scholarly journals Isolation of quiescent pancreatic stellate cells from rat and human pancreas

2011 ◽  
Keyword(s):  
Stellate Cells ◽  
Pancreatic Stellate Cells ◽  
Human Pancreas

Hypoxia activates pancreatic stellate cells: Development of an organotypic culture model of thick slices of normal human pancreas

Pancreatology ◽  
2012 ◽  
Vol 12 (6) ◽  
pp. 588
Author(s):  
V. Rebours ◽  
M. Albuquerque ◽  
P. Ruszniewski ◽  
A. Sauvanet ◽  
V. Paradis ◽  
...  
Keyword(s):  
Organotypic Culture ◽  
Stellate Cells ◽  
Pancreatic Stellate Cells ◽  
Human Pancreas ◽  
Culture Model ◽  
Normal Human

870 Hypoxia Activates Pancreatic Stellate Cells: Development of an Organotypic Culture Model of Thick Slices of Normal Human Pancreas

2012 ◽  
Vol 142 (5) ◽  
pp. S-150
Author(s):  
Vinciane Rebours ◽  
Miguel Albuquerque ◽  
Philippe B. Ruszniewski ◽  
Alain Sauvanet ◽  
Valérie Paradis ◽  
...  
Keyword(s):  
Organotypic Culture ◽  
Stellate Cells ◽  
Pancreatic Stellate Cells ◽  
Human Pancreas ◽  
Culture Model ◽  
Normal Human

NADPH oxidase plays a crucial role in the activation of pancreatic stellate cells

2008 ◽  
Vol 294 (1) ◽  
pp. G99-G108 ◽  
Author(s):  
Atsushi Masamune ◽  
Takashi Watanabe ◽  
Kazuhiro Kikuta ◽  
Kennichi Satoh ◽  
Tooru Shimosegawa
Keyword(s):  
Chronic Pancreatitis ◽  
Nadph Oxidase ◽  
Stellate Cells ◽  
Pancreatic Fibrosis ◽  
Pancreatic Stellate Cells ◽  
Human Pancreas ◽  
Ros Production ◽  
Chemokine Production ◽  
Cell Functions ◽  
Diphenylene Iodonium

Activated pancreatic stellate cells (PSCs) play an important role in pancreatic fibrosis and inflammation, where oxidative stress is implicated in the pathogenesis. NADPH oxidase might be a source of reactive oxygen species (ROS) in the injured pancreas. This study aimed to clarify the expression and regulation of cell functions by NADPH oxidase in PSCs. PSCs were isolated from rat and human pancreas tissues. Expression of NADPH oxidase was assessed by reverse transcription-PCR and immunostaining. Intracellular ROS production was assessed using 2′,7′-dichlorofluorescin diacetate. The effects of diphenylene iodonium (DPI) and apocynin, inhibitors of NADPH oxidase, on key parameters of PSC activation were evaluated in vitro. In vivo, DPI (at 1 mg·kg body wt−1·day−1) was administered in drinking water to 10-wk-old male Wistar Bonn/Kobori rats for 10 wk and to rats with chronic pancreatitis induced by dibutyltin dichloride (DBTC). PSCs expressed key components of NADPH oxidase (p22phox, p47phox, NOX1, gp91phox/NOX2, NOX4, and NOX activator 1). PDGF-BB, IL-1β, and angiotensin II induced ROS production, which was abolished by DPI and apocynin. DPI inhibited PDGF-induced proliferation, IL-1β-induced chemokine production, and expression of α-smooth muscle actin and collagen. DPI inhibited transformation of freshly isolated cells to a myofibroblast-like phenotype. In addition, DPI inhibited the development of pancreatic fibrosis in Wistar Bonn/Kobori rats and in rats with DBTC-induced chronic pancreatitis. In conclusion, PSCs express NADPH oxidase to generate ROS, which mediates key cell functions and activation of PSCs. NADPH oxidase might be a potential target for the treatment of pancreatic fibrosis.

