Proteomic profiling of colorectal liver metastases reveals histopathological response-specific molecular signatures of chemotherapy efficacy.
In: Regenerative Medicine |Oncology
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The study "Proteomic profiling of colorectal liver metastases reveals histopathological response-specific molecular signatures of chemotherapy efficacy" explores proteomic differences in colorectal liver metastases (CRLM) to understand chemoresistance and identify potential biomarkers for treatment response.

33 tissue samples from 31 patients were analyzed, including patients treated preoperatively with platinum-based chemotherapy, non-platinum-based chemotherapy, or targeted therapies, as well as untreated patients. Tumors were classified into major (MR), partial (PR), or no response (NR) groups using histopathological criteria. Proteomic profiling was performed using label-free mass spectrometry (LFQ-MS).
Analysis identified 607 proteins with differential expression across response types. Responsive CRLM were enriched in pathways related to immune infiltration, extracellular matrix organization, complement activation, and apolipoprotein processes, reflecting distinct stromal and immune patterns. Non-responsive tumors showed reduced expression of proteins involved in mitochondrial translation.
These findings indicate that CRLM have distinct proteomic phenotypes associated with histopathological response, largely independent of chemotherapy type, providing a foundation for biomarker discovery to predict and monitor chemotherapy efficacy.

The paper is available in the March 2026 issue of Journal of Translational Medicine. Authors are A.K. Böhm, L.M. Skrip, D. Klein, F. Strobl, J.K. Wieland, A. Arnold, Y. Zhou, B. Papke, C. Sers, D.P. Modest, S. Moosburner, P.K. Haber, F. Krenzien, N. Raschzok, W. Schöning, D. Horst, T. Malinka, I. Sack, J. Pratschke, I.M. Sauer, and K.H. Hillebrandt.

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Virtual reality volumetric rendering versus cross-sectional imaging for pancreatic cancer resectability assessment
In: Digital Surgery |Oncology
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Our paper on "Virtual reality volumetric rendering versus cross-sectional imaging for pancreatic cancer resectability assessment: a pilot randomized controlled reader study" is available here. Authors are K. Eisenträger, K. Saribeyoglu, U. Fehrenbach, M. Felsenstein, L. Timmermann, P.L.M. Pereira, W. Schöning, B. Strücker, J. Pratschke, A. Pascher, T. Malinka, I.M. Sauer, H. Morgul, and M. Queisner.
This study evaluated whether virtual reality (VR) visualization of CT scans improves the assessment of pancreatic cancer resectability compared with conventional cross-sectional imaging (CSI) on 2D screens. Ten hepatopancreatobiliary surgeons assessed twelve CT cases using either VR volumetric rendering or standard CSI. Results showed that CSI outperformed VR. CSI achieved substantial inter-rater agreement (κ = 0.609), whereas VR showed only slight agreement (κ = 0.127). Diagnostic accuracy was also higher with CSI (84.7% vs. 79.7%), particularly for determining resectability (83.3% vs. 58.3%). Surgeons using VR reported lower confidence, while assessment time was similar between the two methods.
Overall, this preliminary study suggests that the tested VR visualization strategy performed worse than conventional imaging. However, previous research indicates that different or hybrid VR visualization approaches may still improve agreement, implying that the specific visualization method—rather than VR technology itself—determines clinical usefulness.

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Impact of Donor Age and Prolonged Warm Ischemia in Normothermic Machine Perfusion of Rat Livers
In: Regenerative Medicine |Transplantation
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The study "Impact of Donor Age and Prolonged Warm Ischemia in Normothermic Machine Perfusion of Rat Livers" published in Tissue Eng Part A investigated how donor age and circulatory death affect the viability of extended criteria donor (ECD) liver grafts using a rat normothermic machine perfusion (NMP) model. Livers from young (3-month) and older (12-month) rats were subjected to 30 minutes of warm ischemia followed by 3 or 6 hours of NMP. Functional parameters, metabolic markers, histology, and proteomics were analyzed.
Key findings include:
  • All grafts remained metabolically active, showing lactate clearance and bile production.
  • Older livers had more acidotic perfusate pH and increased necrosis after prolonged perfusion.
  • Younger livers exhibited higher transaminase release.
  • Proteomic analysis revealed age- and perfusion time-dependent changes in pathways related to mitochondrial damage, oxidative stress, and immune activation, which were not consistently detected by conventional viability markers.
The study suggests that histological and molecular assessments during NMP can better capture graft injury than standard markers, supporting tailored interventions to improve ECD graft quality and potentially expand their use in transplantation amidst organ shortages and an aging donor population.
Authors are A.S. Pietsch, L. Boerger, L. Padoan, K.A. Walter, J.M. Gassner, O. Klein O, L.A. Böhne, A. Arnold, D. Horst, I. Iske, K.H. Hillebrandt, F. Krenzien, J. Pratschke, I.M. Sauer, N. Raschzok, and S. Moosburner.

