Generation of β cells from iPSC of a MODY8 patient with a novel mutation in the carboxyl ester lipase (CEL) gene.

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

View the full article @ The Journal of clinical endocrinology and metabolism

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