News

DFG-funded ExTra Trial
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Prof. Dr. Nathanael Raschzok received a grant of € 1.85 million for the first three years from the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) for the Pilot, open, prospective, randomized, multicenter trial on expanding the donor pool by quality assessment of liver grafts declined for transplantation by normothermic ex vivo liver perfusion – ExTra. Co-applicants and/or significantly involved in the preparation of the study were Prof. Dr. Johann Pratschke, Prof. Dr. Igor M. Sauer, Prof. Dr. Dominik Modest, and Priv.-Doz. Dr. Simon Moosburner.

Liver transplantation in Germany is severely limited by a critical shortage of acceptable grafts and a high mortality rate on the waiting list. Furthermore, a significant number of organs are declined due to quality concerns. As demonstrated in pilot studies in the UK, Netherlands, Australia, and the United States, declined liver grafts can and should be used for transplantation after quality assessment by normothermic ex vivo liver machine perfusion (NMP).

The ExTra trial is a randomized controlled trial with a specific focus on patients with a model for end-stage liver disease (MELD) score ≤25 that are not eligible for (non)standard MELD exceptions. This cohort of patients faces an unacceptably long wait time for transplantation, which increases their mortality risk while on the waitlist. The ExTra trial aims to demonstrate that the time-to-transplant for these patients is shortened through the use of grafts that were initially declined for transplantation but fulfill specified quality criteria on normothermic ex vivo machine perfusion assessment. A total of 186 patients will be randomized in a 1:1 fashion to the experimental arm, which consists of a 12-month option to receive a liver graft that was declined by all German transplant centers but meets specified quality criteria, in addition to listing for liver transplantation through the standard allocation process. The control arm will consist of patients who are waitlisted for liver transplantation through the standard allocation process. Liver grafts that have been declined for transplantation must meet specific quality criteria. These include a maximum of 60% macrovesicular steatosis, no fibrosis greater than stage F3, and no cirrhosis. In line with previously published viability criteria for initially declined liver grafts, the decision to use or decline the graft will be made at least four hours after the start of perfusion.

The ExTra trial aims to show that by expanding the donor pool to include the ExTra option of non-transplantable organs, which appear to be usable after machine perfusion, patients without a high MELD score can be transplanted significantly faster. The ExTra trial is thus the first study worldwide in which this concept will be investigated in a randomized clinical trial. The study should make an important contribution to expanding the donor pool for liver transplants and thus ultimately help all patients on the waiting list for liver transplantation.

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Cytokine-armed vaccinia virus promotes cytotoxicity towards pancreatic carcinoma cells
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The manuscript "Cytokine-armed vaccinia virus promotes cytotoxicity towards pancreatic carcinoma cells via activation of human intermediary CD56dimCD16dim natural killer cells" by Ruonan Wang, Mengwen Hu, Isis Lozzi, Cao Z.J. Jin, Dou Ma, Katrin Splith, Jörg Mengwasser, Vincent Wolf, Linda Feldbrügge, Peter Tang, Lea Timmermann, Karl H. Hillebrandt, Marieluise Kirchner, Philipp Mertins, Georg Hilfenhaus, Christopher Neumann, Thomas Kammertoens, Johann Pratschke, Thomas Malinka, Igor Sauer, Elfriede Nössner, Zhongsheng Guo and Matthäus Felsenstein has been accepted for publication in the International Journal of Cancer.
 
Pancreatic ductal adenocarcinoma (PDAC) remains a particularly aggressive disease with few effective treatments. The PDAC tumor immune microenvironment (TIME) is known to be immune suppressive. Oncolytic viruses can increase tumor immunogenicity via immunogenic cell death(ICD). We focused on tumor-selective (vvDD) and cytokine-armed Western-Reserve vaccinia viruses (vvDD-IL2, vvDD-IL15) and infected carcinoma cell lines as well as patient-derived primary PDAC cells. In co-culture experiments, we investigated the cytotoxic response and the activation of human natural killer cells (NK). Infection and virus replication were assessed by measuring virus encoded YFP. We then analyzed intracellular signaling processes and oncolysis via in-depth proteomic analysis, immunoblotting and TUNEL assay. Following the co-culture of mock or virus infected carcinoma cell lines with allogenic PBMCs or NK cell lines, CD56+ NK cells were analyzed with respect to their activation, cytotoxicity and effector function. Both, dose- and time-dependent release of danger signals following infection was assayed. Viruses effectively entered PDAC cells and emitted YFP signals. Infection resulted in concomitant oncolysis. The proteome showed reprogramming of normally active core signaling pathways in PDAC occurred(e.g. MAPK-ERK signaling). Danger-associated molecular patterns were released upon infection and stimulated co-cultured NK cells for enhanced effector cytotoxicity. NK cell subtyping revealed enhanced numbers and activation of a rare CD56dimCD16dim population. Tumor cell killing was primarily triggered via Fas ligands rather than granule release, resulting in marked apoptosis. Cytokine-armed vaccinia viruses induced NK cell activation and enhanced cytotoxicity towards human PDAC cells in vitro. The cytokine-armed virus targets the carcinoma cells with great potential to modulate the TIME in PDAC.
Deutschlandfunk: AI in the operating theater
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How artificial intelligence supports surgeons: Planning surgical procedures, monitoring patients or predicting complications: there are already many useful applications for AI in the operating theater in research. In hospitals, the technology is still an exception. This is likely to change soon.
A Deutschlandfunk radio show/podcast by Carina Schroeder and Friederike Walch-Nasseri reports on the work in our Digital Surgery Lab (in German).
 
Artificial intelligence is revolutionizing our everyday lives. It translates texts, filters news, analyzes X-ray images and decides who gets a job. In the “KI verstehen (Understanding AI)” podcast, Deutschlandfunk provides answers to questions about dealing with AI every week.

Induced pluripotent stem cell (iPSC) line (EXSURGi001-A) from a patient homozygous for the p.Ala165Thr mutation in the MTARC1 gene
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The paper "Induced pluripotent stem cell (iPSC) line (EXSURGi001-A) from a patient homozygous for the p.Ala165Thr mutation in the MTARC1 gene" in Stem Cell Research is available open access. Authors are Peter Tang, Eriselda Keshi, Silvana Wilken, Louise Wutsdorff, Julienne Mougnekabol, Johann Pratschke, Igor M. Sauer and Nils Haep.

