Transplantation represents the treatment of choice for many end-stage diseases but is limited by the shortage of healthy donor organs. Ex situ normothermic machine perfusion (NMP) has the potential to extend the donor pool by facilitating the use of marginal quality organs such as those from donors after cardiac death (DCD) and extended criteria donors (ECD). NMP provides a platform for organ quality assessment but also offers the opportunity to treat and eventually regenerate organs during the perfusion process prior to transplantation. Due to their anti-inflammatory, immunomodulatory and regenerative capacity, mesenchymal stem cells (MSCs) are considered as an interesting tool in this model system. Only a limited number of studies have reported on the use of MSCs during ex situ machine perfusion so far with a focus on feasibility and safety aspects. At this point, no clinical benefits have been conclusively demonstrated, and studies with controlled transplantation set-ups are urgently warranted to elucidate favorable effects of MSCs in order to improve organs during ex situ machine perfusion.

The coronavirus disease 2019 (COVID-19) pandemic has changed life on a global scale. The numbers of transplantations have plummeted as a result of fear of disease transmission, recipient coronavirus disease 2019 infection, priority shift, and resource limitations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) complicates transplantation because donor testing, (re)allocation of limited resources, and recipient testing may exceed permissible ischemia times.

Introduction: Normothermic machine perfusion (NMP) has emerged as a promising tool for assessing kidney quality prior to transplantation; however, reliable biomarkers remain to be established. Methods: In this study, thirteen porcine kidneys were perfused for 24 h using an autologous leukocyte‐filtered whole blood‐based perfusate applying urine recirculation. Functional, biochemical, and morphological parameters were assessed to comprehensively evaluate kidney quality. Results: Stable hemodynamics, sustained urine output, and oxygen consumption rates indicated preserved kidney viability. Within two hours of perfusion, microperfusion in renal cortex and ureter improved significantly, as confirmed by near‐infrared, tissue hemoglobin, and oxygen saturation metrics. Morphological assessment revealed progressive injury localized in proximal tubular cells, marked by increased vacuolization, reduced microvilli density, and swollen mitochondria with protruding membranes. In contrast, the architecture of distal tubules and glomeruli remained intact. Biomarker analysis corroborated these findings, with KIM‐1 and IGFBP‐7 levels, two biomarkers predominantly expressed in proximal tubular cells, rising. Notably, overall OXPHOS capacity declined with perfusion duration, while ATP production efficiency remained stable. Histological grading, in concordance with real‐time confocal assessment, showed no significant alteration over time. Conclusion: This study provides a detailed phenotypical and bioenergetic profiling of kidney grafts over 24 h of NMP, demonstrating preserved kidney viability and function. The observed subcellular and molecular alterations, especially affecting the proximal tubules, were not reflected in frequently gathered metrics like hemodynamic flow, urine output, oxygen consumption, or lactate levels. Further studies are needed to confirm these findings and evaluate their clinical impact after transplantation.

Background: Normothermic machine perfusion (NMP) is increasingly used to assess liver grafts before transplantation. While viability assessment of the hepatocellular compartment has been widely adopted, viability assessment of the biliary compartment remains controversial due to the lack of reliable markers. Glutathione (GSH) plays a key role in bile formation and may serve as a marker for biliary viability. Thus, the present study aimed to investigate the suitability of GSH as a potential marker for biliary viability assessment during NMP. Methods: Between 2018 and 2021, livers undergoing NMP were included in the study. Bile samples were collected at 1 h, 6 h, and at the end of NMP, and then analyzed using enzyme‐linked immunosorbent assay (ELISA). Results were correlated with perfusion parameters and clinical outcomes. Results: 56 livers underwent NMP during the study period, of which 41 were successfully transplanted (73.2%). Within 1 year after transplantation, 19 patients (46.3%) developed biliary complications. 1‐year patient survival was 80.5% and 1‐year graft survival (death‐censored) was 94.6%. The GSH in transplanted livers showed a significant increase over time (Hour 1: 25.9 ± 31.2 μM vs. End: 108.7 ± 95.3 μM, p < 0.001) and significant inverse correlation with the occurrence of biliary complications after transplantation ( p < 0.05). GSH concentration at the first hour measurement was significantly lower in livers that were deemed non‐transplantable (11.2 μM vs. 25.9 μM, p = 0.006). Conclusions: Our data show an increase of GSH in bile during liver ex situ NMP. We found a negative correlation between GSH concentration and the development of biliary complications, suggesting GSH as a new marker for biliary viability assessment.