HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 2007-0762v1 26/5/1128    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Boyd, A. S. Articles by Wood, K. J. Search for Related Content PubMed PubMed Citation Articles by Boyd, A. S. Articles by Wood, K. J.

EMBRYONIC STEM CELLS

A Comparison of Protocols Used to Generate Insulin-Producing Cell Clusters from Mouse Embryonic Stem Cells

Transplantation Research Immunology Group, Nuffield Department of Surgery, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom

Key Words. ESC • Differentiation • Insulin-secreting cells • In vitro differentiation • Cell transplantation • Pancreatic differentiation • ES cells • Diabetes

Correspondence: Ashleigh S. Boyd, D.Phil., Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, United Kingdom. Telephone: +44 1865 275 606; Fax: +44 1865 275 515; e-mail: ashleigh.boyd{at}path.ox.ac.uk

Received September 11, 2007; accepted for publication February 18, 2008.
First published online in STEM CELLS EXPRESS   March 6, 2008.



Embryonic stem cells (ESCs) have the capacity to generate a panoply of tissue types and may therefore provide an alternative source of tissue in regenerative medicine to treat potentially debilitating conditions like Type 1 diabetes mellitus. However, the ability of mouse ESCs to generate insulin-producing cell clusters (IPCCs) remains highly contentious. In an attempt to clarify this issue, three protocols for the ESC-based generation of IPCCs (referred to as Blyszczuk, Hori, and Lumelsky protocols) were modified and evaluated for their ability to express pancreatic islet genes and proteins and their capacity to function. Herein, we show that the Blyszczuk protocol reproducibly generated IPCCs with gene-expression characteristics that were qualitatively and quantitatively most reminiscent of those found in pancreatic islets. Furthermore, compared to the Hori and Lumelsky protocols, Blyszczuk-derived IPCCs exhibited superior expression of c-peptide, a by-product of de novo insulin synthesis. Functionally, Blyszczuk IPCCs, in contrast to Hori and Lumelsky IPCCs, were able to transiently restore normal blood glucose levels in diabetic mice (<1 week). Longer normoglycemic rescue (>2 weeks) was also achieved in a third of diabetic recipients receiving Blyszczuk IPCCs. Yet Blyszczuk IPCCs were less able to rescue experimental diabetes than isolated syngeneic pancreatic islet tissue. Therefore, depending on the mode of differentiation, ESCs can be driven to generate de novo IPCCs that possess limited functionality. Further modifications to differentiation protocols will be essential to improve the generation of functional IPCCs from mouse ESCs.

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

This article has been cited by other articles:

				M. L. Condic and M. Rao Regulatory Issues for Personalized Pluripotent Cells Stem Cells, November 1, 2008; 26(11): 2753 - 2758. [Abstract] [Full Text] [PDF]

				D. C. Wu, A. S. Boyd, and K. J. Wood Embryonic Stem Cells and Their Differentiated Derivatives Have a Fragile Immune Privilege but Still Represent Novel Targets of Immune Attack Stem Cells, August 1, 2008; 26(8): 1939 - 1950. [Abstract] [Full Text] [PDF]