Signals from pancreatic mesoderm influence the expression of a pancreatic phenotype in hepatic stem-like cell line PHeSC-A2 in vitro: A preliminary study

The ex vivo generation of pancreatic cells from adult hepatic stem cells for subsequent transplantation has been proposed as a novel treatment for Diabetes mellitus. The pancreas and liver, closely related developmentally, may retain a shared (hepatopancreatic) stem cell whose plasticity could be exploited to differentiate into either lineage, dependent on environmental signals. This novel study investigated whether signals from pancreatic mesoderm could induce the differentiation of adult hepatic stem cell-like cells into pancreatic endocrine cells in vitro. A porcine hepatic stem-like cell line, designated PHeSC-A2, was co-cultured with quail pancreatic mesoderm in a Growth Factor Reduced Matrigel-Ham's F12.ITS culture system. Immunocytochemical studies revealed insulin- and glucagon-producing cells. Assessment of nuclear morphology indicated that these endocrine cells were PHeSC-A2-derived. It is thus proposed that the PHeSC-A2 cell line has a higher level of plasticity than previously indicated. These preliminary results and assessment of published data have led to the following postulations: (a) permissive signaling from pancreatic mesoderm suffices to induce hepatic stem cells to assume a pancreatic lineage, (b) the pancreatic phenotype assumed by hepatic stem cells is a default state, (c) the differentiation capacity embodied by these cells indicates the existence of a hepatopancreatic stem cell lineage.