Artifactual insulin release from differentiated embryonic stem cells.

Abstract:

:Several recent reports claim the generation of insulin-producing cells from embryonic stem cells via the differentiation of progenitors that express nestin. Here, we investigate further the properties of these insulin-containing cells. We find that although differentiated cells contain immunoreactive insulin, they do not contain proinsulin-derived C-peptide. Furthermore, we find variable insulin release from these cells upon glucose addition, but C-peptide release is never detected. In addition, many of the insulin-immunoreactive cells are undergoing apoptosis or necrosis. We further show that cells cultured in the presence of a phosphoinositide 3-kinase inhibitor, which previously was reported to facilitate the differentiation of insulin(+) cells, are not C-peptide immunoreactive but take up fluorescein isothiocyanate-labeled insulin from the culture medium. Together, these data suggest that nestin(+) progenitor cells give rise to a population of cells that contain insulin, not as a result of biosynthesis but from the uptake of exogenous insulin. We conclude that C-peptide biosynthesis and secretion should be demonstrated to claim insulin production from embryonic stem cell progeny.

journal_name

Diabetes

journal_title

Diabetes

authors

Hansson M,Tonning A,Frandsen U,Petri A,Rajagopal J,Englund MC,Heller RS,Håkansson J,Fleckner J,Sköld HN,Melton D,Semb H,Serup P

doi

10.2337/diabetes.53.10.2603

subject

Has Abstract

pub_date

2004-10-01 00:00:00

pages

2603-9

issue

10

eissn

0012-1797

issn

1939-327X

pii

53/10/2603

journal_volume

53

pub_type

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