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Injured epithelial cell states impact kidney allograft survival after T-cell-mediated rejection
In: Transplantation |Regeneratve Medicine
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T-cell-mediated rejection (TCMR) remains a major cause of kidney transplant failure, despite being considered treatable. Its impact reflects a limited understanding of the underlying molecular mechanisms and their clinical consequences. To address this, we induced acute TCMR in mouse kidney transplants and profiled molecular changes using single-nucleus RNA sequencing (snRNA-seq), spatial transcriptomics and immunofluorescence. Results were compared with human snRNA-seq data from TCMR and stable allografts, as well as single-cell deconvolution analysis of bulk transcriptomic data from kidney transplant biopsies. Here we show that TCMR induces injured epithelial cell states in mouse kidney allografts, particularly in proximal tubules and thick ascending limbs. Spatial transcriptomics of these injured epithelial states demonstrated heterogeneous localization, interactions with immune cells and cellular microenvironments. Cross-species analysis confirmed similar severely injured epithelial states in human samples, whose abundances correlated with transplant survival and persisted despite TCMR resolution. Collectively, our results identify epithelial injury cell states as a determinant of outcome after TCMR.

The paper entitled "Injured epithelial cell states impact kidney allograft survival after T-cell-mediated rejection." by A.M. Pfefferkorn, L. Jahn, P.T. Gauthier, V.A. Kulow, J. Roeles, N. Müller-Bötticher, L.M.S. Gerhardt, J. Leiz, S. Sarfraz, I. Plumbom, R. Greite, S. Lovric, J. Gamrekelashvili, F. Limbourg, J. Schmitz, J.H. Bräsen, I. Scheffner, I.M. Sauer, F. Aigner, J. Altmüller, T. Conrad, W. Gwinner, N. Ishaque, M. Fähling, K.M. Schmidt-Ott, P.F. Halloran, M.I. Ashraf, and C. Hinze is available in the January 2026 issue of Nature Communications.

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Comparison of different decellularization protocols for porcine centrum tendineum diaphragmatis and diaphragmatic muscle
In: Regenerative Medicine
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The latest study "Comparison of different decellularization protocols for porcine centrum tendineum diaphragmatis and diaphragmatic muscle - a base for effective recellularization" published by B.F. Gaag, P. Tang, O. Klein, S. Moosburner, A.K. Böhm, T. Lohmann, J.K. Wieland, V. Contes, Y. Zhou, E. Keshi, L. Haderer, E. Metzler, V. Schöwel-Wolf, S. Spuler, J.C. Rückert, J. Pratschke, I.M. Sauer, M.N. Andreas, and K.H. Hillebrandt evaluated decellularization strategies for porcine diaphragm tissue to support the development of biocompatible scaffolds for diaphragmatic repair. Diaphragmatic dysfunction often requires reconstruction, but current materials have limitations such as poor biocompatibility and immune reactions. Decellularization aims to remove cells while preserving the extracellular matrix (ECM), enabling tissue engineering approaches.
Three protocols were compared:
P1: Detergent-enzymatic treatment adapted from murine diaphragm.
P2: A protocol designed for larger mammalian (human) diaphragm tissue.
P3: A protocol developed for porcine tendinous diaphragm.
All protocols significantly reduced DNA content, indicating effective removal of cellular material. Proteomic analysis identified 4,640 conserved proteins, including matrisomal proteins important for ECM structure. About 55% of the matrisomal fraction was consistently preserved across protocols. P3 preserved the most proteins, followed by P2 and P1; however, P3 did not fully meet current decellularization standards.
Overall, P1 and P2 provided effective ECM preservation while removing cellular components, with no clear superiority between them. The findings support further development of decellularized porcine diaphragm scaffolds for potential clinical application in diaphragm repair.
The paper was published in the January issue of the Journal of Biological Engineering.

