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^ Majumdar, M. K., et al., “Characterization and functionality of cell surface molecules 
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^ Soria, B., et al., "Insulin-secreting cells derived from embryonic stem cells normalize 
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^ Lechner, A. and Habener, J. F., "Stem/progenitor cells derived from adult tissues: 
potential for the treatment of diabetes mellitus," American Journal of Physiology - 
Endocrinology and Metabolism 284: E259-266 (2003). The criteria that these authors 
outlined were as follows: 
• The stem or progenitor cell should be clonally isolated or marked; "en- 
richment” of a certain cell type alone is not sufficient. 
• In vitro differentiation to a fully functional beta cell should be unequivo- 
cally established. Insulin expression per se does not make a particular 
cell a beta cell. The expression of other markers of beta cells (e.g. 
Pdxl/Ipfl, GLUT2, and glucokinase) or other endocrine islet cells 
should be demonstrated. 
• Ultrastructural studies should confirm the formation of mature endo- 
crine cells by identification of characteristic insulin secretory granules. 
• The in vitro function of endocrine cells, differentiated from stem cells, 
should be reminiscent of the natural coimterparts. For beta cells, this 
would imply a significant glucose-respx5nsive insulin secretion, ade- 
quate responses to incretin hormones and secretagogues, and the ex- 
pected electrophysiological properties. 
• In vivo studies in diabetic einimals shoiold demonstrate a reproducible 
and durable effect of the stem/progenitor-derived tissue on the attenua- 
tion of the diabetic phenotype. It should also be demonstrated that re- 
moval of the stem cell-derived graft after a certain period of time leads 
to reappearance of the diabetes. 
PRE -PUBLICATION VERSION 
