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: 2007-0164v1 25/11/2837    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 Karnieli, O. Articles by Efrat, S. Search for Related Content PubMed PubMed Citation Articles by Karnieli, O. Articles by Efrat, S.

TISSUE-SPECIFIC STEM CELLS

Generation of Insulin-Producing Cells from Human Bone Marrow Mesenchymal Stem Cells by Genetic Manipulation

^aDepartment of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv, Israel;
^bLaniado Medical Center, Nethanya, Israel

Key Words. β Cell replacement • Insulin secretion • Pancreatic duodenal homeobox 1 • Cell transplantation

Correspondence: Shimon Efrat, Ph.D., Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel. Telephone: 972-3-640-7701; Fax: 972-3-640-9950; e-mail: sefrat{at}post.tau.ac.il

Received on March 7, 2007; accepted for publication on June 26, 2007.

First published online in STEM CELLS EXPRESS  July 5, 2007.


β Cell replacement is a promising approach for treatment of type 1 diabetes; however, it is limited by a shortage of pancreas donors. The pluripotent MSC in adult bone marrow (BM) offer an attractive source of stem cells for generation of surrogate β cells. BM-MSC can be obtained with relative ease from each patient, allowing potential circumvention of allograft rejection. Here, we report a procedure for expansion of BM-MSC in vitro and their differentiation into insulin-producing cells. The pancreatic duodenal homeobox 1 (Pdx1) gene was expressed in BM-MSC from 14 human donors, and the extent of differentiation of these cells toward the β-cell phenotype was evaluated. RNA and protein analyses documented the activation of expression of all four islet hormones. However, the cells lacked expression of NEUROD1, a key transcription factor in differentiated β cells. A significant insulin content, as well as glucose-stimulated insulin release, were demonstrated in vitro. Cell transplantation into streptozotocin-diabetic immunodeficient mice resulted in further differentiation, including induction of NEUROD1, and reduction of hyperglycemia. These findings were reproducible in BM-MSC from 9 of 14 donors of both sexes, ages 19–62. These results suggest a therapeutic potential for PDX1-expressing BM-MSC in β-cell replacement in patients with type 1 diabetes.

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

This article has been cited by other articles:

				M Mimeault and S K Batra Recent progress on normal and malignant pancreatic stem/progenitor cell research: therapeutic implications for the treatment of type 1 or 2 diabetes mellitus and aggressive pancreatic cancer Gut, October 1, 2008; 57(10): 1456 - 1468. [Abstract] [Full Text] [PDF]

				B. Davani, L. Ikonomou, B. M. Raaka, E. Geras-Raaka, R. A. Morton, B. Marcus-Samuels, and M. C. Gershengorn Human Islet-Derived Precursor Cells Are Mesenchymal Stromal Cells That Differentiate and Mature to Hormone-Expressing Cells In Vivo Stem Cells, December 1, 2007; 25(12): 3215 - 3222. [Abstract] [Full Text] [PDF]