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Assessing age and cold ischemia effects on liver tissue viscoelastic propertie
In: Transplantation |Regeneratve Medicine
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L.M. Skrip, L. Boerger, K.A. Walter, A. Arnold, L.A. Böhne, E. Keshi, A.S. Pietsch, N. Raschzok, T.A. Auer, U. Fehrenbach, F. Krenzien, J. Pratschke, I.M. Sauer, J. Guo, J. Braun, M. Tzschätzsch, I. Sack, K.H. Hillebrandt, and S. Moosburner evaluated whether magnetic resonance elastography (MRE) can assess liver graft quality after normothermic machine perfusion (NMP) in the context of liver transplantation. Because of organ shortages, extended criteria donor livers are increasingly used, but factors such as older donor age and prolonged cold ischemia time (CIT) can impair graft quality.
Using a rat liver NMP model, 24 livers underwent 6 or 12 hours of cold ischemia followed by 6 hours of NMP. Ex vivo multifrequency MRE was used to measure liver viscoelastic properties, including the power-law exponent (α) and shear modulus (μ).
Results showed that all liver samples displayed predominantly viscous-fluid characteristics (α > 0.5). The highest α values were found in young livers with short CIT, indicating better tissue properties, while older livers with prolonged CIT had significantly lower α values, suggesting impaired viscoelasticity. Additionally, shear modulus was lowest in young livers with short CIT, distinguishing them from the other groups.
Overall, the findings indicate that extended cold ischemia and older donor age impair liver tissue mechanics even after NMP. MRE may serve as a complementary imaging tool alongside MRI and histological analysis to evaluate liver graft quality during machine perfusion.
The paper "Assessing age and cold ischemia effects on liver tissue viscoelastic properties: Implications for graft quality assessment with MRE during machine perfusion" is available in Journal of the Mechanical Behavior of Biomedical Materials 2026; 175: 107291.

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Overcoming the data barrier: transfer learning for 90-day mortality prediction in general surgery
In: Digital Surgery
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The study "Overcoming the data barrier: transfer learning for 90-day mortality prediction in general surgery - a retrospective multicenter development and comparison study" was published in the January issue of the International Surgery Journal by A. Winter, B. Pfitzner, R.P. van de Water, L. Faraj, C. Riepe, W.H. Hahn, F. Krenzien, C. Schineis, T. Malinka, W. Schöning, C. Denecke, B. Arnrich, K. Beyer, J. Pratschke J, I.M. Sauer, and M.M. Maurer.

This multicenter study investigated whether transfer learning (TL) can improve AI-based prediction of 90-day postoperative mortality in general surgery, where limited datasets often hinder the development of robust models.

Data from 14,922 patients undergoing esophageal, liver, pancreatic, or colorectal surgery across three tertiary centers (2015–2023) were analyzed using 85 preoperative variables. Large source neural network models were first trained, then fine-tuned for specific surgical procedures using transfer learning. These models were compared with conventional machine learning (ML) approaches and standard clinical risk scores.
Results showed that ML models already outperformed traditional risk scores (e.g., ASA and Charlson Comorbidity Index). Transfer learning further improved performance, particularly in predicting mortality for esophageal (+38% AUPRC), liver (+14%), and pancreatic surgery (+8%). Across all models, patient age and the Charlson Comorbidity Index were the most influential predictors.
Overall, the study demonstrates that transfer learning can significantly enhance AI model performance in surgical settings with limited data, offering a promising strategy for improving preoperative risk stratification and decision-making in general surgery.

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Lipocalin-2 modulates recipients alloimmune responses to the murine kidney transplants.
In: Transplantation
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"Lipocalin-2 modulates recipients alloimmune responses to the murine kidney transplants." was published by A.M. Pfefferkorn , R. Fritsche-Guenther, A. Kusch, H. Schwelberger, S. Liu, R. Klopfleisch, Y. Li, R. Catar, S. Liu, F. Aigner, J. Pratschke, I.M. Sauer, and M.I. Ashraf in the December Issue of Frontiers in Immunology 2025.

