A novel integration of mesenchymal stromal cell bioreactors with liver normothermic machine perfusion has shown promising results for reducing ischemia/reperfusion injury.
The findings from this proof-of-concept study demonstrate the potential of mesenchymal stromal cells (MSCs) to significantly improve liver viability and function during transplantation procedures. Conducted by researchers from the University of Padua and Fondazione Ca' Granda Ospedale Maggiore Policlinico, the research successfully coupled MSC bioreactors with normothermic machine perfusion (NMP) systems, offering new horizons for liver transplant outcomes.
Normothermic machine perfusion is recognized for its ability to preserve and potentially improve the quality of livers before transplantation, but challenges remain, particularly related to the ischemia/reperfusion injury often encountered. This injury can affect livers from extended criteria donors, limiting their usability. The recent study sought to explore the utilization of MSCs as therapeutic agents during this process.
Over the course of the study, which included several phases of experiments on rat and porcine models, researchers developed and tested novel perfusion systems integrated with MSC-cultured bioreactors. Initial assessments confirmed MSCs retained their stem properties and exhibited enhanced secretory activity when influenced by liver perfusates, highlighting their compatibility and effectiveness during NMP procedures.
The methodology featured three sequential work packages, starting with laboratory-based liverless perfusion to establish the MSC-bioreactor's functionality. Following this, rats underwent NMP with perfused livers either with MSCs or standard setups. Results clearly indicated enhanced liver performance with the bioreactor-based methods, including reductions in markers of liver damage and inflammation, alongside notable increases in bile production.
Through the integration of MSC-bioreactors, the study showcases several benefits: fewer perfusion-related injuries occurred, and all machines operated smoothly without issues. Researchers noted, "No machine failure and perfusion-related injury were observed," as they emphasized the robustness of the platform.
Shifting to applications on larger animals, the research successfully translated the small animal insights to porcine livers, confirming both the feasibility and safety of this integrated approach for clinical use. This pivotal research advances the current knowledge on how MSCs can provide protective benefits against ischemia and supports their wider application within transplantation settings.
The findings collectively herald the MSC-based liver NMP platform as significant, providing grounds for future investigations. By mitigating the effects of ischemia/reperfusion before liver transplants, this research opens pathways for enhancing transplant organ viability, potentially increasing the number of suitable organs available for patients. Further studies are necessary to solidify these results and tailor protocols for human application.
Overall, the application of MSCs during normothermic perfusion has the potential to revolutionize how transplantable livers are treated, leading to improved outcomes for patients awaiting organ transplants.