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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 June 7, 2007; accepted for publication 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.