Identification of markers for quiescent pancreatic stellate cells in the normal human pancreas

2017 ◽  
Vol 148 (4) ◽  
pp. 359-380 ◽  
Author(s):  
Michael Friberg Bruun Nielsen ◽  
Michael Bau Mortensen ◽  
Sönke Detlefsen
Keyword(s):  
Stellate Cells ◽  
Pancreatic Stellate Cells ◽  
Human Pancreas ◽  
Normal Human

scholarly journals Activation of Pancreatic Stellate Cells Is Beneficial for Exocrine but Not Endocrine Cell Differentiation in the Developing Human Pancreas

2021 ◽  
Vol 9 ◽  
Author(s):  
Jinming Li ◽  
Bijun Chen ◽  
George F. Fellows ◽  
Cynthia G. Goodyer ◽  
Rennian Wang
Keyword(s):  
Cell Differentiation ◽  
Beta Cell ◽  
Islet Cell ◽  
Stellate Cell ◽  
Stellate Cells ◽  
Pancreatic Tissue ◽  
Pancreatic Stellate Cells ◽  
Small Subset ◽  
Human Pancreas ◽  
Pancreatic Development

Pancreatic stellate cells (PaSCs) are non-endocrine, mesenchymal-like cells that reside within the peri-pancreatic tissue of the rodent and human pancreas. PaSCs regulate extracellular matrix (ECM) turnover in maintaining the integrity of pancreatic tissue architecture. Although there is evidence indicating that PaSCs are involved in islet cell survival and function, its role in islet cell differentiation during human pancreatic development remains unclear. The present study examines the expression pattern and functional role of PaSCs in islet cell differentiation of the developing human pancreas from late 1st to 2nd trimester of pregnancy. The presence of PaSCs in human pancreata (8–22 weeks of fetal age) was characterized by ultrastructural, immunohistological, quantitative RT-PCR and western blotting approaches. Using human fetal PaSCs derived from pancreata at 14–16 weeks, freshly isolated human fetal islet-epithelial cell clusters (hIECCs) were co-cultured with active or inactive PaSCs in vitro. Ultrastructural and immunofluorescence analysis demonstrated a population of PaSCs near ducts and newly formed islets that appeared to make complex cell-cell dendritic-like contacts. A small subset of PaSCs co-localized with pancreatic progenitor-associated transcription factors (PDX1, SOX9, and NKX6-1). PaSCs were highly proliferative, with significantly higher mRNA and protein levels of PaSC markers (desmin, αSMA) during the 1st trimester of pregnancy compared to the 2nd trimester. Isolated human fetal PaSCs were identified by expression of stellate cell markers and ECM. Suppression of PaSC activation, using all-trans retinoic acid (ATRA), resulted in reduced PaSC proliferation and ECM proteins. Co-culture of hIECCs, directly on PaSCs or indirectly using Millicell® Inserts or using PaSC-conditioned medium, resulted in a reduction the number of insulin+ cells but a significant increase in the number of amylase+ cells. Suppression of PaSC activation or Notch activity during the co-culture resulted in an increase in beta-cell differentiation. This study determined that PaSCs, abundant during the 1st trimester of pancreatic development but decreased in the 2nd trimester, are located near ductal and islet structures. Direct and indirect co-cultures of hIECCs with PaSCs suggest that activation of PaSCs has opposing effects on beta-cell and exocrine cell differentiation during human fetal pancreas development, and that these effects may be dependent on Notch signaling.

scholarly journals Hypoxia Pathways and Cellular Stress Activate Pancreatic Stellate Cells: Development of an Organotypic Culture Model of Thick Slices of Normal Human Pancreas

