Development of a scaled up liver device incorporating cryo-preserved pig liver micro-organs

Currently there is no effective therapy for most patients with fulminant or end stage liver disease. Pig liver micro-organs (LMOs), which preserve liver micro-architecture and ensure a maximal 150-200 μm distance from a source of nutrients and gases have been prepared and a method to cryo-preserve them has been developed. A new scaled-up extra-corporeal liver device termed aLIVE-H in which LMOs are exposed to liver-like hemodynamic conditions has also been developed. The purpose of this work is to test the safety and function of cryo-preserved LMOs and how the hemodynamic properties of the scaled up aLIVE device affect their function. Pig LMOs in aLIVE-H, transcribe albumin and Factor V at similar levels, irrespective of their position within the bioreactor, indicating that the hemodynamic features of the aLIVE-H device allow for homogeneous plasma distribution and proper function at different locations. Cryo-preserved LMOs transcribe albumin and Factor V at levels comparable to those transcribed by a normal pig liver. Connecting the aLIVE-H bioreactor to normal pigs did not affect key blood components and biochemical parameters. An extra-corporeal liver device aLIVE-H which imitates the hemodynamic and functional properties of the normal liver and incorporates cryo-preserved LMOs has been developed and characterized. aLIVE-H was found to perform key synthetic liver functions.