment of transplanted autologous cells after combined liver and cell transplantation was achieved for up to 90 days under immunosuppression. Immunohistochemistry indicated cell proliferation, and the fluorescence in-situ hybridization results were partly confirmed by quantitative RT-PCR. This new protocol in rats appears feasible to address long-term function and eventually induction of operational tolerance in the future.

LTx – microRNA signatures in peripheral blood ?

16.03.2016 In: Publications written by: Prof. Dr. Igor M. Sauer

BIOMARKERS accepted our latest paper on „microRNA signatures in peripheral blood fail to detect acute cellular rejection after liver transplantation“ for publication. Authors are N. Raschzok, A. Reutzel-Selke, R. Schmuck, L. Tannus, M. Morgul, C. Dietel, A. Leder, B. Struecker, S. Lippert, H. Sallmon, M. Schmelzle, M. Bartels, S. Jonas, J. Pratschke, and I.M. Sauer.

We investigated whether microRNA signatures in whole blood samples are associated with acute cellular rejection (ACR) after liver transplantation. Blood samples were collected using Paxgene technology and analyzed by microarrays and qRT-PCR. microRNA signatures failed to distinguish between 19 patients with ACR and 16 controls. Let-7b-5p and let-7c were up-regulated in a subgroup of patients with ACR during the 6th and 7th postoperative day but failed in an independent validation of 20 patients. microRNA signatures in whole blood processed by Paxgene technology are not suited for detection of ACR after liver transplantation.

Tags: miRNA,Liver Transplantation,Liver

Single Pass Albumin Dialysis – Dose finding study

04.02.2016 In: Publications written by: Prof. Dr. Igor M. Sauer

Artificial Organs accepted our paper „Single Pass Albumin Dialysis (SPAD) – A dose finding study to define optimal albumin concentration and dialysate flow“ for publication. Authors are R.B. Schmuck, G.-H. Nawrot, P. Fikatas, A. Reutzel-Selke, J. Pratschke, and I.M. Sauer.

Aim of these studies was to define the optimal conditions for SPAD in a standardized experimental set-up. Albumin concentration was adjusted to either 1%, 2%, 3%, or 4%, while the flow rate of the dialysate was kept constant at a speed of 700 ml/h. The flow rate of the dialysate was altered between 350, 500, 700, and 1000 ml/h, whereas the albumin concentration was continuously kept at 3%.

This study revealed that the detoxification of albumin bound substances could be improved by increasing the concentration of albumin in the dialysate with an optimum at 3%. A further increase of the albumin concentration to 4% did not lead to a significant increase in detoxification. Furthermore, we observed a gradual increase of the detoxification efficiency for albumin bound substances, from 350 ml/h to 700 ml/h (for bilirubin) or 1000 ml/h (for bile acids) of dialysate flow. Water-soluble toxins (ammonia, creatinine, urea, uric acid) were removed almost completely, regardless of albumin concentration or flow rate.

...

25.01.2016 In: Projects |Other written by: Prof. Dr. Igor M. Sauer

Although we do hate Facebook, feel kind of robbed and dislike the music – We have to admit: 7,201,027 clicks (as of January 25th, 2016) are impressive…

To the Video

Feature in Berliner Zeitung on Tissue Engineering

16.01.2016 In: Press written by: Prof. Dr. Igor M. Sauer

Recellularized liver created in our lab featured in the Berliner Zeitung.

ESOT | YPT – Interview with Karl Hillebrandt

07.01.2016 In: Award written by: Prof. Dr. Igor M. Sauer

Being the winner of the Rising Stars Video Session organised by the YPT Committee at the ESOT2015 Brussels Congress Karl Hillebrandt gave an interview for the ESOT | YPT webpage.

His abstract "Optimized decellularization of rat livers byarterial and portal venous perfusion underoscillating pressure conditions" and the accompanying video were the most voted at the Rising Stars Session, where the audience voted live for the best video abstract. You can read Karl's abstract in the special ESOT2015 issue of Transplant International.

Evaluation of a new knotting concept – Fikatas knot

12.12.2015 In: Projects written by: Prof. Dr. Igor M. Sauer

To the Video

Tags: Future|Lab,Surgical Techniqes

Implantation of a Neo Bile Duct in domestic pigs

19.10.2015 In: Publications written by: Prof. Dr. Igor M. Sauer

European Surgical Research accepted our latest paper entitled "Implantation of a tissue engineered Neo Bile Duct in domestic pigs" for publication. Authors are B. Struecker, K. Hillebrandt, N. Raschzok, K. Jöhrens, A. Butter, P. Tang, A. Andreou, H. Napierala, D. Polenz, A. Reutzel-Selke, T. Denecke, J. Pratschke, and I.M Sauer.

