Fibrosis Of Pancreatic Tissue Research Articles

NOD alleles at Idd1 and Idd2 loci drive exocrine pancreatic inflammation.

Non-obese diabetic (NOD) mice spontaneously develop autoimmune diabetes and have enabled the identification of several loci associated with diabetes susceptibility, termed insulin-dependent diabetes (Idd). The generation of congenic mice has allowed the characterization of the impact of several loci on disease susceptibility. For instance, NOD.B6-Idd1 and B6.NOD-Idd1 congenic mice were instrumental in demonstrating that susceptibility alleles at the MHC locus (known as Idd1) are necessary but not sufficient for autoimmune diabetes progression. We previously showed that diabetes resistance alleles at the Idd2 locus provide significant protection from autoimmune diabetes onset, second to Idd1. In search of the minimal genetic factors required for T1D onset, we generated B6.Idd1.Idd2 double-congenic mice. Although the combination of Idd1 and Idd2 is not sufficient to induce diabetes onset, we observed immune infiltration in the exocrine pancreas of B6.Idd2 mice, as well as an increase in neutrophils and pancreatic tissue fibrosis. In addition, we observed phenotypic differences in T-cell subsets from B6.Idd1.Idd2 mice relative to single-congenic mice, suggesting epistatic interaction between Idd1 and Idd2 in modulating T-cell function. Altogether, these data show that Idd1 and Idd2 susceptibility alleles are not sufficient for autoimmune diabetes but contribute to inflammation and immune infiltration in the pancreas.

Combinational Treatment Involving Decellularized Extracellular Matrix Hydrogels With Mesenchymal Stem Cells Increased the Efficacy of Cell Therapy in Pancreatitis

Cell transplantation using mesenchymal stem cells (MSCs) has emerged as a promising approach to repairing and regenerating injured or impaired organs. However, the survival and retention of MSCs following transplantation remain a challenge. Therefore, we investigated the efficacy of co-transplantation of MSCs and decellularized extracellular matrix (dECM) hydrogels, which have high cytocompatibility and biocompatibility. The dECM solution was prepared by enzymatic digestion of an acellular porcine liver scaffold. It could be gelled and formed into porous fibrillar microstructures at physiological temperatures. MSCs expanded three-dimensionally in the hydrogel without cell death. Compared to the 2-dimensional cell culture, MSCs cultured in the hydrogel showed increased secretion of hepatocyte growth factor (HGF) and tumor necrosis factor-inducible gene 6 protein (TSG-6), both of which are major anti-inflammatory and anti-fibrotic paracrine factors of MSCs, under TNFα stimulation. In vivo experiments showed that the co-transplantation of MSCs with dECM hydrogel improved the survival rate of engrafted cells compared to those administered without the hydrogel. MSCs also demonstrated therapeutic effects in improving inflammation and fibrosis of pancreatic tissue in a dibutyltin dichloride (DBTC)-induced rat pancreatitis model. Combinational use of dECM hydrogel with MSCs is a new strategy to overcome the challenges of cell therapy using MSCs and can be used for treating chronic inflammatory diseases in clinical settings.

Application of endoscopic retrograde cholangiopancreatology in pediatric chronic pancreatitis

Chronic pancreatitis is a focal or diffuse chronic inflammation and fibrosis of pancreatic tissue, which is progressive, persistent and irreversible.Chronic pancreatitis in children has its own characteristics of early onset and frequent occurrence, which greatly affects the nutritional status and quality of life of children.Recently, diagnosis and treatment of this severe inflammation gradually improved with a burgeoning technique: endoscopic retrograde cholangiopancreatography (ERCP), especially in the treatment of pediatric chronic pancreatitis.The detection rate of the disease has been increasing year by year.As an effective and safe procedure for the treatment of chronic pancreatitis in children, ERCP has replaced traditional surgery and become the first-line treatment method for pediatric chronic pancreatitis. Key words: Child; Chronic pancreatitis; Endoscopic retrograde cholangiopancreatogy

Assessment of Pancreatic Hardness—Surgeon versus Durometer

This study reports the first results of durometrically measured hardness of human pancreas and investigates its correlation to palpatory determined hardness, grade of pancreatic fibrosis, and preoperatively determined radiodensity. Fifty-two patients with pancreatic resections were prospectively recruited. Hardness of samples from pancreatic cancer, chronic pancreatitis, and normal pancreas was measured using a durometer on a 0-100 Shore units (SU) scale. Three pancreatic surgeons palpated the pancreas and reported their assessment of hardness on a subjective 0-100 "Bochum units" (BU) scale. Radiodensity and fibrosis of pancreatic tissue were used for comparison. Pancreatic hardness differed significantly in normal pancreas, chronic pancreatitis, and pancreatic cancer; 30 SU, 51 SU, and 65.8 SU, respectively. Palpatory hardness of normal pancreas was 20 BU and of pancreatitis 60 BU. It correlated well to durometric readings: r(2)=0.56, P<0.00001. Fibrosis grade and radiodensity correlated neither to durometry nor to palpation. Pancreatic leak developed 4/20 (20%) patients with normal pancreas vs. 1/32 (3.1%) with chronic pancreatitis in the resection margin, P<0.05. Palpatory assessment of pancreatic hardness performed by experienced surgeons correlated well to durometric measurements and remains the method of choice for intraoperative decision making. Durometry was more precise and should be considered in studies on pancreatic texture and for teaching purposes. Hardness and fibrosis grade appeared to be independent characteristics of pancreatic texture.