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Related Experiment Videos

Artifactual insulin release from differentiated embryonic stem cells.

Mattias Hansson1, Anna Tonning, Ulrik Frandsen

  • 1Department of Developmental Biology, Hagedorn Research Institute, Niels Steensens vej 6, DK-2820 Gentofte, Denmark.

Diabetes
|September 28, 2004
PubMed
Summary

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Embryonic stem cell-derived cells contain insulin but lack C-peptide, suggesting exogenous uptake, not biosynthesis. Demonstrating C-peptide is crucial for claiming insulin production from stem cell progeny.

Area of Science:

  • Stem cell biology
  • Endocrinology
  • Cellular differentiation

Background:

  • Recent studies report generating insulin-producing cells from embryonic stem cells.
  • These cells originate from nestin-expressing progenitor cells.

Purpose of the Study:

  • To investigate the properties of insulin-containing cells derived from embryonic stem cells.
  • To determine if these cells genuinely produce insulin via biosynthesis.

Main Methods:

  • Immunoreactivity assays for insulin and C-peptide.
  • Glucose-stimulated insulin and C-peptide release measurements.
  • Apoptosis and necrosis assessments.
  • Cell culture with phosphoinositide 3-kinase inhibitors and exogenous insulin uptake studies.

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Main Results:

  • Differentiated cells showed insulin immunoreactivity but lacked C-peptide.
  • Variable insulin release was observed, but C-peptide release was never detected.
  • Many insulin-immunoreactive cells exhibited signs of apoptosis or necrosis.
  • Cells treated with a phosphoinositide 3-kinase inhibitor took up exogenous insulin and lacked C-peptide.

Conclusions:

  • Nestin-positive progenitor cells yield cells containing insulin through exogenous uptake, not biosynthesis.
  • Claiming insulin production from embryonic stem cell progeny requires demonstrating C-peptide biosynthesis and secretion.