Activation of pancreatic stellate cells in human and experimental pancreatic fibrosis

The mechanisms of pancreatic fibrosis are poorly understood. In the liver, stellate cells play an important role in fibrogenesis, Similar cells have recently been isolated from the pancreas and are termed pan creatic stellate cells. The aim of this study was to determine whether pancreatic stellate cell activation occurs during experimental and human pancreatic fibrosis. Pancreatic fibrosis was induced in rats (n = 24) by infusion of trinitrobenzene sulfonic acid (TNBS) into the pancreatic duct. Surgical specimens were obtained from patients with chronic pancreatitis (n = 6). Pancreatic fibrosis was assessed using the Sirius Red stain and immunohistochemistry for collagen type I. Pancreatic stellate cell activation was assessed by staining for alpha-smooth muscle actin (alpha SMA), desmin, and platelet-derived growth factor receptor type beta (PDGFR beta). The relationship of fibrosis to stellate cell activation was studied by staining of serial sections for alpha SMA, desmin, PDGFR beta, and collagen, and by dual-staining for alpha SMA plus either Sirius Red or in situ hybridization for procollagen alpha(1) (I) mRNA. The cellular source of TGF beta was examined by immunohistochemistry, The histological appearances in the TNBS model resembled those found in human chronic pancreatitis. Areas of pancreatic fibrosis stained positively for Sirius Red and collagen type I. Sirius Red staining was associated with alpha SMA-positive cells. alpha SMA staining colocallzed with procollagen alpha(1) (I) mRNA expression. In the rat model, desmin staining was associated with PDGFR beta in areas of fibrosis. TGF beta was maximal in acinar cells adjacent to areas of fibrosis and spindle cells within fibrotic bands. Pancreatic stellate cell activation is associated with fibrosis in both human pancreas and in an animal model. These cells appear to play an important role in pancreatic fibrogenesis.