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1.
J Pathol ; 262(1): 61-75, 2024 01.
Article in English | MEDLINE | ID: mdl-37796386

ABSTRACT

Pancreatic stellate cells (PSCs) are stromal cells in the pancreas that play an important role in pancreatic pathology. In chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC), PSCs are known to get activated to form myofibroblasts or cancer-associated fibroblasts (CAFs) that promote stromal fibroinflammatory reactions. However, previous studies on PSCs were mainly based on the findings obtained using ex vivo expanded PSCs, with few studies that addressed the significance of in situ tissue-resident PSCs using animal models. Their contributions to fibrotic reactions in CP and PDAC are also lesser-known. These limitations in our understanding of PSC biology have been attributed to the lack of specific molecular markers of PSCs. Herein, we established Meflin (Islr), a glycosylphosphatidylinositol-anchored membrane protein, as a PSC-specific marker in both mouse and human by using human pancreatic tissue samples and Meflin reporter mice. Meflin-positive (Meflin+ ) cells contain lipid droplets and express the conventional PSC marker Desmin in normal mouse pancreas, with some cells also positive for Gli1, the marker of pancreatic tissue-resident fibroblasts. Three-dimensional analysis of the cleared pancreas of Meflin reporter mice showed that Meflin+ PSCs have long and thin cytoplasmic protrusions, and are localised on the abluminal side of vessels in the normal pancreas. Lineage tracing experiments revealed that Meflin+ PSCs constitute one of the origins of fibroblasts and CAFs in CP and PDAC, respectively. In these diseases, Meflin+ PSC-derived fibroblasts showed a distinctive morphology and distribution from Meflin+ PSCs in the normal pancreas. Furthermore, we showed that the genetic depletion of Meflin+ PSCs accelerated fibrosis and attenuated epithelial regeneration and stromal R-spondin 3 expression, thereby implying that Meflin+ PSCs and their lineage cells may support tissue recovery and Wnt/R-spondin signalling after pancreatic injury and PDAC development. Together, these data indicate that Meflin may be a marker specific to tissue-resident PSCs and useful for studying their biology in both health and disease. © 2023 The Pathological Society of Great Britain and Ireland.


Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Pancreatitis, Chronic , Animals , Humans , Mice , Carcinoma, Pancreatic Ductal/pathology , Fibrosis , Pancreas/pathology , Pancreatic Neoplasms/pathology , Pancreatic Stellate Cells/pathology , Pancreatitis, Chronic/genetics , Pancreatitis, Chronic/metabolism , Pancreatitis, Chronic/pathology , Regeneration
2.
Asian J Endosc Surg ; 10(4): 446-449, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28349649

ABSTRACT

A 60-year old woman had been hospitalized in a psychiatric hospital for 40 years for schizophrenia. An X-ray was performed when she fell, which showed needles in the abdominal field. After additional examinations and questioning, the patient was diagnosed with needles in the abdominal cavity, which were assumed to have been ingested and to have perforated the GI tract 40 years ago. They were removed by laparoscopic surgery. The needles were found in the omentum and near the left ovary. There were no inflammatory reactions around them. There have been previous reports about the removal of intra-abdominal foreign bodies, but foreign body reaction occurred in most of the reports. Our case had the longest period from ingestion of the foreign bodies to their removal. Laparoscopy and intraoperative fluoroscopy are useful for removing intra-abdominal foreign bodies because of their ability to help discriminate between structures and to navigate in real time.


Subject(s)
Foreign Bodies/diagnostic imaging , Foreign Bodies/surgery , Gastrointestinal Tract , Laparoscopy , Needles , Female , Foreign Bodies/etiology , Humans , Middle Aged , Time Factors , Tomography, X-Ray Computed
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