precede PaSC activation. Activated PaSCs are located in areas of major necrosis and inflammation that harbour cytokines, growth factors and reactive oxygen species. Inflammatory processes are essential in contributing towards the activation of stellate cells. Therefore, both autocrine and paracrine mediators are involved pancreatic stellate cell activation. Copious amounts of α- SMA-expressing cells are present in fibrotic areas of pancreatic tissue sections in patients with chronic pancreatitis. α-SMA-expressing cells in fibrotic areas yield MRNA encoding pro-collagen α1I, indicating that activated PaSCs are the predominant source of collagen in pancreatic fibrosis. Activated PaSCs and other myo-fibroblast cells contribute to the formation of a provisional matrix at the injury site, which enables cell proliferation, migration and the assembly of new parenchymal cells. In the majority of cases, activated PaSCs recede after the termination of the injurious agent, however repeated pancreatic damage can result in proliferation of PaSCs and eventual fibrosis. In humans, persistent injury to the pancreas is linked with chronic alcohol use, pancreatic duct obstruction and genetic. Chronic damage leads to the sustained activation of the active PaSC phenotype. Diminished production of MMPs by PaSCs also contributes to the fibrotic phenotype. Other factors may also drive the persistent activated state of PaSCs in the event of pancreatitis. For example, PaSCs express protease activated receptor-2 (PAR-2), which is cleaved by trypsin to become active. Active PAR-2 then instigates PaSC growth and collagen synthesis. Cancer Pancreatic adenocarcinomas are recognised by tumour desmoplasia, distinguished by an increase in the connective tissue that surrounds the neoplasm. Activated PaSCs in the tumour desmoplasia of human pancreatic cancers express α-SMA and co-localise with MRNA encoding pro-collagen α1I. These factors are significant contributors of the ECM proteins that compose the desmoplasia. A symbiotic relationship exists between pancreatic adenocarcinoma cells and PaSCs, which leads to an overall increase in the rate of growth of the tumour. For example, culture supernatants from human pancreatic tumour cell lines induce PaSC proliferation and the production of ECM proteins. Pancreatic tumour cells stimulate the proliferation of PaSCs through the secretion of PDGF, and induce PaSC production of ECM proteins by secreting TGF-β1 and FGF-2. Pancreatic tumour cells and PaSCs operate in a symbiotic relationship in animal studies, however data from human pancreatic tumours is limited. Connective tissue growth factor is involved in the pathogenesis of fibrotic diseases and is predominantly found in PaSCs through regulation by TGF-β. Pancreatic cancer cells also stimulate proliferation,