Hepatic Stellate Cells Improve Engraftment of Human Primary Hepatocytes: A Preclinical Transplantation Study in an Animal Model.

Human hepatocytes are used for liver cell therapy, but the small number of engrafting cells limits the benefit of cell transplantation. We tested whether cotransplantation of hepatocytes with hepatic stellate cells (HSCs) could improve hepatocyte engraftment in vivo. Human primary hepatocytes were transplanted into SCID mice either alone or in a mixture with HSCs (quiescent or after culture activation) or LX-2 cells (ratio 20:1).

Adult human liver mesenchymal stem/progenitor cells participate in mouse liver regeneration after hepatectomy.

The advances in stem cell science have promoted research on their use in liver regenerative medicine. Beyond the demonstration of their ability to display metabolic functions in vitro, candidate cells should demonstrate achievable in situ differentiation and ability to participate to liver repopulation. In this work, we studied the in vivo behavior of adult liver mesenchymal stem/progenitor cells (ADHLSCs) after transplantation into immunodeficient mice.

Adult-derived human liver progenitor cells in long-term culture maintain appropriate gatekeeper mechanisms against transformation.

The use of human liver progenitor cells in the development of clinical cell therapy depends on their constant availability and unaltered properties during culture. The present study investigates the effects of long-term in vitro culture on the specific characteristics of these cells and on their genetic stability. Adult-derived human liver progenitor cells (ADHLPCs) were isolated from 12 donors and cultured until senescence and cell death.

In vitro differentiated adult human liver progenitor cells display mature hepatic metabolic functions: a potential tool for in vitro pharmacotoxicological testing.

The potential use of stem/progenitor cells as alternative cell sources to mature hepatocytes remains basically dependent on their ability to exhibit some, if not all, the metabolic liver functions. In the current study, four major liver functions were investigated in adult derived human liver stem/progenitor cell (ADHLSCs) populations submitted to in vitro hepatogenic differentiation: gluconeogenesis, ammonia detoxification, and activity of phase I and phase II drug-metabolizing enzymes. These acquired hepatic activities were compared to those of primary adult human hepatocytes, the standard reference.

Adult-derived human liver mesenchymal-like cells as a potential progenitor reservoir of hepatocytes?

It is currently accepted that adult tissues may develop and maintain their own stem cell pools. Because of their higher safety profile, adult stem cells may represent an ideal candidate cell source to be used for liver cell therapies. We therefore evaluated the differentiation potential of mesenchymal-like cells isolated from adult human livers.

Epithelial cells with hepatobiliary phenotype: is it another stem cell candidate for healthy adult human liver?

Aim: To investigate the presence and role of liver epithelial cells in the healthy human adult liver.

Methods: Fifteen days after human hepatocyte primary culture, epithelial like cells emerged and started proliferating. Cell colonies were isolated and subcultured for more than 160 d under specific culture conditions.