Plasticity of a Liver Stem Cell Line

Nadia Malouf-Anderson

Pathology and Laboratory Medicine
University of North Carolina

Transdifferentiation of adult somatic stem cells holds promise as a means for tissue repair. Yet many aspects, including clonality of stem cells, their function in the host environment, and their lack of fusion with differentiated host cells, warrant further studies. We have used a rat liver stem cell line (WB F344) cloned from a single liver non parenchymal epithelial cell to demonstrate that these adult derived liver stem cells respond to inductive signals from the microenvironment in which they engraft and differentiate into a phenotype that is characteristic of cells in the host microenvironment.

In the heart, in vivo, WB F344 cells differentiate in a niche dependent manner into epicardial and endothelial cells in the epicardium and endocardium, respectively, and into mature myocytes that exhibit anatomical couplings with gap junctions in the myocardium. WB F344 cells acquire a cardiac myocyte phenotype and function when co cultured with neonatal cardiac cells. They exhibit a rhythmic beating, Ca²⁺ transients, and become dye coupled with differentiated host neonatal myocytes.

When injected in the tail vein of nude mice, WB F344 home into the bone marrow where they acquire a hematopoietic progenitor lineage. They form CFU-mix and preB-CFU colonies in clonogenic assays.

Taking advantage of xenogeneic differences between the WB F344 rat cells and the mouse host cells, a mouse L1 DNA element which is repetitive throughout the mouse genome was used to demonstrate that fusion between differentiated host cells and WB F344 derived cardiac or hematopoietic cells did not take place.

Collectively, these studies demonstrate the plasticity of an adult liver stem cell where function, clonality and lack of fusion criteria are met.