PLoS ONE ◽  
2013 ◽  
Vol 8 (9) ◽  
pp. e76229 ◽  
Author(s):  
Vinciane Rebours ◽  
Miguel Albuquerque ◽  
Alain Sauvanet ◽  
Philippe Ruszniewski ◽  
Philippe Lévy ◽  
...  
Keyword(s):  
Organotypic Culture ◽  
Cellular Stress ◽  
Stellate Cells ◽  
Pancreatic Stellate Cells ◽  
Human Pancreas ◽  
Culture Model ◽  
Normal Human

scholarly journals Immune Cell Modulation of the Extracellular Matrix Contributes to the Pathogenesis of Pancreatic Cancer

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 901
Author(s):  
Ramiz S. Ahmad ◽  
Timothy D. Eubank ◽  
Slawomir Lukomski ◽  
Brian A. Boone
Keyword(s):  
Pancreatic Cancer ◽  
Extracellular Matrix ◽  
Immune Cells ◽  
Immune Cell ◽  
Treatment Strategies ◽  
Stellate Cells ◽  
Pancreatic Stellate Cells ◽  
Ductal Adenocarcinoma ◽  
Cellular Mechanisms ◽  
Novel Treatment Strategies

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with a five-year survival rate of only 9%. PDAC is characterized by a dense, fibrotic stroma composed of extracellular matrix (ECM) proteins. This desmoplastic stroma is a hallmark of PDAC, representing a significant physical barrier that is immunosuppressive and obstructs penetration of cytotoxic chemotherapy agents into the tumor microenvironment (TME). Additionally, dense ECM promotes hypoxia, making tumor cells refractive to radiation therapy and alters their metabolism, thereby supporting proliferation and survival. In this review, we outline the significant contribution of fibrosis to the pathogenesis of pancreatic cancer, with a focus on the cross talk between immune cells and pancreatic stellate cells that contribute to ECM deposition. We emphasize the cellular mechanisms by which neutrophils and macrophages, specifically, modulate the ECM in favor of PDAC-progression. Furthermore, we investigate how activated stellate cells and ECM influence immune cells and promote immunosuppression in PDAC. Finally, we summarize therapeutic strategies that target the stroma and hinder immune cell promotion of fibrogenesis, which have unfortunately led to mixed results. An enhanced understanding of the complex interactions between the pancreatic tumor ECM and immune cells may uncover novel treatment strategies that are desperately needed for this devastating disease.

scholarly journals ITGA5 inhibition in pancreatic stellate cells attenuates desmoplasia and potentiates efficacy of chemotherapy in pancreatic cancer

2019 ◽  
Vol 5 (9) ◽  
pp. eaax2770 ◽  
Author(s):  
Praneeth R. Kuninty ◽  
Ruchi Bansal ◽  
Susanna W. L. De Geus ◽  
Deby F. Mardhian ◽  
Jonas Schnittert ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Tumor Stroma ◽  
Stellate Cells ◽  
Pancreatic Stellate Cells ◽  
Ductal Adenocarcinoma ◽  
Tumor Penetration ◽  
Desmoplastic Stroma ◽  
Integrin Α5

Abundant desmoplastic stroma is the hallmark for pancreatic ductal adenocarcinoma (PDAC), which not only aggravates the tumor growth but also prevents tumor penetration of chemotherapy, leading to treatment failure. There is an unmet clinical need to develop therapeutic solutions to the tumor penetration problem. In this study, we investigated the therapeutic potential of integrin α5 (ITGA5) receptor in the PDAC stroma. ITGA5 was overexpressed in the tumor stroma from PDAC patient samples, and overexpression was inversely correlated with overall survival. In vitro, knockdown of ITGA5 inhibited differentiation of human pancreatic stellate cells (hPSCs) and reduced desmoplasia in vivo. Our novel peptidomimetic AV3 against ITGA5 inhibited hPSC activation and enhanced the antitumor effect of gemcitabine in a 3D heterospheroid model. In vivo, AV3 showed a strong reduction of desmoplasia, leading to decompression of blood vasculature, enhanced tumor perfusion, and thereby the efficacy of gemcitabine in co-injection and patient-derived xenograft tumor models.

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