This study investigated the mechanisms behind the renoprotective effects of recombinant Lipocalin-2 (rLcn2) in kidney transplantation (KTx). Lipocalin-2 is known as an early biomarker for acute kidney injury, delayed graft function, and transplant rejection. Using a mouse kidney transplant model, researchers examined how rLcn2 affects immune responses after transplantation.
Treatment with rLcn2 (Lcn2:Siderophore:Fe³⁺ complex) significantly reduced T-cell activation and frequency, particularly effector memory T cells and their cytotoxic (CD8⁺) and helper (CD4⁺) subsets, in graft tissue, lymphoid organs, and blood by postoperative day 7. In graft-infiltrating CD8⁺ T cells, rLcn2 also reduced cytotoxic activity, including lower degranulation capacity and decreased interferon-γ and perforin expression, as well as fewer NKG2D⁺ activated cytotoxic T cells. Effects on innate immune cells were limited and selective, affecting only some neutrophils, macrophages, and NK cell subsets.
Importantly, rLcn2 did not influence inflammation or tissue injury in syngeneic (non-alloimmune) transplants, indicating that its protective effect is primarily through modulation of adaptive immune responses, particularly T-cell activity.
Overall, the findings suggest that rLcn2 improves kidney graft outcomes by selectively suppressing alloimmune T-cell responses rather than altering non-immune injury pathways.

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Privacy preserving federated learning for 90-day mortality prediction in colorectal surgery
In: Digital Surgery
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M.M. Maurer, B. Pfitzner, R.P. van de Water, L. Faraj, C. Riepe, D. Zuluaga, F. Krenzien, N. Raschzok, R. Siegel, C. Schineis, B. Arnrich, K. Beyer, J. Pratschke, I.M. Sauer, and A. Winter evaluated federated learning (FL) as a privacy-preserving approach for AI-based prediction of 90-day mortality after colorectal surgery. Limited data sharing between hospitals often restricts surgical AI development, and FL allows multicenter model training without transferring raw patient data. The study also assessed the effect of differential privacy (DP) on model performance.
Data from 2,959 patients undergoing elective colorectal surgery at three tertiary centers (2015–2021) were analyzed. Neural networks were trained locally at each center, using centralized data aggregation and distributed federated learning. Additional privacy protection was implemented using central and local differential privacy.
Results showed that federated learning performed similarly to centralized modeling, achieving comparable predictive accuracy (AUROC ~0.78 vs. 0.81). However, adding differential privacy reduced performance, with central DP causing moderate declines and local DP nearly eliminating predictive accuracy. Across models, the most influential predictors were patient age, blood parameters, and the Charlson Comorbidity Index.
Overall, the study demonstrates that federated learning can enable effective multicenter surgical AI models while preserving data privacy, though strong privacy mechanisms like differential privacy may significantly compromise model performance.

"Privacy preserving federated learning for 90-day mortality prediction in colorectal surgery: a multicenter retrospective development and comparison study" is available in International Journal of Surgery 2025;111(12):9065-9074

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Prototype of a Virtual Reality Simulator for Thyroidectomy: A Proof of Concept.
In: Digital Surgery
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The anatomical complexity of the thyroid region presents significant challenges in surgical training, particularly regarding the identification and preservation of the recurrent laryngeal nerve and parathyroid glands. We present a prototype of a virtual reality simulator designed to support thyroidectomy training by enabling the immersive, interactive exploration of CT-derived, deformable anatomical models in a photorealistic operating room environment. Structures not detectable in CT, such as nerves and glands, were manually integrated. The simulator was evaluated qualitatively by three surgeons using a structured questionnaire. Feedback indicated high usability, visual realism, and potential for improving anatomical recognition skills. Limitations include the absence of instrument interaction, haptic feedback, and full procedural simulation. This prototype demonstrates feasibility and outlines a clear development roadmap toward a high-fidelity, scalable training platform for endocrine surgery.

