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TISSUE-SPECIFIC STEM CELLS

Enhanced Oxygenation Promotes β-Cell Differentiation In Vitro

^aDiabetes Research Institute, University of Miami Leonard M. Miller School of Medicine, Miami, Florida, USA;
^bDepartment of Biomedical Engineering, University of Miami, Coral Gables, Florida, USA

Key Words. Stem cells • Islets • Perfluorocarbon • Oxygenation • β Cells

Correspondence: Juan Domínguez-Bendala, M.Sc., Ph.D., Diabetes Research Institute, University of Miami Leonard M. Miller School of Medicine, 1450 NW 10th Avenue, Miami, Florida 33136, USA. Telephone: 305-243-4092; Fax: 05-243-4404; e-mail: jdominguez2{at}med.miami.edu

Received on June 7, 2007; accepted for publication on August 21, 2007.

First published online in STEM CELLS EXPRESS  August 30, 2007.


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.

Disclosure of potential conflicts of interest is found at the end of this article.