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2016 ; 228
(3
): 474-86
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Progenitor cell niches in the human pancreatic duct system and associated
pancreatic duct glands: an anatomical and immunophenotyping study
#MMPMID26610370
Carpino G
; Renzi A
; Cardinale V
; Franchitto A
; Onori P
; Overi D
; Rossi M
; Berloco PB
; Alvaro D
; Reid LM
; Gaudio E
J Anat
2016[Mar]; 228
(3
): 474-86
PMID26610370
show ga
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 ?m) 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.