NATIONAL BIOREPOSITORY OF LUNG DISEASE-SPECIFIC HUMAN INDUCED PLURIPOTENT STEM CELLS:THE PURPOSE OF THIS RESOURCE IS TO BUILD AND SUPPORT A CRITICAL

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ABSTRACT This proposal seeks to support a formalized national resource for lung researchers consisting of a lung disease specific induced pluripotent stem cell (iPSC) biorepository that can be shared without restriction or exclusivity. More than 200 human lung disease-relevant iPSC lines, and their gene-edited progeny, are now banked in the Center for Regenerative Medicine (CReM) of Boston University/Boston Medical Center, providing an unprecedented opportunity for any basic scientist to derive an inexhaustible supply of patient-derived lung epithelial, vascular, immune, or interstitial cells. These cells containing each patient’s own genetic background are now available for in vitro human lung disease modeling, drug screening of personalized therapeutics, and the development of future lung regeneration cell-based therapies. The most valuable human clones in this bank not only carry the most common lung disease-inducing mutations (e.g. mutations in loci encoding CFTR, Alpha-1 antitrypsin, BMPR2, SFTPC, SFTPB, ABCA3, and NKX2.1), but also carry knock-in fluorochrome reporters targeted to specific loci through state-of-the-art gene editing technologies. We propose to make the biorepository available to all researchers through formalized mechanisms that ensure: a) national sharing of iPSCs that comprise a critical resource in high demand by both basic and clinical lung researchers, b) establishment of quality assurance approaches and methods for banking, curating, and maintaining an exhaustive panel of human lines carrying the most common gene mutations and lung lineage reporter genes required by the majority of U.S. lung researchers in the years ahead, and c) continuation of a formalized education and training program able to nationally disseminate the expertise required to fully harness these new tools and differentiate them into lung lineages.