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.

The article „Solid fraction determines stiffness and viscosity in decellularized pancreatic tissues“ in Biomaterials Advances is now available online.
There is free access to a PDF of the article here until August 20, 2022!

The role of extracellular matrix (ECM) composition and turnover in mechano-signaling and the metamorphic fate of cells seeded into decellularized tissue can be elucidated by recent developments in non-invasive imaging and biotechnological analysis methods. Because these methods allow accurate quantification of the composition and structural integrity of the ECM, they can be critical in establishing standardized decellularization protocols. This study proposes quantification of the solid fraction, the single-component fraction and the viscoelasticity of decellularized pancreatic tissues using compact multifrequency magnetic resonance elastography (MRE) to assess the efficiency and quality of decellularization protocols. MRE of native and decellularized pancreatic tissues showed that viscoelasticity parameters depend according to a power law on the solid fraction of the decellularized matrix. The parameters can thus be used as highly sensitive markers of the mechanical integrity of soft tissues. Compact MRE allows consistent and noninvasive quantification of the viscoelastic properties of decellularized tissue. Such a method is urgently needed for the standardized monitoring of decellularization processes, evaluation of mechanical ECM properties, and quantification of the integrity of solid structural elements remaining in the decellularized tissue matrix.

Authors are Joachim Snellings, Eriselda Keshi, Peter Tang, Assal Daneshgar, Esther C. Willma, Luna Haderer, Oliver Klein, Felix Krenzien, Thomas Malink, Patrick Asbach, Johann Pratschke, Igor M. Sauer, Jürgen Braun, Ingolf Sack, and Karl Hillebrandt.

Our paper "VolumetricOR: A new Approach to Simulate Surgical Interventions in Virtual Reality for Training and Education" is available in the latest issue of Surgical Innovation.

Surgical training is primarily carried out through observation during assistance or on-site classes, by watching videos as well as by different formats of simulation. The simulation of physical presence in the operating theatre in virtual reality might complement these necessary experiences. A prerequisite is a new education concept for virtual classes that communicates the unique workflows and decision-making paths of surgical health professions (i.e. surgeons, anesthesiologists, and surgical assistants) in an authentic and immersive way. For this project, media scientists, designers and surgeons worked together to develop the foundations for new ways of conveying knowledge using virtual reality in surgery.
A technical workflow to record and present volumetric videos of surgical interventions in a photorealistic virtual operating room was developed. Situated in the virtual reality demonstrator called VolumetricOR, users can experience and navigate through surgical workflows as if they are physically present . The concept is compared with traditional video-based formats of digital simulation in surgical training.

VolumetricOR let trainees experience surgical action and workflows a) three-dimensionally, b) from any perspective and c) in real scale. This improves the linking of theoretical expertise and practical application of knowledge and shifts the learning experience from observation to participation.
Discussion: Volumetric training environments allow trainees to acquire procedural knowledge before going to the operating room and could improve the efficiency and quality of the learning and training process for professional staff by communicating techniques and workflows when the possibilities of training on-site are limited.

Authors are Moritz Queisner, Michael Pogorzhelskiy, Christopher Remde, Johann Pratschke, and Igor M. Sauer.

Priv,-Doz. Dr. med. Felix Krenzien and Dr. Jennifer Kirwan (Technologieplattform Metabolomik, Max-Delbrück-Centrum für Molekulare Medizin, Berlin) successfully applied for a grant within the Else Kröner Fresenius Stiftung funding line: Translational Research.

Recently, the molecule nicotinamide adenine dinucleotide (NAD) has attracted attention as it is involved in various important regulatory mechanisms, immune signaling, aging and regenerative processes. In this regard, it occupies key positions in many redox reactions of the body due to its role as a redox couple (NAD as an oxidized species and NADH as a reduced species). Consequently, NAD homeostasis (the maintenance of NAD in cells) is considered essential. The scientific consensus for many years was that the oxidized species resides exclusively in the intracellular milieu (iNAD). However, recent findings indicate that NAD also exists extracellularly (eNAD) and it is present in virtually all body fluids (from lymph to saliva to blood plasma). Based on these findings, precursors of NAD have recently been approved by the FDA and are commercially available. Measurement of eNAD in blood plasma is problematic due to its low concentration in the nanomolar range. However, quantifying eNAD plasma levels but also eNAD concentrations in cells is necessary to monitor the intake of NAD or its precursors and to adjust their dosage precisely.
The primary objective of this project is to validate, bioanalyze,and to document the assay for eNAD according to the ICH-M10 guidance document endorsed by the U. S. Food and Drug Administration (FDA). Adherence to the principles presented in this guideline should improve the quality and consistency of bioanalytical data, thereby supporting assay development and market approval. In addition, the assay will also be established for the measurement of intracellular NAD (iNAD), and validation of iNAD quantification will also be performed according to the guideline.

In the second part of the project, a clinical study will be conducted to determine whether the intake of nicotinamide riboside (precursor of NAD) leads to a change in eNAD and iNAD. Thus, the basis for an indication-dependent bioanalysis of the measurement of NAD will be developed to monitor the intake of NAD and its precursor or to adjust the dosage specifically on the basis of the quantification.