LAUSR

Transplantation of porcine hepatocytes for the treatment of humans acute and chronic liver diseases is considered an alternative to transplantation treatment. Especially, a bioartificial liver using porcine patocytes has the potential to facilitate liver transplantation for pati with acute-on-chronic liver failure. However, the use of porcine primary h tocytes is limited by their low survivability under in vitro culture systems complicated methods of isolation. To address this concern, we attempte generate induced hepatocyte-like cells from bone marrow mesenchy stem cells (BM-MSCs) derived from an α1, 3-Galactosyltransferase kn out (GalT KO) pig by transfecting three hepatocyte transcription fac (HNF1A, HNF4A, and FOXA3) and an additional small molecule suc A83-01, an inhibitor of TGF-ß receptor. BM-MSCs derived from the G KO pig could be used to minimize immune rejection in xenotransplanta in the future. The ratio of BM-MSCsand the three lentiviral vectorswasm tained at MOI =1 and at one day post infection, theywere cultured in a h tocyte culture medium with or without 2 μM A83-01 for 4 weeks. Por induced hepatocyte-like cells (piHeps) were observed at a low freque from 1 week onwards, regardless of A83-01; however, the presenc A83-01 increased the colony number of piHeps. Up to 4 weeks, piH maintained A83-01 treatment group but not without A83-01. qPCR ana of liver-specific genes such as albumin and transferrin genes revealed A83-01 improved the expression of these genes in the piHeps. Not A83-01 treatment could induce the activation of endogenic genes (pHNF pHNF4A, and pFOXA3) in piHeps, as indicated by qPCR results. These sults suggest that piHeps could be generated using the threementioned tors, although at a low efficiency, and that A83-01 could improve efficiency of piHep generation by the inhibition of epithelial-to-mesenchy transition. These findings provide valuable information in the field of tran tional liver research and testing cells for the development of a bioartificial system and novel pharmaceuticals. This work was supported by the Cooperative Research Program for riculture Science & Technology Development (Project No. PJ011002 RDA, Republic of Korea.