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IVIM MRI of the Pancreas
Published in Denis Le Bihan, Mami Iima, Christian Federau, Eric E. Sigmund, Intravoxel Incoherent Motion (IVIM) MRI, 2018
Miriam Klauß, Philipp Mayer, Bram Stieltjes
In many studies fibrosis was accompanied by pancreatic steatosis: the fat fraction was significantly higher in patients with advanced fibrosis (F2–F3) than in patients with mild or no fibrosis (F0–F1) [34]. It is plausible that the increased extracellular matrix via pancreatic stellate cell activation and fat accumulation in the pancreatic fibrosis may disturb pancreatic perfusion. But it remains unclear why ADCtot and D in this study did not show significant differences between F0–F1 and F2–F3. The inconsistency between ADCtot, D, and pancreatic fibrosis has been reported previously [26]. However, Yoon et al. assume that fat accumulation in patients with no fibrosis as well as that in patients with advanced fibrosis could contribute to diffusion restriction and may counteract the ADCtot or D values as a confounder.
Pancreatic disease
Published in Nizar Zein, Bret Lashner, The Year in Gastroenterology and Hepatology, 2005
B A C K R o u N D Chronic alcoholism is a major health problem worldwide and is the G most common cause of acute and chronic pancreatitis in industrialized countries, including the USA. Despite the overwhelming epidemiological link between excessive alcohol intake and pancreatitis, the mechanism(s) of ethanol-induced injury t o the pancreas are not fully understood. Several potential mechanisms of ethanol-induced injury have been proposed, including the role of stellate cell activation in pancreatic fibrosis. In the following section, we discuss two review articles published in 2003 outlining the current understanding of the pathophysiology of alcohol-induced pancreatic injury. These two reviews, although not original research studies, may set the tone and outline the future research focus in the field of alcoholic pancreatitis. The review by Apte et a/. specifically focuses on the role of pancreatic stellate cells in pancreatic fibrosis.
Liver, Gallbladder, and Exocrine Pancreas
Published in Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard, Toxicologic Pathology, 2018
Russell C. Cattley, James A. Popp, Steven L. Vonderfecht
Although the exocrine pancreas contains the expected vascular, neural, and connective tissue support structures, these features will not be discussed further. However, an additional cell type, the pancreatic stellate cell, deserves additional mention since it has attracted attention as an important element in the reparative response to exocrine pancreatic injury and in pancreatic cancer. Pancreatic stellate cells are myofibroblast-like cells that are present in the periacinar space of the exocrine pancreas and have long cytoplasmic processes that encircle the base of the acinus. The cells are also found in the periductal and perivascular regions of the pancreas (Omary et al. 2007). They are similar to hepatic stellate cells and, in the quiescent state, are characterized by the presence of the intermediate filament proteins, desmin and glial fibrillary acidic protein (GFAP), and intracellular, vitamin A-containing fat droplets. These features together distinguish pancreatic stellate cells from normal fibroblasts (Apte et al. 1998; Bachem et al. 1998). In the normal state, pancreatic stellate cells may maintain normal turnover of extracellular matrix by regulating production and degradation of matrix proteins. The cells also express Toll-like receptors, suggesting a role in innate immunity (Apte et al. 2015). Pancreatic stellate cells are activated by a variety of factors such as cytokines, growth factors, and angiotensin II, and when activated, lose their fat droplets and express α-smooth muscle actin (α-SMA) and extracellular matrix proteins such as collagen types I and III and fibronectin as well as matrix-degrading enzymes such as those in the metalloproteinase family. Given the expression of such a diversity of proteins and the ability to respond to a variety of “inflammatory” mediators, it is not surprising that pancreatic stellate cells are thought to have a key role in the fibrosis that accompanies chronic pancreatitis and pancreatic adenocarcinoma (Masamune and Shimosegawa 2013; Omary et al. 2007). The role of stellate cells in pancreatic cancer is the subject of active investigation with apparently conflicting results suggesting their role is perhaps dependent on time, context, and model (Apte et al. 1998; Apte et al. 2013; Vonlaufen et al. 2008; Özdemir et al. 2014). In this regard, the possibility that subpopulations of stellate cells differentially promote growth of pancreatic cancer certainly adds to this complexity (Ikenaga et al. 2010).
