Sustained proliferation of PDX-1+ cells derived from human islets

Gillian M. Beattie, Pamela Itkin-Ansari, Vincenzo Cirulli, Gil Leibowitz, Ana D. Lopez, Stuart Bossie, Martin I. Mally, Fred Levine, Alberto Hayek*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

134 Scopus citations

Abstract

Ex vivo expansion of human β-cells is an important step toward the development of cell-based insulin delivery systems in type 1 diabetes. Here, we report that human pancreatic endocrine cells can be expanded through 15 cell doublings in vitro for an estimated total 30,000-fold increase in cell number. We believe that the cells resulting from these cultures are of β- cell origin, since they uniformly express the transcription factor PDX-1 (STF-1, IDX-1, IPF-1), which is initially seen only in cells positive for insulin and negative for the ductal cell marker cytokeratin (CK)-19. To rule out the possibility that PDX-1 expression might be induced by the culture conditions used here, cells from isolated human pancreatic ducts were cultured under the same conditions as the islet cells. Cells in these cultures expressed CK-19 but not PDX-1. Although the expanded β-cells continued to express PDX-1, insulin expression was lost over time. Whether reexpression of islet-specific genes in vitro is essential for successful cell transplantation remains to be determined.

Original languageEnglish
Pages (from-to)1013-1019
Number of pages7
JournalDiabetes
Volume48
Issue number5
DOIs
StatePublished - 1999
Externally publishedYes

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