Differentiation of acinar cells into acinoductular cells in regenerating rat pancreas.
OBJECTIVE
Several lines of experimental data suggest that acinar cells have the potential to differentiate into ductular-like cells, and these newly formed acinoductular cells may act as (facultative) stem cells. The purpose of this study was to test this hypothesis in a model of pancreatic regeneration in rats.


METHODS
In the current study, using a 90% pancreatectomy as a rat model for pancreatic regeneration, we serially examined the pancreatic tissues in a time-dependent manner by conventional histology and immunostaining. Cell proliferation was assessed by in vivo bromodeoxyuridine (BrdU) labeling.


RESULTS
By 24 h after surgery, acini showed depleted granules with more dilated lumens (acinar ectasia). By day 2, focal regions of regeneration appeared which were separated by fibrosis and composed of ductular-like cells (tubular complexes) and acinar cells with dilated lumina. Double immunofluorescent staining revealed that both amylase and CK19 were positive in the same cells localized to the focus of regeneration from the animals on day 2, the phenotype of cells from those regions apparently reverted to acinar cells, and the regions completely disappeared by day 7. By 48 h after surgery, the number of BrdU-positive cells increased 4.3-fold in ductular cells, and 2.5-fold in acinar cells compared with control tissue.


CONCLUSIONS
Acinar cells through acinoductular metaplasia may be a source of pancreatic regeneration.
Tokoro
Takamasa
T
Department of Surgery II, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. tokoro@bk9.so-net.ne.jp
Tezel
Ekmel
E
Nagasaka
Tetsuro
T
Kaneko
Tetsuya
T
Nakao
Akimasa
A
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division; D019084:Fluorescent Antibody Technique, Indirect; D007124:Immunoenzyme Techniques; D008297:Male; D023421:Models, Animal; D010179:Pancreas / Q000166:cytology* / Q000502:physiology* / Q000601:surgery; D010180:Pancreatectomy; D010183:Pancreatic Ducts / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000502:physiology*
D015415:Biomarkers; D001973:Bromodeoxyuridine