To support development of novel therapies for Cystic Fibrosis (CF), the Cell Models Core (Core C) of the University of North Carolina (UNC) CF Research and Translation Core Center provides multiple services and resources. These are available to UNC CF Center members, to other local investigators, and to the national and international CF translational medicine communities. As well as our traditional strengths providing normal and CF human and mouse airway epithelial cell air liquid interface cultures in systems reproducing important elements of the airway in vivo, we have responded to changing needs and priorities, providing enhanced resources for GI research, including intestinal organoids, planar intestinal epithelial cell preparations, and esophageal and pancreatic epithelial cells. We support the “conditionally reprogrammed cell” technique for small, minimally invasive specimens, directed differentiation of induced pluripotent stem cells, genetic manipulation of primary cells for mechanistic studies and creation of novel cell lines. A fee-for-service Recharge for Service Center (RSC) for more convenient and wider provision of Core C services has been established. We are philosophically committed to widespread translation of non-proprietary technology locally, nationally and internationally by providing training and cell procurement and characterization services to outside suppliers of tissue specimens. The Cell Models Core, along with the other Cores in this proposal, will facilitate rapid, rigorous and reproducible research and pre-clinical testing necessary to overcome the significant barriers of bench to bedside translation of novel CF therapies.