Metabolic dysfunction-associated fatty liver disease (MAFLD), the leading cause of end-stage liver disease in developed countries, is expected to increase over the next decade. Characterized by hepatic steatosis, MAFLD is commonly studied in animal models.
Here, we generated a human induced pluripotent stem cell (iPSC) line from a patient homozygous of the protective MTARC1 gene variant rs2642438:A.
This line displays a normal karyotype and typical pluripotent stem cell morphology and can differentiate into all three germ layers in vitro.
Extracellular NAD+ Response to Post-Hepatectomy Liver Failure: Bridging Preclinical and Clinical Findings
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Our manuscript entitled "Extracellular NAD+ Response to Post-Hepatectomy Liver Failure: Bridging Preclinical and Clinical Findings" has been accepted for publication in Communications Biology. Authors are Can Kamali, Philipp Brunnbauer, Kaan Kamali, Al-Hussein Saqr, Alexander Arnold, Gulcin Harman Kamali, Julia Babigian, Eriselda Keshi, Raphael Mohr, Matthäus Felsenstein, Simon Moosburner, Karl Hillebrandt, Jasmin Bartels, Igor Sauer, Frank Tacke, Moritz Schmelzle, Johann Pratschke, and Felix Krenzien.

Liver fibrosis progressing to cirrhosis is a major risk factor for liver cancer, impacting surgical treatment and survival. Our study investigates extracellular Nicotinamide adenine dinucleotide (eNAD+) in liver fibrosis, analyzing patients undergoing surgery and exploring NAD+'s therapeutic potential in a mouse model of extended liver resection and in vitro using 3D hepatocyte spheroids.

eNAD+ correlated with aspartate transaminase (AST) and bilirubin after liver resection (AST: r = 0.2828, p = 0.0087; Bilirubin: r = 0.2584, p = 0.0176). Post-hepatectomy liver failure (PHLF) was associated with higher eNAD+ peaks (n = 10; p = 0.0063). Postoperative eNAD+ levels decreased significantly (p < 0.05), but in advanced liver fibrosis or cirrhosis, this decline diminished or increased. NAD+ biosynthesis enzymes, NAMPT and NMNAT3, were significantly upregulated in higher fibrosis stages (p < 0.0001). NAD+ administration in 3D hepatocyte spheroids rescued hepatocytes from TNFα-induced cell death and improved viability (p < 0.0001). In mice, NAD+ treatment significantly improved survival (p = 0.0155) and liver regeneration (p = 0.0186) after extended liver resection.

eNAD+ is upregulated in PHLF, and NAD+ biosynthesis enzymes show higher expression in liver fibrosis. eNAD+ administration improved survival and hepatocyte viability, offering a potential target for future therapies.

Viscoelastic properties of colorectal liver metastases reflect the tumour cell viability
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Our paper on "Viscoelastic properties of colorectal liver metastases reflect the tumour cell viability" has been accepted for publication in Journal of Translational Medicine.

Colorectal cancer is one of the third most common cancers in the world and up to 50% of the patients develop liver metastases (CRLM) within five years. To improve and personalize therapeutic strategies, new diagnostic tools are urgently needed. An improvement could be achieved by considering biomechanical tumour properties with the implementation of magnetic resonance elastography (MRE). Our main hypothesis is that ex vivo MRE combined with histological evaluation of CRLM could provide the knowledge for using tissue mechanical properties as a diagnostic marker for cell viability in tumours.

We examined 34 CRLM samples from patients who had undergone liver resection at the Charité – Universitätsmedizin Berlin, Department of Surgery. The samples were investigated with an ex vivo MRE.  We employed a frequency range from 500 Hz to 5300 Hz, with increments of 400 Hz. For histological analysis, the samples were stained with H&E for categorization by a board-certified pathologist based on their grade of regression. The radiological response was evaluated using the RECIST-criteria.

Five samples showed major response to chemotherapy, 6 samples partial response, and 23 samples showed no response. Analysis of shear wave speed c significant correlation for frequencies including 2100 Hz and above depending on the grade of regression, indicating that low cell viability in CRLM is associated with higher tumour stiffness. Analysis of frequency-independent values of the SP-model showed a more elastic-solid behaviour at low cell viability. Our results suggest that MRE can be used to characterize the biomechanical properties associated with cell viability in CRLM, showing a higher stiffness and elastic-solid behaviour with high regression. In the future, MRE could help to improve the diagnostic tools to create an individual, tailored therapy plan for patients with CRLM.

Authors are Lisa-Marie Skrip, Simon Moosburner, Peter Tang, Jing Guo, Steffen Görner, Heiko Tzschätzsch, Clarissa Hosse, Uli Fehrenbach, Alexander Arnold, Dominik Modest, Felix Krenzien, Wenzel Schöning, Thomas Malinka, Johann Pratschke, Björn Papke, Josef A. Käs, Ingolf Sack, Igor M. Sauer, and Karl H. Hillebrandt,
Distinctive protein expression in elderly livers in a Sprague-Dawley rat model of normothermic ex vivo liver machine perfusion
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Our manuscript “Distinctive protein expression in elderly livers in a Sprague-Dawley rat model of normothermic ex vivo liver machine perfusion” has been published in the latest issue of the European Journal of Medical Research,
Authors are Maximilian Zimmer, Karl H. Hillebrandt, Nora M. Roschke, Steffen Lippert, Oliver Klein, Grit Nebrich, Joseph M.G.V. Gassner, Felix Strobl, Johann Pratschke, Felix Krenzien, Igor M. Sauer, Nathanael Raschzok, and Simon Moosburner.

Liver grafts are frequently declined due to high donor age or age mismatch with the recipient. To improve the outcome of marginal grafts, we aimed to characterize the performance of elderly vs. young liver grafts in a standardized rat model of normothermic ex vivo liver machine perfusion (NMP).

Livers from Sprague-Dawley rats aged 3 or 12 months were procured and perfused for 6 h using a rat NMP system or collected as a reference group (n = 6/group). Tissue, bile, and perfusate samples were used for biochemical, and proteomic analyses.

All livers cleared lactate during perfusion and continued to produce bile after 6 h of perfusion (614 mg/h). Peak urea levels in 12-month-old animals were higher than in younger animals. Arterial and portal venous pressure, bile production and pH did not differ between groups. Proteomic analysis identified a total of 1477 proteins with oxidoreductase and catalytic activity dominating the gene ontology analysis. Proteins such as aldehyde dehydrogenase 1A1 and 2-Hydroxyacid oxidase 2 were significantly more present in livers of older age.

Young and elderly liver grafts exhibited similar viability during NMP, though proteomic analyses indicated that older grafts are less resilient to oxidative stress. Our study is limited by the elderly animal age, which corresponds to mature but not elderly human age typically seen in marginal human livers. Nevertheless, reducing oxidative stress could be a promising therapeutic target in the future.
Thrombogenicity assessment of perfusable tissue engineered constructs: a systematic review
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Our systematic review on "Thrombogenicity assessment of perfusable tissue engineered constructs" has been accepted for publication in Tissue Engineering, Part B, and is available online ahead of print.

