Reversal of hyperglycemia in mice by using human expandable insulin-producing cells differentiated from fetal liver progenitor cells

Michal Zalzman, Sanjeev Gupta, Ranjit K. Giri, Irina Berkovich, Baljit S. Sappal, Ohad Karnieli, Mark A. Zern, Norman Fleischer, Shimon Efrat

Research output: Contribution to journalArticlepeer-review

247 Scopus citations

Abstract

Beta-cell replacement is considered to be the most promising approach for treatment of type 1 diabetes. Its application on a large scale is hindered by a shortage of cells for transplantation. Activation of insulin expression, storage, and regulated secretion in stem/progenitor cells offers novel ways to overcome this shortage. We explored whether fetal human progenitor liver cells (FH) could be induced to differentiate into insulin-producing cells after expression of the pancreatic duodenal homeobox 1 (Pdx1) gene, which is a key regulator of pancreatic development and insulin expression in beta cells. FH cells possess a considerable replication capacity, and this was further extended by introduction of the gene for the catalytic subunit of human telomerase. Immortalized FH cells expressing Pdx1 activated multiple beta-cell genes, produced and stored considerable amounts of insulin, and released insulin in a regulated manner in response to glucose. When transplanted into hyperglycemic immunodeficient mice, the cells restored and maintained euglycemia for prolonged periods. Quantitation of human C-peptide in the mouse serum confirmed that the glycemia was normalized by the transplanted human cells. This approach offers the potential of a novel source of cells for transplantation into patients with type 1 diabetes.

Original languageEnglish (US)
Pages (from-to)7253-7258
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number12
DOIs
StatePublished - Jun 10 2003

ASJC Scopus subject areas

  • General

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