Innervation of the proximal human biliary tree

Area of Science:

• Hepatology
• Neuroscience
• Cell Biology

Background:

• The autonomic nervous system influences liver functions like bile secretion and progenitor cell activity.
• The precise anatomical connections between nerves and the proximal biliary tree, including the canals of Hering stem cell niche, remain unclear.

Purpose of the Study:

• To investigate the anatomical relationship between nerves and the proximal biliary tree, focusing on the canals of Hering.
• To determine the nature and extent of biliary innervation in the normal adult liver.

Main Methods:

• Utilized double immunostaining (fluorescence, histochemistry) for cholangiocytes, nerves (S100, neurofilament protein, PGP9.5, tyrosine hydroxylase), and stellate cells (CRBP-1).
• Examined liver sections from autopsies and surgical resections.
• Employed electron microscopy to confirm nerve proximity to ductules.

Main Results:

• Extensive nerve contact observed with interlobular bile ducts, bile ductules, and canals of Hering.
• Biliary-nerve contacts were more frequent in interlobular bile ducts (57%) than in ductules and canals of Hering (33%).
• Nerves, predominantly adrenergic (tyrosine hydroxylase-positive), were found adjacent to the biliary basement membrane, with some direct contact with cholangiocytes.

Conclusions:

• Novel findings reveal extensive biliary innervation, including the stem/progenitor cell niche.
• Direct cholangiocyte-nerve interactions may mediate biliary innervation.
• These findings have significant implications for understanding neuromodulation of biliary physiology and hepatic stem/progenitor cell function.