title: Progenitor cell niches in the human pancreatic duct system and associated pancreatic duct glands: an anatomical and immunophenotyping study.
abstract: Pancreatic duct glands (PDGs) are tubule-alveolar glands associated with the pancreatic duct system and can be considered the anatomical counterpart of peribiliary glands (PBGs) found within the biliary tree. Recently, we demonstrated that endodermal precursor niches exist fetally and postnatally and are composed functionally of stem cells and progenitors within PBGs and of committed progenitors within PDGs. Here we have characterized more extensively the anatomy of human PDGs as novel niches containing cells with multiple phenotypes of committed progenitors. Human pancreata (n = 15) were obtained from cadaveric adult donors. Specimens were processed for histology, immunohistochemistry and immunofluorescence. PDGs were found in the walls of larger pancreatic ducts (diameters > 300 μm) and constituted nearly 4% of the duct wall area. All of the cells identified were negative for nuclear expression of Oct4, a pluripotency gene, and so are presumably committed progenitors and not stem cells. In the main pancreatic duct and in large interlobular ducts, Sox9(+) cells represented 5-30% of the cells within PDGs and were located primarily at the bottom of PDGs, whereas rare and scattered Sox9(+) cells were present within the surface epithelium. The expression of PCNA, a marker of cell proliferation, paralleled the distribution of Sox9 expression. Sox9(+) PDG cells proved to be Pdx1(+) /Ngn3(+/-) /Oct4A(-) . Nearly 10% of PDG cells were positive for insulin or glucagon. Intercalated ducts contained Sox9(+) /Pdx1(+) /Ngn3(+) cells, a phenotype that is presumptive of committed endocrine progenitors. Some intercalated ducts appeared in continuity with clusters of insulin-positive cells organized in small pancreatic islet-like structures. In summary, PDGs represent niches of a population of Sox9(+) cells exhibiting a pattern of phenotypic traits implicating a radial axis of maturation from the bottoms of the PDGs to the surface of pancreatic ducts. Our results complete the anatomical background that links biliary and pancreatic tracts and could have important implications for the common patho-physiology of biliary tract and pancreas.
authors.affiliation: Division of Health Sciences, Department of Movement, Human and Health Sciences, University of Rome 'Foro Italico', Rome, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Carpino
authors.affiliation: Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Renzi
authors.affiliation: Department of Medico-Surgical Sciences and Biotechnologies, Polo Pontino, Sapienza University of Rome, Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cardinale
authors.affiliation: Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Franchitto
authors.affiliation: Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Onori
authors.affiliation: Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy.
authors.forename: Diletta
authors.initials: D
authors.lastname: Overi
authors.affiliation: Department of General Surgery and Organ Transplantation, Sapienza University of Rome, Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Rossi
authors.affiliation: Department of General Surgery and Organ Transplantation, Sapienza University of Rome, Rome, Italy.
authors.forename: Pasquale Bartolomeo
authors.initials: PB
authors.lastname: Berloco
authors.affiliation: Department of Medico-Surgical Sciences and Biotechnologies, Polo Pontino, Sapienza University of Rome, Rome, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Alvaro
authors.affiliation: Department of Cell Biology and Physiology, Program in Molecular Biology and Biotechnology, Lineberger Comprehensive Cancer Center, UNC School of Medicine, Chapel Hill, NC, USA.
authors.forename: Lola M
authors.initials: LM
authors.lastname: Reid
authors.affiliation: Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Gaudio
mesh_terms: D000328:Adult; D053687:Adult Stem Cells / Q000166:cytology*; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010183:Pancreatic Ducts / Q000166:cytology*; D055153:Stem Cell Niche
chemical_list: D015415:Biomarkers
keywords: biliary tract; insulin; pancreas; pancreatic progenitors; stem cell