In the complex progression of fibrosis in chronic pancreatitis, pancreatic stellate cells (PSCs) emerge as central figures. These cells, initially in a dormant state characterized by the storage of vitamin A lipid droplets within the chronic pancreatitis microenvironment, undergo a profound transformation into an activated state, typified by the secretion of an abundant extracellular matrix, including α-smooth muscle actin (α-SMA). This review delves into the myriad factors that trigger PSC activation within the context of chronic pancreatitis. These factors encompass alcohol, cigarette smoke, hyperglycemia, mechanical stress, acinar cell injury, and inflammatory cells, with a focus on elucidating their underlying mechanisms. Additionally, we explore the regulatory factors that play significant roles during PSC activation, such as TGF-β, CTGF, IL-10, PDGF, among others. The investigation into these regulatory factors and pathways involved in PSC activation holds promise in identifying potential therapeutic targets for ameliorating fibrosis in chronic pancreatitis. We provide a summary of recent research findings pertaining to the modulation of PSC activation, covering essential genes and innovative regulatory mediators designed to counteract PSC activation. We anticipate that this research will stimulate further insights into PSC activation and the mechanisms of pancreatic fibrosis, ultimately leading to the discovery of groundbreaking therapies targeting cellular and molecular responses within these processes.

Mesenchymal stem cells (MSCs) have demonstrated potential in both clinical and pre-clinical research for mitigating tissue damage and inflammation associated with acute pancreatitis (AP) via paracrine mechanisms. Hence, there has been a recent surge of interest among researchers in utilizing MSC cultured medium (CM) and its components for the treatment of AP, which is recognized as the primary cause of hospitalization for gastrointestinal disorders globally. A systematic review was conducted by searching the MEDLINE, EMBASE, and Web of Science databases. Studies that involve the administration of MSC-CM, extracellular vesicles/microvesicles (EVs/MVs), or exosomes to AP animal models are included. A total of six research studies, including eight experiments, were identified as relevant. The findings of this study provide evidence in favor of a beneficial impact of MSC-CM on both clinical and immunological outcomes. Nevertheless, prior to clinical trials, large animal models should be used and prolonged observation periods conducted in pre-clinical research. Challenges arise due to the lack of standardization and consensus on isolation processes, quantifications, and purity testing, making it difficult to compare reports and conduct meta-analyses in MSC-CM-based therapies.