Vascular surgery faces a critical demand for novel vascular grafts that are biocompatible and thromboresistant. This urgency particularly applies to bypass operations involving small caliber vessels. In the realm of tissue engineering, the development of fully vascularized organs holds great promise as a solution to organ shortage for transplantation. To achieve this, it is imperative to (re-)construct a biocompatible and non-thrombogenic vascular network within these organs. In this systematic review, we identify, classify and discuss basic principles and methods used to perform in vitro/ex vivo dynamic thrombogenicity testing of perfusable tissue engineered organs and tissues. We conducted a pre-registered systematic review of studies published in the last 23 years according to PRISMA-P Guidelines, comprising a systematic data extraction, in-depth analysis and risk of bias assessment of 116 included studies. We identified shaking (n=28), flow loop (n=17), ex vivo (arterio-venous shunt, n=33) and dynamic in vitro models (n=38) as main approaches for thrombogenicity assessment. This comprehensive review unveils a prevalent lack of standardization and serves as a valuable guide in the design of standardized experimental setups.

Authors are Luna M. Haderer, Yijun Zhou, Peter Tang, Assal Daneshgar, Brigitta Globke, Felix Krenzien, Anja Reutzel-Selke, Marie Weinhart, Johann Pratschke, Igor M. Sauer, Karl H. Hillebrandt, and Eriselda Keshi.
Fritz Linder Prize 2024
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At the 141st German Surgical Congress (DCK 2024), Dr. Friederike Martin received the Fritz Linder Prize 2024 of the German Society of Surgery! The Forum Prize is awarded to the first author of the best presentation within the Surgical Forum. Friederike was honored for her work "Aging is transferable: Old Organs Accelerate Aging and Induce Senescence in Young Recipients“.
In Leipzig, she presented the results of her DFG-funded work with the phantastic team in the laboratory of Stefan G. Tullius, MD, PhD, Division of Transplant Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard University Medical School, in Boston. Her exciting results are another example of the fruitful axis between Stefan's laboratory and the Experimental Surgery in Berlin, which is funded by the Einstein Foundation Berlin!

Congratulations!
Quality assessment by bile composition in normothermic machine perfusion of rat livers
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Our manuscript “Quality assessment by bile composition in normothermic machine perfusion of rat livers” has been accepted for publication in Tissue Engineering Part A.
Authors are Vanessa Muth, Felix Stobl, Julian Michelotto, Jennifer A. Kirwan, Jeremy Marchand, Nathalie N. Roschke, Simon Moosburner, Johann Pratschke, Igor M. Sauer, Nathanael Raschzok, and Joseph MGV Gassner.

Due to the persistent challenge of organ scarcity in liver transplantation, there is an escalating dependence on organs obtained from extended criteria donors (ECD). Normothermic machine perfusion (NMP) can be used for improved preservation and allows quality assessment of ECD grafts. The primary objective of this study was to assess bile composition within the framework of quality analysis and explore the impact of warm ischemia on its composition in a rodent NMP model.

30 livers from male Sprague Dawley rats were divided into five distinct groups. Each group was subjected to 6 hours of NMP using either DMEM or Steen solution as perfusate, with or without a preceding 30-minute warm ischemia period. We further examined the effect of pressure-controlled perfusion on livers experiencing 30 min WIT using Steen as perfusate. We conducted regular measurements of AST, ALT, LDH, and urea levels in the perfusate at three- hour intervals. We collected bile samples at hourly intervals and assessed biliary pH, LDH, and GGT. Bile acids were measured using mass spectrometry every two hours.

Liver injury parameters were significantly higher in our DCD model. Bile production was significantly reduced in livers exposed to warm ischemia, and the bile showed a significantly more alkaline pH. This correlated with the concentration of total bile acids, which was significantly higher in livers with 30 min WIT. Taurocholic acid and its metabolites were most prominent. Secondary bile acids were significantly reduced in the course of perfusion due to the missing enterohepatic circulation. Prolonged warm ischemia-induced liver injury affects parameters we measured in bile within our small animal NMP model. We hypothesize that this phenomenon may be attributed to the cAMP-driven nature of bile secretion, potentially explaining why DCD livers produce less, yet more concentrated, bile.
A new bicornuate model of rat uterus transplantation
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Our work on a “A new bicornuate model of rat uterus transplantation” has been accepted for publication in Acta Obstetricia et Gynecologica Scandinavica.

Uterus transplantation has revolutionized reproductive medicine for women with absolute uterine factor infertility, resulting in more than 40 reported successful live births worldwide to date. Small animal models are pivotal to refine this surgical and immunological challenging procedure aiming to enhance safety for both the mother and the child.
We established a syngeneic bicornuate uterus transplantation model in young female Lewis rats. All surgical procedures were conducted by an experienced and skilled microsurgeon who organized the learning process into multiple structured steps. Animals underwent meticulous preoperative preparation and postoperative care. Transplant success was monitored by sequential biopsies, monitoring graft viability and documenting histological changes long-term. Bicornuate uterus transplantation were successfully established achieving an over 70% graft survival rate with the passage of time. The bicornuate model demonstrated safety and feasibility, yielding outcomes comparable to the unicornuate model in terms of ischemia times and complications. Longitudinal biopsies were well-tolerated, enabling comprehensive monitoring throughout the study. Our novel bicornuate rat uterus transplantation model provides a distinctive opportunity for sequential biopsies at various intervals after transplantation and therefore comprehensive monitoring of graft health, viability, and identification of potential signs of rejection. Furthermore, this model allows for different interventions in each horn for comparative studies without interobserver differences contrary to the established unicornuate model. By closely replicating the clinical setting, this model stands as a valuable tool for ongoing research in the field of uterus transplantation, promoting further innovation and deeper insights into the intricacies of the uterus transplant procedure.

Authors are Dietrich Polenz, Igor Maximilian Sauer, Friederike Martin, Anja Reutzel-Selke, Muhammad Imtiaz Ashraf , Anja Schirmeier , Steffen Lippert, Kirsten Führer, Johann Pratschke, Stefan Günther Tullius, and Simon Moosburner.
Depletion of donor dendritic cells ameliorates immunogenicity of both skin and hind limb transplants
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Our manuscript "Depletion of donor dendritic cells ameliorates immunogenicity of both skin and hind limb transplants" has been accepted for publication in Frontiers in Immunology, section Alloimmunity and Transplantation. Authors are Muhammad Imtiaz Ashraf, Joerg Mengwasser, Anja Reutzel-Selke, Dietrich Polenz, Kirsten Führer, Steffen Lippert, Peter Tang, Edward Michaelis, Rusan Catar, Johann Pratschke, Christian Witzel, Igor M. Sauer, Stefan G. Tullius, and Barbara Kern.

