Normothermic machine perfusion of the liver (NMP-L) has been used for organ preservation and viability testing of donor livers. Although previously proposed, delivery of cellular therapy to donor livers using NMP-L has not yet been described. A body of pre-clinical work with multi-potent adult progenitor cells (MAPC) suggests their potential as an anti-inflammatory therapy in solid organ transplantation and may increase organ tolerance.

Six rejected human livers (2 donors following brain death, DBD, and 4 from donors following circulatory death, DCD) were perfused for 6 hours at 37 degrees using the Liver Assist NMP device (Organ Assist, Groningen). 50,000,000 labelled MAPC (Multistem, Athersys Inc., Cleveland, Ohio) were infused directly into the right lobe via the hepatic artery (HA, n=3) or portal vein (PV, n=3) during the perfusion. Vascular flow parameters were recorded, perfusate biochemistry analysed and liver viability was assessed using an established protocol. Tissue samples were taken for histological analysis before and after cellular infusion.

The cells, in 50ml of vehicle, were infused over 20 mins into the right lobe via the right HA or right PV branch (1 DBD and 2 DCD in each group) initially after 4 hours of perfusion (n=2, first HA and PV infusion). Vascular flow characteristics were not negatively affected by the infusion, therefore subsequent infusions were performed after 1 hour (n=4, 2 HA and PV infusions). Fluorescent microscopy demonstrated engraftment of the MAPC within 1 hour of infusion and cells were still present 5 hours after infusion. MAPC were never identified in the left lobe at any time atfer the infusion. All three HA infusions resulted in right lobar engraftment of MAPC, which were able to cross the sinusoidal endothelium. Cellular engraftment following PV infusion was only evident in the perfusion of one viable donor liver.

NMP-L can be used to infuse MAPC directly into human donor livers. The HA infusion route resulted in consistent cellular engraftment. This technique could overcome the shortcomings of systemic infusions, delivering cellular therapy to the target organ prior to implantation and the subsequent exposure to the recipient immune cell population.

CITATION INFORMATION: Laing R, Stubblefield S, Ricky B, Barnaby S, Alfaifi M, Ting A, Mirza D, Newsome P, Mergental H, Afford S. The Delivery of Stem Cell Therapy to Extended Criteria Donor Human Livers Using Normothermic Machine Perfusion. Am J Transplant. 2017;17 (suppl 3).

« Back to 2017 American Transplant Congress