The paper "Prototype of a Virtual Reality Simulator for Thyroidectomy: A Proof of Concept." by K. Eisentraeger, E.M. Dobrindt, M. Queisner, C. Remde, I.M. Sauer, J. Pratschke, M. Mogl, F. Butz, and C. Müller-Debus was published in Cureus Journal of Medical Science. 2025;17(9):e92724

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Lipocalin-2 Restores Soluble Guanylyl Cyclase-Dependent Dilation of the Afferent Arteriole After Renal Transplantation or Ex Vivo Hypoxia/Reoxygenation in Mice
In: Transplantatiomn
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L. Zhao, M. Xu, A.M. Pfefferkorn, C. Erdogan, H. Schwelberger, P. Wang, P.H. Khedkar, M. Eigen, F.B. Lichtenberger, R. Catar, E.Y. Lai, F. Aigner, P.B. Persson, I.M. Sauer, A. Patzak, and M.I. Ashraf published the paper "Lipocalin-2 Restores Soluble Guanylyl Cyclase-Dependent Dilation of the Afferent Arteriole After Renal Transplantation or Ex Vivo Hypoxia/Reoxygenation in Mice" in Acta Physiologica 2025;241(8): e70077.

This study investigated whether iron-bound lipocalin-2 (holo-rLcn2) can restore soluble guanylyl cyclase (sGC)-mediated microvascular dilation in the kidney after hypoxia/reoxygenation (H/R) and kidney transplantation. Microvascular dysfunction is a key factor in ischemia/reperfusion injury, and sGC activators like cinaciguat lose efficacy after severe hypoxia.
Using isolated mouse afferent arterioles (AAs) and ex vivo kidney perfusion, the researchers tested vascular dilation following H/R and syngeneic kidney transplantation with short (30 min) or prolonged (5.5 h) cold ischemia.
  • Key findings include:
  • H/R impaired AA dilation, which was preserved by holo-rLcn2 but not by iron-free apo-rLcn2.
  • The protective effect of holo-rLcn2 was iron-dependent, as it was reversed by the iron chelator deferoxamine.
  • Kidney transplants exhibited reduced AA dilation, particularly after prolonged ischemia, but holo-rLcn2 treatment restored dilation to levels seen with shorter ischemia.
  • Ex vivo kidney perfusion confirmed that holo-rLcn2 enhanced cinaciguat-induced vascular relaxation at the organ level.
Overall, the study identifies a novel role for iron-bound rLcn2 in preserving renal vascular function after ischemic injury and transplantation, likely by maintaining iron-dependent vascular mechanisms.

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New Book: Virtual participation, real involvement – Transformative technologies for a more inclusive society
In: Digital Surgery
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Virtual reality (VR) and augmented reality (AR) are among the fastest-growing technologies of the 21st century. They also open up enormous opportunities for social integration: through cultural and educational offerings, through networked digital interaction spaces, or as a means of promoting citizen participation. The contributions in this volume present a wide range of application scenarios for VR and AR in the fields of education, health and public space. They demonstrate in a practical way how society, but also companies, can benefit from expanding their technological skills and taking diversity aspects into account. After all, genuine participation is only possible through a sustainable, transdisciplinary and citizen science approach.

Our book chapter ‘Human-Centred Design of Mixed Reality Applications in Medical Education – GreifbAR’ is now available in open access. Authors are Robert Luzsa, Moritz Queisner, Christopher Remde, Igor Sauer, Nadia Robertini and Susanne Mayr.

As part of the BMBF-funded project ‘Tangible Reality – Skilful Interaction of User Hands and Fingers with Real Tools in Mixed Reality Worlds’, we investigated how XR technology can be integrated into medical education. The chapter presents an interdisciplinary, XR-based training system for surgical knot tying. It describes key design principles and experiences from development and evaluation. In addition, it proposes a model for the human-centred design of comparable training applications that can also support other projects.

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90-Day Mortality Prediction in Elective Visceral Surgery Using Machine Learning
In: Digital Surgery |Oncology
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Our paper, "90-Day Mortality Prediction in Elective Visceral Surgery Using Machine Learning: A Retrospective Multicenter Development, Validation, and Comparison Study" has been published online ahead of print in the International Journal of Surgery.
Authors are C. Riepe, R. van de Water, A. Winter, B. Pfitzner, L. Faraj, R. Ahlborn, M. Schulze, D. Zuluaga, C. Schineis, K. Beyer, J. Pratschke, B. Arnrich, I.M. Sauer, and M.M. Maurer

Machine Learning (ML) is increasingly being adopted in biomedical research, however, its potential for outcome prediction in visceral surgery remains uncertain. This study compares the potential of ML methods for preoperative 90-day mortality (90DM) prediction of an aggregated multi-organ approach to conventional scoring systems and individual organ models.