Acute cellular rejection remains a significant obstacle affecting successful outcomes of organ transplantation including vascularized composite tissue allografts (VCA). Donor antigen presenting cells (APC), particularly dendritic cells (DC), orchestrate early alloimmune responses by activating recipient effector T cells. Employing a targeted approach, we investigated the impact of donor-derived conventional DC (cDC) and APC on the immunogenicity of skin and skin-containing VCA grafts, using mouse models of skin and hind limb transplantation.
By post-transplantation day 6, skin grafts demonstrated severe rejections, characterized by predominance of recipient CD4 T cells. In contrast, hind limb grafts showed moderate rejection, primarily infiltrated by CD8 T cells. While donor depletion of cDC and APC reduced frequencies, maturation, and activation of DC in all analysed tissues of skin transplant recipients, reduction in DC activities was only observed in the spleen of hind limb recipients. Donor cDC and APC depletion did not impact all lymphocyte compartments but significantly affected CD8 T cells and activated CD4 T in lymph nodes of skin recipients. Moreover, both donor APC and cDC depletion attenuated the Th17 immune response, evident by significantly reduced Th17 (CD4+IL-17+) cells in the spleen of skin recipients and reduced levels of IL-17E and lymphotoxin-α in the serum samples of both skin and hind limb recipients. In conclusion, our findings underscore the highly immunogenic nature of skin component in VCA. The depletion of donor APC and cDC mitigates the immunogenicity of skin grafts while exerting minimal impact on VCA.
Funding for "Expansion of Clinical Applications for the Human Muscle Stem Cell Product PHSat"
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The Investitionsbank Berlin (IBB) is funding the collaborative project "Expansion of Clinical Applications for the Human Muscle Stem Cell Product PHSat", initiated by the start-up company MyoPax in cooperation with the Departments of Surgery and Neurosurgery at the Charité.
 
Muscle diseases affect more than 20 million patients in Europe with limited therapeutic options. MyoPax, a spin-off of Charité and MDC, has developed a patented method to isolate and expand patient-specific muscle stem cell populations, known as PHSats (Primary Human Satellite-cell derived muscle stem cells), while preserving their regenerative potential.
 
The ProFit project aims to preclinically evaluate additional clinical applications for PHSats. The validation of new indications will lay the foundation for future clinical studies and the expansion of the market potential of PHSats. In a subproject led by Experimental Surgery and PI Priv.-Doz. Dr. Karl Hillebrandt, the preclinical application of decellularized diaphragms combined with PHSats to regenerate the impaired diaphragms of mice with muscular dystrophy will be explored. Two routes of administration will be investigated: direct injection into damaged diaphragms and transplantation onto degenerated diaphragms. The ultimate goal is to preserve or improve respiratory function by augmenting the diaphragm. This approach holds promise for several conditions, such as ventilator-induced diaphragm dysfunction or diaphragm atrophy due to COPD, where impaired diaphragm function affects respiratory capacity.
Surgical planning in virtual reality: a systematic review
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We just published a review on surgical planning in VR in the Journal of Medical Imaging. In the systematic review we look into how virtual reality (VR) is transforming surgical planning. With VR physicians can assess patient-specific image data in 3D, enhancing surgical decision-making and spatial localization of pathologies. We found that benefits of VR become more evident. However, its application in surgical planning remains experimental, with a need for refined study designs, improved technical reporting, and enhanced VR software usability for effective clinical implementation. Authors of "Surgical planning in virtual reality: a systematic review" are Prof. Dr. Moritz Queisner and Karl Eisenträger.

Virtual reality (VR) technology has emerged as a promising tool for physicians, offering the ability to assess anatomical data in 3D with visuospatial interaction qualities. This systematic review aims to provide an up-to-date overview of the latest research on VR in the field of surgical planning.
A comprehensive literature search was conducted based on the preferred reporting items for systematic reviews and meta-analyses covering the period from April 1, 2021 to May 10, 2023. The review summarizes the current state of research in this field, identifying key findings, technologies, study designs, methods, and potential directions for future research. Results show that the application of VR for surgical planning is still in an experimental stage but is gradually advancing toward clinical use. The diverse study designs, methodologies, and varying reporting hinder a comprehensive analysis. Some findings lack statistical evidence and rely on subjective assumptions. To strengthen evaluation, future research should focus on refining study designs, improving technical reporting, defining visual and technical proficiency requirements, and enhancing VR software usability and design. Addressing these areas could pave the way for an effective implementation of VR in clinical settings.
Spacial computing in the OR
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We tested the Apple Vision Pro in the operating theatre and it cuts an excellent figure: great images even in challenging lighting situations, stable interaction with the device - even though the limited peripheral vision and awareness inherent to video-based devices is a considerable downside in surgery.

We are looking forward to our first software solutions for improved hand-eye coordination in visceral surgery for this device too!
Optimizing environmental enrichment for Sprague Dawley rats: Exemplary insights into the liver proteome
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Considering the expected increase in the elderly population and the growing emphasis on aging-related biomedical research, the demand for aged laboratory animals has surged, challenging established husbandry practices. Our objective was to establish a cost-effective method for environmental enrichment, utilizing the liver as a representative organ to assess metabolic changes in response to differing enrichment levels.
We conducted a six-month study involving 24 male Sprague Dawley rats who were randomly assigned to four environmental enrichment groups. Two groups were housed in standard cages, while the others were placed in modified rabbit cages. Half of the groups received weekly playtime in an enriched rat housing unit. We evaluated hormone levels, playtime behavior, and subjective handling experience. Additionally, liver tissue proteomic analysis was performed.
Initial corticosterone levels and those after 3 and 6 months showed no significant differences. Yet, testosterone levels were lower in the control group by the end of the study (p=0.007). In the liver tissue, we detected 1,871 distinct proteins, with 77% of them being consistent across all groups. In gene ontology analysis, no specific pathways were overexpressed. In semiquantitative analysis, we observed differences in proteins associated in lipid metabolism such as Apolipoprotein A-I and Acyl-CoA 6-desaturase, which were lower in the control group (p= 0.024 and p=0.009). Enriched environments reduced rat distress, large cages eased handling, and conflicts between rats lessened with bi-weekly interactions.

