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Updated: May 9, 2026

In Vitro Colony Assays for Characterizing Tri-potent Progenitor Cells Isolated from the Adult Murine Pancreas
Published on: June 10, 2016
Biliary tree stem cells, precursors to pancreatic committed progenitors: evidence for possible life-long pancreatic
Yunfang Wang1, Giacomo Lanzoni, Guido Carpino
1Department of Cell Biology and Physiology, Program in Molecular Biology and Biotechnology, Lineberger Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
Insights
Bile duct stem cells can differentiate into pancreatic cells, forming functional neoislets. These engineered pancreatic tissues can treat diabetes by regulating blood glucose levels in mice.
Area of Science:
- Stem cell biology
- Developmental biology
- Endocrinology
Background:
- Peribiliary glands (PBGs) and pancreatic duct glands (PDGs) form a continuous cell network.
- These glands contain cells with overlapping maturational lineages, suggesting a developmental link.
Purpose of the Study:
- To investigate the maturational lineages and stem cell potential of PBGs and PDGs.
- To explore the possibility of generating functional pancreatic tissue from these cells for therapeutic applications.
Main Methods:
- Analysis of cell markers for pluripotency, proliferation, and differentiation in PBGs and PDGs.
- In vitro culture of biliary tree-derived and pancreas-derived cells.
- Differentiation of cells into neoislets using specific culture conditions.
- Implantation of neoislets into diabetic mice to assess efficacy.
Main Results:
- Biliary tree-derived cells exhibit stem cell characteristics and act as precursors to pancreatic progenitors.
- Engineered neoislets derived from these cells possess ultrastructural and functional characteristics of natural islets.
- Implanted neoislets secreted human C-peptide, regulated glucose, and alleviated hyperglycemia in diabetic mice.
Conclusions:
- Biliary tree-derived stem cells and their progenitor connections offer a framework for pancreatic organogenesis.
- These findings open avenues for regenerative medicine strategies in treating diabetes.
Abstract:
Peribiliary glands (PBGs) in bile duct walls, and pancreatic duct glands (PDGs) associated with pancreatic ducts, in humans of all ages, contain a continuous, ramifying network of cells in overlapping maturational lineages. We show that proximal (PBGs)-to-distal (PDGs) maturational lineages start near the duodenum with cells expressing markers of pluripotency (NANOG, OCT4, and SOX2), proliferation (Ki67), self-replication (SALL4), and early hepato-pancreatic commitment (SOX9, SOX17, PDX1, and LGR5), transitioning to PDG cells with no expression of pluripotency or self-replication markers, maintenance of pancreatic genes (PDX1), and expression of markers of pancreatic endocrine maturation (NGN3, MUC6, and insulin). Radial-axis lineages start in PBGs near the ducts' fibromuscular layers with stem cells and end at the ducts' lumens with cells devoid of stem cell traits and positive for pancreatic endocrine genes. Biliary tree-derived cells behaved as stem cells in culture under expansion conditions, culture plastic and serum-free Kubota's Medium, proliferating for months as undifferentiated cells, whereas pancreas-derived cells underwent only approximately 8-10 divisions, then partially differentiated towards an islet fate. Biliary tree-derived cells proved precursors of pancreas' committed progenitors. Both could be driven by three-dimensional conditions, islet-derived matrix components and a serum-free, hormonally defined medium for an islet fate (HDM-P), to form spheroids with ultrastructural, electrophysiological and functional characteristics of neoislets, including glucose regulatability. Implantation of these neoislets into epididymal fat pads of immunocompromised mice, chemically rendered diabetic, resulted in secretion of human C-peptide, regulatable by glucose, and able to alleviate hyperglycemia in hosts. The biliary tree-derived stem cells and their connections to pancreatic committed progenitors constitute a biological framework for life-long pancreatic organogenesis.
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