Neural trans-differentiation potential of hepatic oval cells in the neonatal mouse brain

Although the existence of the hepatic oval cell (HOC), the liver stem cell has been known for almost 70 years, little is known about the potential for this adult stem cell to trans-differentiate into cells of other tissues. While their origin remains enigmatic, HOCs share many similarities with hematopoietic stem cells. Recent studies have revealed that a small percentage of HOCs can arise from a bone marrow-derived stem cell source. Here we report that, like bone marrow stem cells, HOCs can survive transplantation to the neonatal mouse brain and show signs of trans-differentiation by adopting the morphology and antigenic phenotype of both macro- and microglia cells. Trans-differentiated microglia cells were functional, showing active phagocytosis when cotransplanted with latex microbeads in vivo. In addition to glial markers, a small number of transplanted HOCs were immunopositive for neuronal markers, but displayed ambiguous phenotype, making their characterization difficult.