The manuscript "Optimizing environmental enrichment for Sprague Dawley rats: Exemplary insights into the liver proteome" has been accepted for publication in PLOS ONE.
Authors are Nathalie N. Roschke, Karl H. Hillebrandt, Dietrich Polenz, Oliver Klein, Joseph MGV Gassner, Johann Pratschke, Felix Krenzien, Igor M. Sauer, Nathanael Raschzok, and Simon Moosburner.
Proteomic analysis of decellularized mice liver and kidney extracellular matrices
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Based on the collaboration between the Department of General, Visceral, and Transplant Surgery, University Hospital Münster, and Experimental Surgery, Department of Surgery, Charité – Universitätsmedizin Berlin our work on the "Proteomic analysis of decellularized mice liver and kidney extracellular matrices" has been accepted for publication in Journal of Biological Engineering.

In this study, we employed a bottom-up proteomic approach to elucidate the intricate network of proteins in the decellularized extracellular matrices of murine liver and kidney tissues. This approach involved the use of a novel, perfusion-based decellularization protocol to generate acellular whole organ scaffolds. Proteomic analysis of decellularized mice liver and kidney ECM scaffolds revealed tissue-specific differences in matrisome composition, while we found a predominantly stable composition of the core matrisome, consisting of collagens, glycoproteins, and proteoglycans. Liver matrisome analysis revealed unique proteins such as collagen type VI alpha-6, fibrillin-2 or biglycan. In the kidney, specific ECM-regulators such as cathepsin z were detected. The identification of distinct proteomic signatures provides insights into how different matrisome compositions might influence the biological properties of distinct tissues. This experimental workflow will help to further elucidate the proteomic landscape of decellularized extracellular matrix scaffolds of mice in order to decipher complex cell-matrix interactions and their contribution to a tissue-specific microenvironment.

Authors are Anna-Maria Diedrich, Assal Daneshgar, Peter Tang, Oliver Klein, Annika Mohr, Olachi A. Onwuegbuchulam, Sabine von Rueden, Kerstin Menck, Annalen Bleckmann, Mazen A. Juratli, Felix Becker, Igor M. Sauer, Karl H. Hillebrandt, Andreas Pascher, and Benjamin Struecker.
M. Pflüger: Resect or not to resect: Unravelling the Biology of Neoplastic Pancreatic Cysts Using Genetic Studies
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Michael Pflüger - currently research fellow at the Wood Lab, Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, Johns Hopkins University School of Medicine - will present the translational work of the Wood Laboratory and the interdisciplinary management of pancreatic neoplasia at Johns Hopkins Hospital as part of the monthly interdisciplinary event series "The Pancreatic Cancer Precision Medicine Center of Excellence Program (PMCoE) Seminar Series".

"Resect or not to resect: Unravelling the Biology of Neoplastic Pancreatic Cysts Using Genetic Studies - A Translational Approach"
29.01.2024, 22:00/10 pm CET
Zoom link: https://jhjhm.zoom.us/j/94712957898?pwd=NXpHZ1NneFJtdTgvekx4ZVI1MHE3UT09
miRNA as potential biomarkers after liver transplantation: A systematic review
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The publication "miRNA as potential biomarkers after liver transplantation: A systematic review" is now available online in Transplantation Reviews. Authors are Pia F. Koch, Kristina Ludwig, Felix Krenzien, Karl H. Hillebrandt, Wenzel Schöning, Johann Pratschke, Nathanael Raschzok, Igor M. Sauer, and Simon Moosburner.

Early and accurate diagnosis of acute cellular rejection (ACR) and graft complications after liver transplantation is crucial for timely intervention and improved patient outcomes, but their diagnosis rely currently on invasive biopsy sampling, thus prompting the search for non-invasive Biomarkers. MicroRNA (miRNA) have emerged as promising biomarkers in various pathological conditions, and their potential utility in diagnosing acute cellular rejection after liver transplantation has gained significant interest.

This systematic review analyzes studies exploring miRNA as biomarkers for ACR and graft dysfunction in liver transplantation (PROSPERO ID CRD42023465278). The Cochrane Collaboration tool for assessing risk of bias was employed. Population data, identified miRNA and their dynamic regulation, as well as event prediction were compared. Data extraction and quality assessment were performed independently by two reviewers.

The results highlight the potential of miRNA as specific, non-invasive biomarkers for ACR and graft dysfunction following liver transplantation. However, further research is needed to validate these findings and establish standardized diagnostic panels to incorporate them into clinical practice and explore miRNA-based therapies in the future.
AI-based intra- and postoperative measurement from stereoimages
The publication "Redefining the Laparoscopic Spatial Sense: AI-based Intra- and Postoperative Measurement from Stereoimages“ has been accepted for the 38th AAAI Conference on Artificial Intelligence and is available via https://doi.org/10.48550/arXiv.2311.09744. The publication is the result of a fruitful collaboration between Karlsruhe Institute of Technology (KIT), Fraunhofer FIT, University of Bayreuth, and Charité – Universitätsmedizin Berlin. Authors are Leopold Müller, Patrick Hemmer, Moritz Queisner, Igor Sauer, Simeon Allmendinger, Johannes Jakubik, Michael Vössing, and Niklas Kühl.

A significant challenge in image-guided surgery is the accurate measurement task of relevant structures such as vessel segments, resection margins, or bowel lengths. While this task is an essential component of many surgeries, it involves substantial human effort and is prone to inaccuracies. In this paper, we develop a novel human-AI-based method for laparoscopic measurements utilizing stereo vision that has been guided by practicing surgeons. Based on a holistic qualitative requirements analysis, this work proposes a comprehensive measurement method, which comprises state-of-the-art machine learning architectures, such as RAFT-Stereo and YOLOv8. The developed method is assessed in various realistic experimental evaluation environments. Our results outline the potential of our method achieving high accuracies in distance measurements with errors below 1 mm. Furthermore, on-surface measurements demonstrate robustness when applied in challenging environments with textureless regions. Overall, by addressing the inherent challenges of image-guided surgery, we lay the foundation for a more robust and accurate solution for intra- and postoperative measurements, enabling more precise, safe, and efficient surgical procedures.

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Priv.-Doz. Dr. med. Karl Hillebrandt
Today Karl Hillebrandt gave an exzellent inaugural lecture entitled „Die Geister, die ich rief ... – Eine kurze Geschichte der De- und Rezellularisierung“ and is now a private lecturer (Privatdozent) at the Charité – Universitätsmedizin Berlin and habilitated in the field of "Experimental Surgery".

He is being honored for his achievements in the field of tissue engineering. His postdoctoral thesis is entitled "New approaches for the characterisation of decellularised tissues and the recellularisation of vessels".

Congratulations!

