Generation of β Cells from iPSC of a MODY8 Patient with a Novel Mutation in the Carboxyl Ester Lipase (<i>CEL</i>) Gene

Abstract Context Maturity-onset diabetes of the young (MODY) 8 is a rare form monogenic characterized by mutation in CEL (carboxyl ester lipase) gene, which leads to exocrine pancreas dysfunction, followed β cell failure. Induced pluripotent stem cells can differentiate into functional cells. Thus, from MODY8 patients be generated vitro and used for disease modelling replacement therapy. Methods A genetic study was performed patient suspected diabetes. Results novel heterozygous pathogenic variant (c.1818delC) identified proband, allowing diagnosis MODY8. Three MODY8-iPSC (induced cell) clones were reprogrammed skin fibroblasts patient, their pluripotency genomic stability confirmed. All 3 differentiated following developmental stages. MODY8-iPSC–derived able secrete insulin upon glucose dynamic perifusion. The gene not expressed iPSCs nor during any steps endocrine differentiation. Conclusion iPSC lines with generated; they are capable differentiation cells, function preserved mutated These results set basis potentially autologous replacement.