Liver Repopulation: A New Concept of Hepatocyte Transplantation

Abstract

Hepatocyte transplantation has been recognized as an alternative strategy for organ transplantation because the supply of donor livers is limited. However, in conventional hepatocyte transplantation, only 1%-10% of the liver replaced with transplanted hepatocytes. Recently a novel concept termed "liver repopulation" has been established, where the whole recipient liver can be replaced by a small number of donor hepatocytes. To induce liver repopulation, growth advantage of the donor hepatocytes against the host liver seems to be required according to the data of previous studies. Additionally, various cell sources, including bone marrow cells and other stem cells, could potentially be used as donor cells for liver repopulation. In this article, we discuss recent progress and future perspectives of this emerging technology.

Construction of liver tissue in vivo with preparative partial hepatic irradiation and growth stimulus: investigations of less invasive techniques and progenitor cells

“…However, it has not been prevalent as a standard therapeutic option, mainly because of the limited number of hepatocytes at one time and the shortage of transplantable primary hepatocytes (4,22). To overcome these hurdles, the methods for growth of transplanted hepatocytes in the recipient, or the development or availability of substitute for primary hepatocytes, such as xenogeneic hepatocytes, fetal hepatocytes, and hepatic stem cells/progenitor cells have been explored.…”

Stem Cell Therapy for Liver Disease: Parameters Governing the Success of Using Bone Marrow Mesenchymal Stem Cells

“…Carbon tetrachloride was dissolved in mineral oil at 10% concentration and administered to animals by gavage. Dosages between 0.2 and 0.4 mL CCl 4 /kg body wt were tested for hepatotoxicity and lethality. Transplants were performed at 24 hours after administration of CCl 4 .…”

“…A single donor could serve multiple recipients, and excess cells could be cryopreserved for future use. 4 However, studies have shown that less than 20%-30% of transplanted hepatocytes survive upon transplantation and that multiple transplantation procedures are required to achieve meaningful liver repopulation. 5 Furthermore, the procurement of transplantable hepatocytes is hampered by the paucity of cadaveric liver, the limited replicative potential, the concomitant loss of characteristic hepatic functions upon in vitro culture, and reduced numbers of viable and functional cells upon cryopreservation.…”

Liver transplantation for patients with human immunodeficiency virus and hepatitis C virus coinfection with special reference to hemophiliac recipients in Japan

“…Those questions and controversies await further research on liver regenerative medicine 28 In conclusion, to date in the recent literature, extrahepatic cells, especially BM cells, might contribute to injured liver repair but not in the normally regenerating liver. The mechanism by which extrahepatic cells express a liver-specific function, whether transdifferentiation or cell fusion, remains under debate.…”