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Rise of tissue- and species-specific 3D bioprinting based on decellularized extracellular matrix-derived bioinks and bioresins
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The publication "Rise of tissue- and species-specific 3D bioprinting based on decellularized extracellular matrix-derived bioinks and bioresins" is now available online in Biomaterials and Biosystems. Authors are Laura Elomaa, Ahed Almalla, Eriselda Keshi, Karl H. Hillebrandt, Igor M. Sauer, and Marie Weinhart.

Thanks to its natural complexity and functionality, decellularized extracellular matrix (dECM) serves as an excellent foundation for creating highly cell-compatible bioinks and bioresins. This enables the bioprinted cells to thrive in an environment that closely mimics their native ECM composition and offers customizable biomechanical properties. To formulate dECM bioinks and bioresins, one must first pulverize and/or solubilize the dECM into non-crosslinked fragments, which can then be chemically modified as needed. In bioprinting, the solubilized dECM-derived material is typically deposited and/or crosslinked in a layer-by-layer fashion to build 3D hydrogel structures. Since the introduction of the first liver-derived dECM-based bioinks, a wide variety of decellularized tissue have been employed in bioprinting, including kidney, heart, cartilage, and adipose tissue among others. This review aims to summarize the critical steps involved in tissue-derived dECM bioprinting, starting from the decellularization of the ECM to the standardized formulation of bioinks and bioresins, ultimately leading to the reproducible bioprinting of tissue constructs.
New DFG research group FOR 5628 with our participation
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The Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) is establishing eight new research groups. One of these groups is FOR 5628: "Multiscale magnetic resonance elastography in cancer: The mechanical niche of tumor formation and metastatic spread – towards an improved diagnosis of cancer through mechanical imaging". The speaker and initiator is Prof. Ingolf Sack.

During the development of a tumour, the tissue changes its shape, e.g., alternating between hard and fluidic states. For this, cells exert forces and are simultaneously influenced by forces. This research group is investigating which mechanical-physical processes are behind this. How do tumours and metastases develop? What makes them resistant to therapy? The team is investigating these questions using magnetic resonance elastography (MRE) – a new clinical procedure that can be used to record the mechanical properties of body tissue. The goal is to be able to better diagnose tumours.
Dr. Karl Hillebrandt and Prof. Dr. Igor Sauer are part of the research group as PI in three projects:
  • A03 Cancer cell unjamming and jamming as prerequisites for the formation of primary and metastatic tumors
  • B03 Scaffold composition and fluid pressure in recellularized hepatic and pancreatic tumors
  • C01 Multiscale mechanical properties of tumors and tumor environment – from tissue specimens to patients

Was are happy to be part of this exzellent team!
Moderate LMWH anticoagulation improves success rate of hind limb allotransplantation in mice
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The publication "Moderate LMWH Anticoagulation Improves Success Rate of Hind Limb Allotransplantation in Mice" is now available online in Plastic & Reconstructive Surgery-Global Open. Authors are B. Kern, M.-I. Ashraf, A. Reutzel-Selke, J. Mengwasser, D. Polenz, E. Michaels, J. Pratschke, S.G. Tullius, Ch. Witzel, and I.M. Sauer.

The mouse hind limb model represents a powerful research tool in vascularized composite tissue allotransplantation, but its applicability is limited due to poor graft survival (62%–83%). Vascular thrombosis and massive hemorrhage are the major causes for these drop-outs. We hypothesize that because of better anticoagulation effect and lower risk of thrombocytopenia, application of low molecular weight heparin (LMWH) will minimize vascular complications and enhance graft and animal survival.

Fifty allogeneic hind limb transplantations were performed (C57BL/6 to DBA/2 mice) using five different anticoagulation protocols. Bleeding and thromboembolic events were recorded macroscopically by postoperative hemorrhage and livid discoloration of the graft, respectively. Graft perfusion and survival were monitored daily by capillary-refill-time of graft toes within 2–3 seconds. Vascular congestion and tissue necrosis were examined by histological evaluation of hematoxylin-eosin-stained tissue sections.

All transplantations were technically successful. Increase in thromboembolic events and a concomitant decrease in bleeding events were observed with the decreasing concentration of heparin in the perfusion solution. Although treatment of donor and recipient with low dose of LMWH could not reduce thromboembolic events, moderate dose effectively reduced these events. Compared with the poor outcome of graft perfusion with heparin alone, additional treatment of donor and recipient with low dose of LMWH improved graft and animal survival by 18%. Interestingly, animals treated with moderate dose of LMWH demonstrated 100% graft and animal survival.
Treatment of donor and recipient mice with a moderate dose of LMWH prevents vascular complications and improves the outcome of murine hind limb transplants.
ECRT Consumable Grant - Advanced Scientists
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Nils Haep successfully applied for funding from the ECRT Consumable Grant - Advanced Scientists. In his project, Nils is investigating the function of a cysteine-type endopeptidase and described mutations in the endopeptidase in induced pluripotent stem cell derived hepatocytes and their influence on Adiponutrin induced NAFLD.

Congratulations!
Priv.-Doz. Dr. med. Simon Moosburner
Today Simon Moosburner gave his inaugural lecture on "Liver Transplantation in Germany - Opportunities and Solutions for the Future". He is now – at the age of 28 (!) – a private lecturer (Privatdozent) at the Charité – Universitätsmedizin Berlin and habilitated in the field of "Experimental Surgery".

He is being honored for his achievements in the field of extracorporeal organ perfusion and organ transplantation. His postdoctoral thesis is entitled "Challenges and solutions in adults and children after liver transplantation".

Congratulations!

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Dr. Zeynep Akbal
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We are delighted to welcome Dr. Zeynep Akbal as a new member of the team!
Before she started as a post-doctoral researcher at the Digital Surgery Lab she studied communication sciences, media sciences, philosophy, and worked on developing her interdisciplinary method around virtual reality (VR) technology. She did her doctorate in philosophy at Universität Potsdam. Her dissertation is recently published as a monograph, titled "Lived-Body Experiences in Virtual Reality. A Phenomenology of the Virtual Body.”
Her research focuses on the intersection of philosophy of perception, cognitive sciences and VR. In her recent research project “Tactile Stimulation in VR” at Max Planck Institute for Human Cognitive and Brain Sciences, she focused on the behavioral consequences of haptic feedback in a VR task.

Wellcome to the team!
science x media Tandem Program: "From Slices to Spaces"
Prof. Dr. Moritz Queisner and Frédéric Eyl (Designer and Managing Director of TheGreenEyl) successfully applied to the Stiftung Charité for funding as a "science x media tandem".
The science x media tandems are the first programme in the new funding priority "Open Life Science". With this funding priority, the Charité Foundation is working to make the life sciences in Berlin more comprehensible and accessible to a broader public and to strengthen the trustworthiness of medical professionals.

