1. Development of bioengineered xenogeneic decellularized humanized liver for the development of extracorporeal liver for the treatment of acute liver failure

Abstract

Background and Aims: Acute as well as chronic liver failures are major fatal problems, which lead up to 60–80% mortality every year. In acute condition, systemic inflammation and accumulation of toxic compounds (ammonia) in liver results in multi-organ failure which leads to hepatic encephalopathy. Liver transplantation is limited due to timely unavailability of enough donors, post-transplantation complications and high cost involvement. The present study demonstrates a promising strategy of using bioartificial extracorporeal liver support system prepared through decellularization and repopulation of xenogenic liver with human hepatic progenitor cells (hHPCs). Methods: Xenogenic liver was decellularized by perfusion method using retrograde change of detergents and other chemicals. Removal of nuclear components, retention of ECM and vascular integrity of whole decellularized liver was identified. DiD-labeled hHPCs were infused to identify the cells distribution and engraftment efficiency. Repopulation of hHPCs within the decellularized liver scaffold was determined by SEM analysis whereas the functional activity of repopulated cells was determined by ammonia detoxification experiment by urea quantification. Results: The decellularized liver vascular network was able to withstand fluid flow that entered through a central inlet vessel, branched into an extensive capillary bed, and coalesced into a single outlet vessel. Repopulated hHPCs showed homogeneous distribution within the decellularized liver scaffold showing defined vascular tree with multiple branching and residual niches of proliferating cells. Ammonia detoxification showed the functional activity and future applicability of repopulated humanized liver scaffold as extra-corporeal natural organ support system. Conclusions: This study demonstrate an innovative technology for bioengineering humanized extra- corporeal liver system as better approach for ammonia detoxification as temporary support to the failing liver. The authors have none to declare.