New approaches to construction of liver tissue in vivo: Less invasive techniques and progenitor cells.

Background: The selective proliferation of transplanted hepatocytes by providing a growth stimulus, such as partial hepatectomy, concomitant with hepatic irradiation (HIR) that can suppress proliferation of hepatocytes was reported. We have conducted experiments which focus on I) less invasive techniques and II) progenitor cells. Methods: I) Dipeptidyl-peptidase IV (DPPIV)-F344 or Gunn rats received partial HIR (only 30% of liver) and portal vein branch ligation (PVBL) of one lobe, followed by intrasplenic hepatocyte transplantation at 1x10⁷. II) After partial HIR+PVBL, various stem cells were transplanted, i.e., small hepatocytes (SHs) or adipose derived mesenchymal stem cells (ADMSCs). Results: I) Sixteen weeks later, the donor cells constituted more than 70% of the hepatocytes of the irradiated lobe, showing connexin 32, PCK-1 and glycogen storage. Moreover, the serum bilirubin level decreased significantly in Gunn rats. II) SHs grew more quickly than hepatocytes, and after 8 weeks, around 40% of host hepatocytes were replaced with SHs. Although ADMSCs were engrafted, their proliferation was not observed. Conclusion: HIR can be given to a selective lobe of liver and is a low-invasive means for transplanted hepatocytes to proliferate combined with PVBL. Even a smaller number of SHs can construct liver tissue with their prevailing proliferative ability. Loss of proliferation of extra-hepatic stem cell infers tissue specificity and differentiation in vitro before transplantation would be needed for ADMSCs to get proliferated.