Under the title "From Slices to Spaces", the tandem of Moritz Queisner and Frédéric Eyl is implementing a science parcours in which spatially complex research data from surgery and biomedicine will be made multisensually accessible to a broad audience through new visualization techniques. Building on research work on new imaging techniques by Moritz Queisner, they employ Extended Reality techniques. Due to their unique ability to link digital objects with the real environment of the viewers, the 4D images they generate are particularly suited for representing and conveying spatial information.

This is where the tandem's project comes in: 4D images are not only interesting for researchers to understand complex research data but can also provide laypeople with a less presupposing insight into research data and processes. Frédéric Eyl's media expertise will be used to make the specific visual knowledge from research comprehensible and experiential for non-experts. The science parcours is intended to integrate as a digital extension into the architecture of the new research building, "Der Simulierte Mensch", located on the premises of Charité. The parcours will include the facade, the inter-floor airspace, and the central glass surfaces within the building as its stations. By enabling users to explore 4D research data within the architecture and investigate it using their own smartphones in an AR application, concrete practices and deployment locations of new image-based technologies become experiential and comprehensible. This project not only enhances the perception of Charité and the scientific location of Berlin but also opens up places of knowledge creation to the public, making practices and techniques of life sciences more visible.


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Eriselda Keshi and Simon Moosburner CSP fellows
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Dr. Eriselda Keshi and Dr. Simon Moosburner successfully applied for the BIH Charité Clinician Scientist Program (CSP).
The program provides a unique opportunity for young medical doc- tors to combine their clinical training with protected time for research. This structured career path fosters translation of scientific discoveries into application and strengthens the innovative capacity of academic medicine.
Participants of the CSP devote 50 percent of their working hours to research over a period of three years.

Dr. Keshi will work on "NeoPancreasPrint, a 3D printed islet hosting tissue based on biocompatible ink derived from human decellularized pancreas".
Dr. Moosburner applied with this project "Alleviation of Senescence induced Ischemia-Reperfusion in Liver Grafts of Elderly Donors [SenEx".



Congratulations!
Prof. Dr. Nathanael Raschzok
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Nathanael Raschzok | Experimental Surgery | 2007

With us in the team since he was a student, he has so far climbed all academic levels with flying colours.
In recognition of his outstanding achievements in research, teaching and the promotion of young academics, Nathanael was awarded the title of Associate Professor at the Charité – Universitätsmedizin Berlin.

Congratulations, Prof. Raschzok!
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 !
Work with us | PhD position
We offer a funded PhD position for a computational biologist @ Experimental Surgery, Charité – Universitätsmedizin Berlin!

Are you interested to work on cutting-edge cancer research, and investigating complex-chromosomal as well as other genomic phenomena in human carcinoma cells ?

  • You will work on complex genome analyses (single-cell analyses, whole genome analyses) to detect, annotate and re-construct circular DNA using state of the art computational tools (e.g., Amplicon architect).
  • We provide motivation and high commitment in supervision in areas around experimental oncology and surgery.
  • The position allows the applicant to pursue an academic qualification, while collaborating and networking with international experts on extrachromosomal circular DNA and pancreatic carcinogenesis.

Apply now!
Send brief cover letter and CV via email to Dr. med. Matthäus Felsenstein (matthaeus.felsenstein@charite.de)
Dr. Eriselda Keshi
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Today Eriselda Keshi successfully defended her doctoral thesis entitled "Construction of a thromboresistant vascular graft for vascular surgery purposes by decellularisation and recellularisation" summa cum laude!

Congratulations !
BIH Medical Student Research Stipend for Cao Zhong Jing Jin
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Cao Zhong Jing Jin under the supervision of Dr. med. Matthäus Felsenstein successfully applied for the BIH Medical Student Research Stipend on their project “Deciphering the molecular determinants for the transformation of high-grade pancreatic duct dysplasia to invasive carcinoma by single-cell transcriptomics”. She is conducting a cutting-edge research project merging molecular data with histological information in collaboration with the BIH core facilities for single-cell genomics (Dr. Thomas Conrad) and intelligent imaging (Prof. Dr. Christian Conrad). Using modern single-cell- and spatial transcriptomics on pancreatic precursor and carcinoma samples, the project aims at defining molecular signatures that drive dysplastic cells.

Congratulations!
New DFG project "4D Imaging"
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The DFG Schwerpunktprogramm „Das Digitale Bild“ (SPP 2172) funds the new project “4D Imaging: From Image Theory to Imaging Practice” (2023-2026). Principal investigators are Prof. Dr. Kathrin Friedrich (Universität Bonn) and Prof. Dr. Moritz Queisner.

The term 4D imaging refers to a new form of digital visuality in which image, action and space are inextricably interwoven. 4D technologies capture, process and transmit information about physical space and make it computable in real time. Changes due to movements and actions become calculable in real time, making 4D images particularly important in aesthetic and operational contexts where they reconceptualize various forms of human-computer interaction. The 4D Imaging project responds to the growing need in medicine to understand, use, and design these complex imaging techniques. It transfers critical reflexive knowledge from research into clinical practices to enable surgeons to use and apply 4D Imaging techniques. Especially in surgical planning, 4D Imaging techniques may improve the understanding and accessibility of spatially complex anatomical structures. To this end, the project is developing approaches to how 4D imaging can complement and transform established topographic ("2D") imaging practices.

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Work with us | PhD position

We are hiring: 3-year #PhD position @Charité – Universitätsmedizin Berlin.
  • Join our interdisciplinary team for a PhD on new #imaging technologies at the intersection of digital health, surgery and biomedicine
  • Explore new ways to understand and/or visualize anatomical structures in #4D using extended reality #XR #digitaltransformation
  • Connect theory and practice in an interdisciplinary research group
  • Open call: open to all disciplines! Yes, that’s right – design, computer science, computer visualistics, digital health, psychology, media studies, workplace studies, game design…
  • What counts is a convincing idea for your doctoral project in the field of "4D imaging“

Sounds interesting? Apply now or reach out to Moritz Queisner (moritz.queisner@charite.de) if you have any questions.

