Enhanced oxygenation promotes β-cell differentiation in vitro

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

Research output: Contribution to journalArticle

39 Citations (Scopus)

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

Fingerprint

Cell Differentiation
Stem Cells
Fluorocarbons
Adult Stem Cells
Differentiation Antigens
Embryonic Stem Cells
Islets of Langerhans
Up-Regulation
Insulin
Equipment and Supplies
In Vitro Techniques

Keywords

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

ASJC Scopus subject areas

  • Cell Biology

Cite this

Enhanced oxygenation promotes β-cell differentiation in vitro. / Fraker, Christopher; Álvarez, Silvia; Papadopoulos, Panagiotis; Giraldo, Jaime; Gu, Weiyong; Ricordi, Camillo; Inverardi, Luca A; Dominguez-Bendala, Juan.

In: Stem Cells, Vol. 25, No. 12, 01.12.2007, p. 3155-3164.

Research output: Contribution to journalArticle

Fraker, Christopher ; Álvarez, Silvia ; Papadopoulos, Panagiotis ; Giraldo, Jaime ; Gu, Weiyong ; Ricordi, Camillo ; Inverardi, Luca A ; Dominguez-Bendala, Juan. / Enhanced oxygenation promotes β-cell differentiation in vitro. In: Stem Cells. 2007 ; Vol. 25, No. 12. pp. 3155-3164.
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