Enhanced oxygenation promotes β-cell differentiation in vitro

Christopher A. Fraker, Silvia Álvarez, Panagiotis Papadopoulos, Jaime Giraldo, Weiyong Gu, Camillo Ricordi, Luca Inverardi, Juan Domínguez-Bendala

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Despite progress in our knowledge about pancreatic islet specification, most attempts at differentiating stem/progenitor cells into functional, transplantable β cells have met only with moderate success thus far. A major challenge is the intrinsic simplicity of in vitro culture systems, which cannot approximate the physiological complexity of in vivo microenvironments. Oxygenation is a critical limitation of standard culture methods, and one of special relevance for the development of β cells, known for their high O2 requirements. Based on our understanding of islet physiology, we have tested the hypothesis that enhanced O2 delivery (as provided by novel perfluorocarbon-based culture devices) may result in higher levels of β-cell differentiation from progenitor cells in vitro. Using a mouse model of pancreatic development, we demonstrate that a physiological-like mode of O2 delivery results in a very significant upregulation of endocrine differentiation markers (up to 30-fold for insulin one and 2), comparable to relevant in vivo controls. This effect was not observed by merely increasing environmental O2 concentrations in conventional settings. Our findings indicate that O2 plays an important role in the differentiation of β cells from their progenitors and may open the door to more efficient islet differentiation protocols from embryonic and/or adult stem cells.

Original languageEnglish (US)
Pages (from-to)3155-3164
Number of pages10
JournalStem Cells
Volume25
Issue number12
DOIs
StatePublished - Dec 1 2007

Keywords

  • β cells
  • Islets
  • Oxygenation
  • Perfluorocarbon
  • Stem cells

ASJC Scopus subject areas

  • Cell Biology

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