More information:
German: https://karriere.charite.de/stellenangebote/detail/wissenschaftliche-mitarbeiterin-wissenschaftlicher-mitarbeiter-dwm-technologietransfer-chirurgie-dm27222a
English: https://karriere.charite.de/stellenangebote/detail/scientific-researcher-phd-position-dfm-dm27222b

EKFS grant for functional role and clinical relevance of ecDNA in pancreatic adenocarcinoma
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Dr. Matthäus Felsenstein successfully applied for funding from the Else Kröner Fresenius Stiftung (EKFS) for his project “The functional role and clinical relevance of extrachromosomal DNA (ecDNA) in pancreatic adenocarcinoma”. In close collaboration with the excellence group around Professor Anton Henssen, he is aiming at improved understanding of unique genomic patterns as a results of complex chromosomal rearrangements in pancreatic adenocarcinoma that could drive its aggressive behavior. He will use state-of-the art three-dimensional tissue culture to enrich for neoplastic cells from primary PDAC specimen and subsequently perform genome analyses to identify samples that harbor extrachromosomal DNA. The clinical impact of these chromosomal structures will be explored by clinical correlation analyses and therapy response in vitro.

Congratulations!
"Einstein Kickbox - Advanced Scientists" grant
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Nils Haep successfully applied for the "Einstein Kickbox - Advanced Scientists" grant of the Einstein Center for Regenerative Therapies (ECRT). The purpose of the grant is to provide start-up funding for interesting experimental projects in regenerative medicine.  In his project, Nils is investigating the function of a cysteine-type endopeptidase and described mutations in the endopeptidase in hepatocytes using live-cell imaging and metabolomics. Through this preliminary work, he hopes to generate a hypothesis on the function of the endopeptidase and the underlying mechanism of the mutations. In the next step, he plans to develop a disease model for fatty liver from induced pluripotent stem cells.
Design Lab #13: Material Legacies
The exhibition »Design Lab #13: Material Legacies« at Kunstgewerbemuseum Berlin, opening on November 3rd, 2022, explores contingencies and ruptures between traditional crafts and the most recent developments at the crossroads of material research, design, engineering, and architecture. It brings together artifacts from the museum’s collection with work-in-progress installations by designers and researchers from the Cluster of Excellence »Matters of Activity. Image Space Material« in order to initiate a dialogue about the historical, contemporary, and future conditions under which materiality unfolds.

By engaging with a series of different materials and techniques the exhibition encompasses both the problematization of unsustainable pasts and presents as well as the imagination of speculative material futures. Taking materiality as a starting point, each of the exhibits will investigate its sociocultural, economic, and political context in order to disentangle the multiple interrelations that arise from and with materials. As such »Design Lab #13: Material Legacies« aims to challenge the passive understandings of materiality and associate with the widening discourse on relational knowledge practices in arts, design, humanities, and social science.

The exhibition will be running from 4 November 2022 to 26 February 2023. For the exhibition announcement on the website of the
Staatliche Museen zu Berlin – Preußischer Kulturbesitz.

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Exhibition Opening

3 November 2022, 6 pm

The opening event will include an introduction to the exhibition by Dr. Claudia Banz, Curator of Design at the Kunstgewerbemuseum Berlin, and Prof. Dr. Claudia Mareis, co-director of the Cluster of Excellence »Matters of Activity. Image Space Material«. Moreover, exhibition curators Michaela Büsse and Emile De Visscher will provide background on the exhibition, its goals, and how the curatorial process was undertaken.
The exhibition opening is part of the Berlin Science Week 2022.
BMBF funds KIARA
With the programme "AI-based assistance systems for process-accompanying health applications", the Federal Ministry of Education and Research (BMBF) is funding innovative research and development work on interactive assistance systems that support processes in clinical health care using artificial intelligence methods.

Together with the partners Gebrüder Martin GmbH & Co. KG, Tuttlingen, HFC Human-Factors-Consult GmbH, Berlin and the Fraunhofer Institute for Telecommunications Heinrich-Hertz-Institut (HHI), Berlin, we successfully applied with the project "AI-based recording of work processes in the operating theatre for the automated compilation of the operating theatre report" (KIARA).


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Operating theatre reports document all relevant information during surgical interventions. They serve to ensure therapeutic safety and accountability and as proof of performance. The preparation of the OR report is time-consuming and ties up valuable working time – time that is then not available for the treatment of patients.

In the KIARA project, we are working on a system that automatically drafts operating theatre reports. The KIARA system is intended to relieve medical staff: it documents operating theatre activities and creates a draft of the report, which then only needs to be checked, completed and approved. The system works via cameras integrated into operating theatre lamps. Their image data is then analysed with the help of artificial intelligence to recognise and record objects, people and all operating theatre activities. The ambitious system is to be developed and tested in a user-centred manner for procedures in the abdominal cavity and in oral and maxillofacial surgery.

KIARA is intended to continuously learn through human feedback and to simplify clinical processes for the benefit of medical staff by automating the creation of operating theatre reports. The system can also be applied to other operating theatre areas in the future.

The project has a financial volume of € 2.16 million.
The kick-off meeting took place on 16.09.2022 at the Charité.
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Our manuscript "Depletion of donor dendritic cells ameliorates immunogenicity of both skin and hind limb transplants" has been accepted for publication in Frontiers in Immunology, section Alloimmunity and Transplantation. Authors are Muhammad Imtiaz Ashraf, Joerg Mengwasser, Anja Reutzel-Selke, Dietrich Polenz, Kirsten Führer, Steffen Lippert, Peter Tang, Edward Michaelis, Rusan Catar, Johann Pratschke, Christian Witzel, Igor M. Sauer, Stefan G. Tullius, and Barbara Kern.

Acute cellular rejection remains a significant obstacle affecting successful outcomes of organ transplantation including vascularized composite tissue allografts (VCA). Donor antigen presenting cells (APC), particularly dendritic cells (DC), orchestrate early alloimmune responses by activating recipient effector T cells. Employing a targeted approach, we investigated the impact of donor-derived conventional DC (cDC) and APC on the immunogenicity of skin and skin-containing VCA grafts, using mouse models of skin and hind limb transplantation.
By post-transplantation day 6, skin grafts demonstrated severe rejections, characterized by predominance of recipient CD4 T cells. In contrast, hind limb grafts showed moderate rejection, primarily infiltrated by CD8 T cells. While donor depletion of cDC and APC reduced frequencies, maturation, and activation of DC in all analysed tissues of skin transplant recipients, reduction in DC activities was only observed in the spleen of hind limb recipients. Donor cDC and APC depletion did not impact all lymphocyte compartments but significantly affected CD8 T cells and activated CD4 T in lymph nodes of skin recipients. Moreover, both donor APC and cDC depletion attenuated the Th17 immune response, evident by significantly reduced Th17 (CD4+IL-17+) cells in the spleen of skin recipients and reduced levels of IL-17E and lymphotoxin-α in the serum samples of both skin and hind limb recipients. In conclusion, our findings underscore the highly immunogenic nature of skin component in VCA. The depletion of donor APC and cDC mitigates the immunogenicity of skin grafts while exerting minimal impact on VCA.

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