Abstract
Determined stem cells for liver and pancreas are present in stem cell niches, peribiliary glands (PBGs), throughout the biliary tree. PBGs are connected to intrahepatic stem cell niches, canals of Hering, and niches of committed progenitors, pancreatic duct glands. The phenotypic traits in the most primitive populations comprise both liver and pancreatic markers (transcription factors, pluripotency genes, endodermal genes), and their highest numbers are in large intrahepatic bile ducts and the hepato-pancreatic common duct. Their descendants have phenotypic traits implicating maturational lineages along a radial axis within bile duct walls and a proximal-to-distal axis from duodenum to mature cells near or in the liver or pancreas. The stem cells and lineages constitute a biological framework for hepatic and pancreatic organogenesis throughout life.
Immune- or culture-selected stem cells differentiate to mature cells when transplanted in vivo. In vitro they self-replicate vs. lineage restrict to an adult fate with wholly defined culture conditions.
Clinical trials are ongoing with stem cells transplanted via the hepatic artery into the liver of patients with various diseases and without immunosuppression. The transplants result in significant improvements in liver functions and longer life spans for patients. These findings offer hope for utilizing these stem cell populations for regenerative medicine for liver and pancreas.