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.

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!

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.