Extrahepatic bile duct injuries remain severe complications during cholecystectomy and often require reconstruction by bilioenteric anastomosis (i.e. hepatico-jejunostomy), which comes along with further long-term complications (e.g. recurring ascending cholangitis, secondary biliary cirrhosis). Furthermore, in case of inherent extrahepatic biliary atresia or during liver transplant artificial or engineered bile ducts could enable novel surgical strategies without the need for hepatico-jejunostomy. We present data on the implantation of in vitro generated Neo Bile Ducts in five domestic pigs. Neo Bile Ducts were engineered through decellularization of allogeneic blood vessels and recellularization with autologous cholangiocytes.On postoperative days 0, 1, 7 and 14 blood samples were taken and analyzed (AST, ALT, Bilirubin, Alkaline Phosphatase, Creatinine and Leukocytes). An magnetic resonance cholangiography was performed on postoperative day 14 with one pig. 14 days after implantation pigs were sacrificed and bile ducts were explanted. All pigs survived the complete study period without severe complications. None of the pigs showed signs of biliary leakage or peritonitis. Neo Bile Ducts were infiltrated by neutrophils and neo-angiogenesis was observed around and into the implanted tissue. Whether the presented technique enables the long-term replacement of native bile ducts has to be further evaluated.

Human hepatocyte isolation – new paper

21.09.2015 In: Publications written by: Prof. Dr. Igor M. Sauer

Tissue Engineering, Part C: Methods accepted our paper „Human hepatocyte isolation: Does portal vein embolization affect the outcome?“ Authors are Martin Kluge, Anja Reutzel-Selke, Hendrik Napierala, Karl H. Hillebrandt, Rebeka D. Major, Benjamin Struecker, Annekatrin Leder, Jeffrey Siefert, Peter Tang, Steffen Lippert, Daniel Seehofer, Johann Pratschke, Igor M. Sauer und Nathanael Raschzok.

Primary human hepatocytes are widely used for basic research, pharmaceutical testing, and therapeutic concepts in regenerative medicine. Human hepatocytes can be isolated from resected liver tissue. Preoperative portal vein embolization (PVE) is increasingly used to decrease the risk of delayed postoperative liver regeneration by induction of selective hypertrophy of the future remnant liver tissue. The aim of this study was to investigate the effect of PVE on the outcome of hepatocyte isolation. Primary human hepatocytes were isolated from liver tissue obtained from partial hepatectomies (n=190) using the two-step collagenase perfusion technique followed by Percoll purification. Of these hepatectomies, 27 isolations (14.2%) were performed using liver tissue obtained from patients undergoing PVE prior to surgery. All isolations were characterized using parameters that had been described in the literature as relevant for the outcome of hepatocyte isolation. The PVE and non-PVE groups were similar in regard to donor parameters (sex, age, indication for surgery), isolation parameters (liver weight, cold ischemic time), and the quality of the liver tissue. The mean initial viable cell yield did not differ between the PVE and non-PVE groups (10.16±2.03x106 cells/g vs. 9.70±0.73 x106 cells/g, p=0.499). The initial viability was slightly better in the PVE-group (77.8 ±2.03% vs. 74.4 ±1.06%). The mean viable cell yield (p=0.819) and the mean viability (p=0.141) after Percoll purification did not differ between the groups. PVE had no effect on enzyme leakage and metabolic activity of cultured hepatocytes. Although PVE leads to drastic metabolic alterations and changes in hepatic blood flow, embolized liver tissue is a suitable source for the isolation of primary human hepatocytes and is equivalent to untreated liver tissue in regard to cell yield and viability.

Dr. Jan Schröder

18.09.2015 In: Thesis written by: Prof. Dr. Igor M. Sauer

Today, Jan Schröder successfully defended his thesis (summa cum laude) entitled "Vergleichende in vivo und in vitro Analysen im Rahmen der Etablierung der kombinierten Leber- und Leberzelltransplantation im Rattenmodell" !

Congratulations !

Karl Hillebrandt – YPT Rising Star

17.09.2016 In: Award written by: Prof. Dr. Igor M. Sauer

Karl Hillebrandt won this year's YPT Rising Stars Video Session Award. He presented the studies on „Optimized decellularization of rat livers by arterial and portal venous perfusion under oscillating pressure conditions“ during the 17th congress of the European Society for Organ Transplantation (ESOT) 2015 in Brüssel. Young Professionals in Transplantation (YPT) is a forum for junior professionals throughout Europe working in the field of transplantation.

