Stem cells: From bone marrow to pancreas

Diabetes is the consequence of an inadequate functional mass of insulin-producing cells -- so called beta cells -- in the pancreas. In type 1 diabetes, the body's immune system mistakenly attacks and destroys these beta cells. In type 2 diabetes, often associated with obesity, beta cells are present but fail to secrete enough insulin to ensure normal energy metabolism. Results from animal studies and early human clinical trials suggest that transplantation of beta cells can be beneficial in type 1 and type 2 diabetes. But there is clearly insufficient material from human donors for the increasing number of diabetic patients, and the side effects from immunosuppressive drugs that transplantation patients have to take are severe. Scientists have therefore looked for other sources of beta cells, specifically for stem cells that could be expanded and induced to become beta cells. Mouse embryonic stem cells can develop into insulin-secreting cells, and cells with the potential to become beta cells also exist in the pancreas itself and in the liver. Mehboob Hussain and colleagues (New York University, New York) now report that, at least in mice, the bone marrow also contains cells that can become functional beta cells.

The paper, published in the March 14 issue of the Journal of Clinical Investigation, presents elegant experiments that involve transplantation of bone marrow cells from a male donor mouse to a female recipient. The cells were engineered such that they became fluorescent if the insulin gene is switched on. Hussain and colleagues found male cells (marked by the presence of the Y chromosome) in the pancreas of recipient female mice. These cells were fluorescent – which means that they had developed into insulin-expressing cells--and looked and behaved like functional beta cells based on a variety of other assays. Some previous claims of pluripotent adult stem cells have been undermined by cell fusion events during which a transplanted bone marrow cell fuses with existing beta cells. Taking further advantage of the power to genetically engineer and mark cells in mice, the scientists designed a second experiment that allowed them to exclude that the fluorescent beta-like cells resulted from such events.

Markus Stoffel, a diabetes expert at Rockefeller University, New York City, who discusses the findings and their implications in an accompanying commentary, suggests that "the use of bone marrow as a source of pancreatic beta-cell precursors has the potential for ex vivo expansion, differentiation, and autologous transplantation".

**Please mention the Journal of Clinical Investigation as the source of this article**

CONTACT:
Pamela McDonnell
Office of Public Affairs
NYU School of Medicine
Phone: 212-404-3555
Fax: 212-404-3570
E-mail: Pamela.McDonnell@med.nyu.edu

View the PDF of this article at: http://www.jci.org/cgi/content/full/111/6/843

ACCOMPANYING COMMENTARY:
Bone marrow: An extrapancreatic hideout for the elusive pancreatic stem cell?

CONTACT:
Markus Stoffel
Rockefeller University
Laboratory of Metabolic Diseases
1230 York Avenue, Box 292
New York, NY 10021
USA
PHONE: 212-327-8797
FAX: 212-327-7997
E-mail: stoffel@rockvax.rockefeller.edu

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