This retrospective cohort study enrolled patients undergoing major elective visceral surgery between 2014 and 2022 across two tertiary centers. Multiple ML models for preoperative 90DM prediction were trained, externally validated and benchmarked against the American Society of Anesthesiologists (ASA) score and revised Charlson Comorbidity Index (rCCI). Areas under the receiver operating characteristic (AUROC) and precision recall curves (AUPRC) including standard deviations were calculated. Additionally, individual models for esophageal, gastric, intestinal, liver, and pancreatic surgery were developed and compared to an aggregated approach. A total of 7,711 cases encompassing 78 features were included. Overall 90DM was 4% (n = 309). An XBoost classifier demonstrated the best performance and high robustness following external validation (AUROC: 0.86 [0.01]; AUPRC: 0.2 [0.04]). All models outperformed the ASA score (AUROC: 0.72; AUPRC: 0.08) and rCCI (AUROC: 0.81; AUPRC: 0.11). rCCI, patient age and C-reactive protein emerged as most decisive model weights. Models for gastric (AUROC: 0.88 [0.13]; AUPRC: 0.24 [0.26]) and intestinal surgery (AUROC: 0.87 [0.05]; AUPRC: 0.17 [0.09]) revealed the highest organ-specific performances, while pancreatic surgery yielded the lowest results (AUROC: 0.66 [0.08]; AUPRC: 0.22 [0.12]). A combined multi-organ approach (AUROC: 0.84 [0.04]; AUPRC: 0.21 [0.06]) demonstrated superiority over the weighted average across all organ-specific models (AUROC: 0.82 [0.07]; AUPRC: 0.2 [0.13]).

ML offers robust preoperative risk stratification for 90DM in elective visceral surgery. Leveraging training across multi-organ cohorts may improve accuracy and robustness compared to organ-specific models. Prospective studies are needed to confirm the potential of ML in surgical outcome prediction.

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Michael Tummings | Human Insights
In: Transplantation
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Michael Tummings – Artist in Residence @ Experimental Surgery – has released his latest book, Human Insights.

In this powerful work, Tummings turns his lens toward the operating theatre, capturing intimate moments of surgical intervention. His photographs explore the human body not as an object of clinical analysis, but as a site of vulnerability, resilience, and transformation. As noted by Jörg Christian Tonn, Tummings' work "reveals the mysteries of the body," offering entirely new perspectives on physical existence and the role of modern medicine.

With the consent of both patients and surgical teams of several university hospitals, Tummings was granted rare access to document procedures involving organ implants and artificial prostheses. The resulting imagery bridges the worlds of art and science, bringing us face-to-face with the beauty of the human body—beyond the rational and dissecting eye.

Human Insights invites viewers to reconsider how we see ourselves and our bodies, especially in moments of repair and healing.

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Sparse camera volumetric video applications
In: Digital Surgery
The paper "Sparse camera volumetric video applications. A comparison of visual fidelity, user experience, and adaptability" is available open access in Frontiers in Signal Processing.
Authors are Christopher Remde, Igor M. Sauer, and Moritz Queisner.

Volumetric video production in commercial studios is predominantly produced using a multi-view stereo process that relies on a high two-digit number of cameras to capture a scene. Due to the hardware requirements and associated processing costs, this workflow is resource-intensive and expensive, making it unattainable for creators and researchers with smaller budgets. Low-cost volumetric video systems using RGBD cameras offer an affordable alternative. As these small, mobile systems are a relatively new technology, the available software applications vary in terms of workflow and image quality. In this paper we provide an overview of the technical capabilities of sparse camera volumetric video capture applications and assess their visual fidelity and workflow.

We selected volumetric video applications that are publicly available, support capture with multiple Microsoft Azure Kinect cameras and run on consumer-grade computer hardware. We compared the features, usability, and workflow of each application and benchmarked them in five different scenarios. Based on the benchmark footage, we analyzed spatial calibration accuracy, artifact occurrence and conducted a subjective perception study with 19 participants from a game design study program to assess the visual fidelity of the captures.