HSP47: a potential target for fibrotic diseases and implications for therapy
Published in Expert Opinion on Therapeutic Targets, 2021
Pierre-Simon Bellaye, Olivier Burgy, Philippe Bonniaud, Martin Kolb
Specific delivery of HSP47 siRNA to hepatic stellate cells (HSC), key collagen producers in hepatic fibrosis, has been achieved by systemic administration of vitamin A-coupled liposomes. This strategy exploits the fact that HSC are crucial for both fibrogenesis and uptake of vitamin A and coupling liposomes containing anti-HSP47 siRNA with vitamin A facilitates the specific targeting of HSCs [76], resulting even in resolution of liver fibrosis [77]. Pancreatic stellate cells display similar characteristics as HSC such as collagen synthesis, vitamin A storage, and expression of HSP47. Ishiwatari et al. demonstrated that HSP47 siRNA in vitamin A-coupled liposomes were specifically distributed in fibrotic areas in rats with pancreatic fibrosis with a specific uptake in pancreatic stellate cells [78]. Very recently, this approach has been successful in fibrotic disorders affecting other organs including lung, eyes and skin (Figure 2 [79–81],) which highlights that vitamin A storage is increased in myofibroblasts independently of the affected organ. As a consequence, HSP47 siRNA delivery through vitamin A liposomes could potentially be a universal approach to target fibrosis across organs.
Pathophysiological and immunohistochemical analysis of pancreas after renal ischemia/reperfusion injury: protective role of melatonin*
Published in Archives of Physiology and Biochemistry, 2020
Sahar M. El Agaty, Asmaa Ibrahim Ahmed
Another fundamental observation in the current study is the mild intralobular collagen deposition observed by examination of Masson’s trichrome-stained sections of I/R group. Pancreatic stellate cells (PSCs) are involved in the pathogenesis of pancreatic fibrosis. In normal pancreas, PSCs with retinoid-storing phenotype are present in small number in periacinar regions. After stimulation by pancreatic injury secondary to I/R, PSCs change their phenotype to highly active myofibroblast-like cells and produce majority of extracellular matrix, including collagen type I, III and IV, fibronectin and proteoglycan matrix (Tanioka et al.2006, Warzecha et al.2004) . Additionally, I/R was found to increase fibroblast-like growth factor-2 content in pancreatic acinar cells between the 12th and 24th h. and between the 5th and 9th day of reperfusion (Chen et al.2010). Previous studies have reported that excessive production of free radicals enhances collagen deposition in the pancreas (Sudhakara et al.2018) and promotes fibrosis by direct activation of PSCs (Chen et al.2010). Therefore, the oxidative stress induced by renal I/R, herein, might activate the fibrotic process.
B lymphocytes contribute to stromal reaction in pancreatic ductal adenocarcinoma
Published in OncoImmunology, 2020
Claudia Minici, Elena Rigamonti, Marco Lanzillotta, Antonella Monno, Lucrezia Rovati, Takashi Maehara, Naoki Kaneko, Vikram Deshpande, Maria Pia Protti, Lucia De Monte, Cristina Scielzo, Stefano Crippa, Paolo Giorgio Arcidiacono, Erica Dugnani, Lorenzo Piemonti, Massimo Falconi, Shiv Pillai, Angelo A. Manfredi, Emanuel Della-Torre
In apparent contrast with this aggressiveness, the majority of the tumor volume in PDAC is not made of malignant cells, but of a desmoplastic reaction consisting of cancer-associated fibroblasts (CAF) and immune cells .2,3 Pancreatic CAF are believed to originate from different cellular sources, including pancreatic stellate cells, mesenchymal stem cells (MSC) resident fibroblasts, and epithelial cells .4,5 Although CAF have been classically associated with tumor growth, immune suppression, and metastatic dissemination, recent evidences have challenged these tumor-promoting properties and showed more aggressive PDAC behavior in CAF deprived mouse models.2–8 These findings suggest a complex network of signals between PDAC and CAF that is not uniformly stimulatory or inhibitory, and possibly support the existence of different tumor-promoting and tumor-suppressing populations of CAF. Indeed, a previously unappreciated heterogeneity in PDAC fibroblasts has been recently observed, with tumor-promoting subsets of CAF expressing variable combinations of activation and mesenchymal stem cell markers such as the secreted protein acidic and rich in cysteine (SPARC), the encoding fibroblast activation protein (FAP), COL1A1, COL1A2, and COL3A1 collagen genes, CD73, and CD90.9,10 In the rapidly evolving field of PDAC, understanding of the molecular mechanisms driving CAF differentiation and activation could lead to the identification of novel mechanistic insights as well as to innovative therapeutic targets.