Engineering an endocrine Neo-Pancreas by repopulation of a decellularized rat pancreas with islets of Langerhans

Decellularization of pancreata and repopulation of these non-immunogenic matrices with islets and endothelial cells could provide transplantable, endocrine Neo- Pancreata. In this study, rat pancreata were perfusion decellularized and repopulated with intact islets, comparing three perfusion routes (Artery, Portal Vein, Pancreatic Duct). Decellularization effectively removed all cellular components but conserved the pancreas specific extracellular matrix. Digital subtraction angiography of the matrices showed a conserved integrity of the decellularized vascular system but a contrast emersion into the parenchyma via the decellularized pancreatic duct. Islets infused via the pancreatic duct leaked from the ductular system into the peri- ductular decellularized space despite their magnitude. TUNEL staining and Glucose stimulated insulin secretion revealed that islets were viable and functional after the process. We present the first available protocol for perfusion decellularization of rat pancreata via three different perfusion routes. Furthermore, we provide first proof-of-concept for the repopulation of the decellularized rat pancreata with functional islets of Langerhans. The presented technique can serve as a bioengineering platform to generate implantable and functional endocrine Neo-Pancreata

Validation of risk scores for allograft failure after liver transplantation in Germany: a retrospective cohort analysis

A growing number of clinical risk scores have been proposed to predict allograft failure after liver transplantation. However, validation of currently available scores in the Eurotransplant region is still lacking. We aimed to analyze all clinically relevant donor and recipient risk scores on a large German liver transplantation data set and performed a retrospective cohort analysis of liver transplantations performed at the Charité-Universitätsmedizin Berlin from January 2007 until December 2021 with organs from donation after brain death. We analyzed 9 previously published scores in 906 liver transplantations [Eurotransplant donor risk index (ET-DRI/DRI), donor age and model for end-stage liver disease (D-MELD), balance of risk (BAR), early allograft dysfunction (EAD), model for early allograft function (MEAF), liver graft assessment following transplantation (L-GrAFT7), early allograft failure simplified estimation (EASE), and a score by Rhu and colleagues). The EASE score had the best predictive value for 3-month, 6-month, and 12-month graft survival with a c-statistic of 0.8, 0.77, and 0.78, respectively. In subgroup analyses, the EASE score was suited best for male recipients with a high-MELD (>25) and an EAD organ. Scores only based on pretransplant data performed worse compared to scores including postoperative data (eg, ET-DRI vs. EAD, p<0.001 at 3-month graft survival). Out of these, the BAR score performed best with a c-statistic of 0.6. This a comprehensive comparison of the clinical utility of risk scores after liver transplantation. The EASE score sufficiently predicted 12-month graft and patient survival. Despite a relatively complex calculation, the EASE score provides significant prognostic value for patients and health care professionals in the Eurotransplant region

FIRE-9 - PORT / AIO-KRK-0418: a prospective, randomized, open, multicenter Phase III trial to investigate the efficacy of adjuvant/additive chemotherapy in patients with definitely-treated metastatic colorectal cancer

BACKGROUND: Additive/adjuvant chemotherapy as concept after local treatment of colorectal metastases has not been proven to be successful by phase III trials. Accordingly, a standard of care to improve relapse rates and long-term survival is not established and adjuvant chemotherapy cannot be recommended as a standard therapy due to limited evidence in literature. The PORT trial aims to generate evidence that post-resection/ablation/radiation chemotherapy improves the survival in patients with metastatic colorectal cancer. METHODS: Patients to be included into this trial must have synchronous or metachronous metastases of colorectal cancer-either resected (R0 or R1) and/or effectively treated by ablation or radiation within 3-10 weeks before randomization-and have the primary tumor resected, without radiographic evidence of active metastatic disease at study entry. The primary endpoint of the trial is progression-free survival after 24 months, secondary endpoints include overall survival, safety, quality of life, treatments (including efficacy) beyond study participation, translational endpoints, and others. One arm of the study comprising 2/3 of the population will be treated for 6 months with modified FOLFOXIRI or modified FOLFOX6 (investigator´s choice, depending on the performance status of the patients but determined before randomization), while the other arm (1/3 of the population) will be observed and undergo scheduled follow-up computed tomography scans according to the interventional arm. DISCUSSION: Optimal oncological management after removal of colorectal metastases is unclear. The PORT trial aims to generate evidence that additive/adjuvant chemotherapy after definitive treatment of colorectal metastases improves progression free and overall survival in patients with colorectal cancer. TRIAL REGISTRATION: This study is registered with clinicaltrials.gov ( NCT05008809 ) and EudraCT (2020-006,144-18)

Tracking of primary human hepatocytes with clinical MRI: Initial results with Tat-peptide modified superparamagnetic iron oxide particles

The transplantation of primary human hepatocytes is a promising approach in the treatment of specific liver diseases. However, little is known about the fate of the cells following application. Magnetic resonance imaging ( MRI) could enable real- time tracking and long- term detection of transplanted hepatocytes. The use of superparamagnetic iron oxide particles as cellular contrast agents should allow for the non- invasive detection of labelled cells on high- resolution magnetic resonance images. Experiments were performed on primary human hepatocytes to transfer the method of detecting labelled cells via clinical MRI into human hepatocyte transplantation. For labelling, Tat- peptide modified nano- sized superparamagnetic MagForce particles were used. Cells were investigated via a clinical MR scanner at 3.0 Tesla and the particle uptake within single hepatocytes was estimated using microscopic examinations. The labelled primary human hepatocytes were clearly detectable by MRI, proving the feasibility of this new concept. Therefore, this method is a useful tool to investigate the effects of human hepatocyte transplantation and to improve safety aspects of this method. ( Int J Artif Organs 2008; 31: 252- 7

Tracking of Primary Human Hepatocytes with Clinical MRI: Initial Results with Tat-Peptide Modified Superparamagnetic Iron Oxide Particles

The transplantation of primary human hepatocytes is a promising approach in the treatment of specific liver diseases. However, little is known about the fate of the cells following application. Magnetic resonance imaging ( MRI) could enable real- time tracking and long- term detection of transplanted hepatocytes. The use of superparamagnetic iron oxide particles as cellular contrast agents should allow for the non- invasive detection of labelled cells on high- resolution magnetic resonance images. Experiments were performed on primary human hepatocytes to transfer the method of detecting labelled cells via clinical MRI into human hepatocyte transplantation. For labelling, Tat- peptide modified nano- sized superparamagnetic MagForce particles were used. Cells were investigated via a clinical MR scanner at 3.0 Tesla and the particle uptake within single hepatocytes was estimated using microscopic examinations. The labelled primary human hepatocytes were clearly detectable by MRI, proving the feasibility of this new concept. Therefore, this method is a useful tool to investigate the effects of human hepatocyte transplantation and to improve safety aspects of this method. ( Int J Artif Organs 2008; 31: 252- 7