We evaluated three applications, Depthkit Studio, LiveScan3D and VolumetricCapture. We found Depthkit Studio to provide the best experience for novel users, while LiveScan3D and VolumetricCapture require advanced technical knowledge to be operated. The footage captured by Depthkit Studio showed the least amount of artifacts by a larger margin, followed by LiveScan3D and VolumetricCapture. These findings were confirmed by the participants who preferred Depthkit Studio over LiveScan3D and VolumetricCapture. Based on the results, we recommend Depthkit Studio for the highest fidelity captures. LiveScan3D produces footage of only acceptable fidelity but is the only candidate that is available as open-source software. We therefore recommend it as a platform for research and experimentation. Due to the lower fidelity and high setup complexity, we recommend VolumetricCapture only for specific use-cases where its ability to handle a high number of sensors in a large capture volume is required.
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Gender-based variations in surgical management of colorectal liver metastases
In: Oncology
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BMC Cancer published the paper "Gender-based variations in surgical management of colorectal liver metastases: comprehensive analysis". Authors are Pia F. Koch, Kristina Ludwig, Karl H. Hillebrandt, Hannes Freitag, Moritz Blank, Sebastian Knitter, Dominik P. Modest, Felix Krenzien, Georg Lurje, Wenzel Schöning, Johann Pratschke, Igor M. Sauer, Simon Moosburner, and Nathanael Raschzok.

Colorectal cancer with liver metastasis affects both men and women. However, therapeutic strategies and long-term outcomes could be influenced by patients' sex, due to variations in tumour biology, lifestyle, and dietary habits. By conducting a comprehensive comparative analysis, this study aims to detail differences in tumour characteristics, postoperative complications, recurrence rates, and survival outcomes between sexes.
We performed a Single-centre retrospective analysis between 2010 and 2022 of all patients undergoing liver surgery for colorectal liver metastases (CRLM) at the Department of Surgery, Charité- Universitätsmedizin Berlin. Patients were stratified by sex. Statistical analysis was performed using RV4.2.We analysed 642 patients who underwent hepatic resections for CRLM. Baseline patient characteristics were comparable between sexes: However, significant differences (p < 0.001) were noted in body mass index (BMI), with females exhibiting lower BMIs (median BMI in females: 23.7 kg/m² vs. males: 26.5 kg/m²). Primary tumour locations varied significantly (p = 0.008), with females presenting more sigmoid colon tumours (37%), while males predominantly had rectal tumours (35%). RAS mutation rates were higher in females (54%) than males (34%, p = 0.005). A higher prevalence of bilobar metastases were evident in men (62%, p = 0.011), yet surgical techniques and complications showed comparable distributions. The time for resection was longer in males (median 304 min vs. 290 min in females); however, conversion to open surgery took place more often in females (5.2% vs. 2.3% in males). Postoperative complications and survival rates showed no significant differences by patients' sex.
Distinct sex-related patterns in tumour characteristics and postoperative outcomes in patients with CRLM were observed, emphasizing the need for further investigations to understand and address gender-based disparities for more personalized clinical management in the future.

The paper is available open access here.

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Cytokine-armed vaccinia virus promotes cytotoxicity towards pancreatic carcinoma cells
In: Oncology
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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 is available open access 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.

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Induced pluripotent stem cell (iPSC) line (EXSURGi001-A) from a patient homozygous for the p.Ala165Thr mutation in the MTARC1 gene
In: Oncology |Regenerative Medicine
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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.

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Extracellular NAD+ Response to Post-Hepatectomy Liver Failure: Bridging Preclinical and Clinical Findings
In: Oncology |Regenerative Medicine
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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.

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Viscoelastic properties of colorectal liver metastases reflect the tumour cell viability
In: Oncology
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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,

Tags: Publication,FOR 5628

Distinctive protein expression in elderly livers in a Sprague-Dawley rat model of normothermic ex vivo liver machine perfusion
In: Transplantation |Regenerative Medicine
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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.

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Thrombogenicity assessment of perfusable tissue engineered constructs: a systematic review
In: Regenerative Medicine |Transplantation
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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.

Tags: Publication

Quality assessment by bile composition in normothermic machine perfusion of rat livers
In: Transplantation |Regenerative Medicine
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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.

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A new bicornuate model of rat uterus transplantation
In: 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.

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Depletion of donor dendritic cells ameliorates immunogenicity of both skin and hind limb transplants
In: Transplantation
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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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