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This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 39/1/72    most recent 00063.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Kutlu, B. Articles by Hood, L. PubMed PubMed Citation Articles by Kutlu, B. Articles by Hood, L.

Meta-analysis of gene expression in human pancreatic islets after in vitro expansion

¹ Institute for Systems Biology, Seattle, Washington
² Whittier Institute/Department of Pediatrics, University of California at San Diego, La Jolla, California
³ The University of Calgary, Calgary, Canada
⁴ Centre Médical Universitaire, Geneva, Switzerland

Pancreatic islet transplantation as a potential cure for type 1 diabetes (T1D) cannot be scaled up due to a scarcity of human pancreas donors. In vitro expansion of β-cells from mature human pancreatic islets provides an alternative source of insulin-producing cells. The exact nature of the expanded cells produced by diverse expansion protocols and their potential for differentiation into functional β-cells remain elusive. We performed a large-scale meta-analysis of gene expression in human pancreatic islet cells, which were processed using three different previously described protocols for expansion and for which redifferentiation was attempted. All three expansion protocols induced dramatic changes in the expression profiles of pancreatic islets; many of these changes are shared among the three protocols. Attempts at redifferentiation of expanded cells induce a limited number of gene expression changes. Nevertheless, these fail to restore a pancreatic islet-like gene expression pattern. Comparison with a collection of public microarray datasets confirmed that expanded cells are highly comparable to mesenchymal stem cells. Genes induced in expanded cells are also enriched for targets of transcription factors important for pluripotency induction. The present data increase our understanding of the active pathways in expanded and redifferentiated islets. Knowledge of the mesenchymal stem cell potential may help development of drug therapeutics to restore β-cell mass in T1D patients.

regeneration; differentiation; mesenchymal stem cells