Today Agnes Klara Böhm successfully defended her doctoral thesis entitled "Multidimensional analysis of different decellularization methods for diaphragmatic extracellular matrices in a murine model" summa cum laude!

Congratulations !

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.

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.

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.

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.

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.

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.

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!