The Morning After

31.08.2015 In: Publications written by: Prof. Dr. Igor M. Sauer

Referring to our paper „CD44 and CXCL9 serum protein levels predict the risk of clinically significant allograft rejection after liver transplantation“ Geoffrey W. McCaughan, Patrick Bertolino and David G. Bowen wrote an interesting editorial entitled „Could The Morning After liver transplant be immunologically interesting?“

They conclude, „that our study urges us to study the immune system response in liver allograft recipients during the very early phases after liver transplantation and to explore how events in immune organs and the allograft are reflected within the serum. Whether the patterns observed truly represent early detection of ACR versus tolerance, or a combination of both, requires further study and experimentation, including the identification of the cellular sources of these and other potential markers of immune outcome. It seems that despite significant levels of immunosuppressive drugs, immune activation and engagement occurs very early after human liver transplant, within the first 24 hours, in a manner that may have similarities with experimental animal models. Thus, the morning after effect could be an exciting window to longer-term immune outcomes, rather than just being preoccupied with observing important routine outcomes and detecting early complications.“

Tags: Liver,Biomarkers,LTx

Publication in Jove

10.08.2015 In: Publications written by: Prof. Dr. Igor M. Sauer

„Procedure for Decellularization of Rat Livers in an Oscillating-pressure Perfusion Device“ is available in J Vis Exp. 2015 Aug 10;(102). doi: 10.3791/53029 – accessible via the JOVE servers.

Authors are K. Hillebrandt, D. Polenz, A. Butter, P. Tang, A. Reutzel-Selke, A. Andreou, H. Napierala, N. Raschzok, J. Pratschke, I.M. Sauer, and B. Struecker . The presented techniques for liver harvesting, cannulation and perfusion using our proprietary device enable sophisticated perfusion set-ups to improve decellularization and recellularization experiments in rat livers.

Tags: Decellularisation,Liver

microRNAs in liver tissue engineering

16.06.2015 In: Publications written by: Prof. Dr. Igor M. Sauer

Our paper "microRNAs in liver tissue engineering - New promises for failing organs"was accepted for publication in Advanced Drug Delivery Reviews (IF: 15.038). Authors are Nathanael Raschzok, Hannes Sallmon, Johann Pratschke and Igor M. Sauer.

miRNA-based technologies provide attractive tools for several liver tissue engineering approaches. Herein, we review the current state of miRNA applications in liver tissue engineering. Several miRNAs have been implicated in hepatic disease and proper hepatocyte function. However, the clinical translation of these findings into tissue engineering has just begun. miRNAs have been successfully used to induce proliferation of mature hepatocytes and improve the differentiation of hepatic precursor cells. Nonetheless, miRNA-based approaches beyond cell generation have not yet entered preclinical or clinical investigations. Moreover, miRNA-based concepts for the biliary tree have yet to be developed. Further research on miRNA based modifications, however, holds the promise of enabling significant improvements to liver tissue engineering approaches due to their ability to regulate and fine-tune all biological processes relevant to hepatic tissue engineering, such as proliferation, differentiation, growth, and cell function.

CD44 and CXCL9 predicting rejection after LTx

21.04.2015 In: Publications written by: Prof. Dr. Igor M. Sauer

Based on a fruitful collaboration with the department of Visceral, Transplantation, Thoracic, and Vascular Surgery at the University of Leipzig our paper on „CD44 and CXCL9 serum protein levels predict the risk of clinically significant allograft rejection after liver transplantation“ has been accepted for publication in Liver Transplantation.

Authors are Nathanael Raschzok, Anja Reutzel-Selke, Rosa Bianca Schmuck, Mehmet Haluk Morgul, Ulrich Gauger, Kukuh Aji Prabowo, Laura-Marie Tannus, Annekatrin Leder, Benjamin Struecker, Sabine Boas-Knoop, Michael Bartels, Sven Jonas, Christian Lojewski, Gero Puhl, Daniel Seehofer, Marcus Bahra, Andreas Pascher, Johann Pratschke, and Igor Maximilian Sauer.

