MODELING PANCREATIC PATHOPHYSIOLOGY USING GENOME EDITING OF ADULT STEM CELL- AND INDUCED PLURIPOTENT STEM CELL (iPSC)-DERIVED ORGANOIDS

In recent years, organoids have become a novel in vitro method to study gastrointestinal organ development, physiology and disease. An organoid, in short, may be defined as a miniaturized organ that can be grown from adult stem cells in vitro and studied at the microscopic level. Organoids have been used in multitudes of different ways to study the physiology of different human diseases including gastrointestinal cancers such as pancreatic cancer. The development of genome editing based on the bacterial defense mechanism CRISPR/Cas9 has emerged as laboratory tool that provides the opportunity to study the effects of specific genetic changes on organ development, physiology and disease. The CRISPR/Cas9 approach can be combined with organoid technology including the use of induced pluripotent stem cell (iPSC)-derived and tissue-derived organoids. The goal of this review is to provide highlights on the development of organoid technology, and the use of this culture system to study the pathophysiology of specific mutations in the development of pancreatic and gastric cancers.