The diagnosis of acute cellular rejection (ACR) after liver transplantation is based on histological analysis of biopsies because non-invasive biomarkers for allograft rejection are not yet established for clinical routines. CD31, CD44, and CXCL9 have previously been described as biomarkers for cross-organ allograft rejection. Here, we assessed the predictive and diagnostic value of these proteins as serum biomarkers for clinically significant ACR in the first six months after liver transplantation in a prospective study. The protein levels were measured in 94 patients immediately prior to transplantation, at postoperative days (POD) 1, 3, 7, and 14, and when biopsies were performed during episodes of biochemical graft dysfunction. Our results suggest that CD44 and CXCL9 may serve as predictive biomarkers to identify liver allograft recipients at risk for clinically significant ACR.

Cover – march issue of Tissue Engineering

02.03.2015 In: Publications written by: Prof. Dr. Igor M. Sauer

One of the figures of our paper „Porcine liver decellularization under oscillating pressure conditions – A technical refinement to improve the homogeneity of the decellularization process“ made it to the cover of the march issue of Tissue Engineering, Part C : Methods.

Congratulations to Dietrich Polenz, who made the corrosion cast of a decellularized pig liver matrix: red, hepatic artery; blue, portal vein; yellow, bile duct and gallbladder.

Particles for microRNA-targeted manipulation

28.01.2015 In: Publications written by: Prof. Dr. Igor M. Sauer

Biomaterials accepted our paper on „Micron-sized iron oxide-containing particles for microRNA-targeted manipulation and MRI-based tracking of transplanted cells“. Authors are Annekatrin Leder, Nathanael Raschzok, Christian Schmidt, Duygu Arabacioglu, Antje Butter, Susanne Kolano, Luisa S. de Sousa Lisboa, Wiebke Werner, Dietrich Polenz, Anja Reutzel-Selke, Johann Pratschke, and Igor M. Sauer.

Particle-based delivery systems for therapeutic manipulation and tracking of transplanted cells by magnetic resonance imaging (MRI) are commonly based on nanometer-sized superparamagnetic iron oxide particles (SPIOs). Here, we present a proof of concept for multifunctional, silica based micron-sized iron oxide-containing particles (sMPIO) that combine fluorescence imaging, MRI tracking, and on-the-spot targeting of specific microRNAs on a particle surface for therapeutic manipulation by RNA interference. Antisense locked nucle-LNA) were covalently bound to the surface of silica-based, DAPI-integrated, micron-sized iron oxide particles (sMPIO--LNA). In vitro studies using primary human hepatocytes showed rapid particle uptake (4 hours) that was accompanied by significant depletion of the targeted microRNA Let7g (80%), up- regulation of the target proteins Cyclin D1 and c-Myc, and specific proteome changes. sMPIO--LNA- labeled cells were successfully detected by fluorescence imaging and could be visualized by MRI after intrasplenic transplantation in rats. This new theranostic particle provides a promising tool for cell transplantation where cellular imaging and microRNA-based manipulation is needed.

Biomaterials is the leading journal in its field. Impact factors released by ISI in July 2014 showed Biomaterials with an impact factor of 8.312!

Tags: Particles

Decellularization of pancreata – EPITA Award

28.01.2015 In: Meetings |Award written by: Prof. Dr. Igor M. Sauer

Ben Strücker presented our latest results on DECELLULARIZATION OF WHOLE RAT PANCREATA – EVALUATION OF THREE DIFFERENT PERFUSION ROUTES at the 5th EPITA Winter Symposium in Innsbruck from the 25th to the 27th of January 2015. He received the AIDPIT&EPITA Award for the best oral presentation. Congratulations!

Ben Strücker presented three effective protocols for rat pancreas perfusion decellularization, evaluating different perfusion routes. In contrast to liver decellularization the perfusion route seems to have no major impact on decellularization results. The dPECMs could serve for cellular repopulation with islets from a different (xenogene) origin to generate functional, transplantable endocrine pancreata in vitro.

Tags: Decellulariztaion,Pancreas

Rebeka Major: BIH Promotionsstipendium

10.12.2014 In: Grant |General written by: Prof. Dr. Igor M. Sauer

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.

Tags: INDY,Liver,Regeneration

ESAO 2015 in Leuven, Belgium

01.11.2014 In: Meetings written by: Prof. Dr. Igor M. Sauer

Tags: ESAO

Presentations at DTG 2014

30.10.2014 In: Meetings written by: Prof. Dr. Igor M. Sauer

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“.

Tags: DTG,Decellularization,miRNA

Ben Strücker: Charité Clinical Scientist

10.10.2014 In: Meetings written by: Prof. Dr. Igor M. Sauer

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.

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