insulin cells reproduced

December 3, 2008

Researchers Identify New Source of Insulin-Producing Cells

Researchers at the Joslin Diabetes Center have shown that insulin-producing

pancreatic beta cells can form after birth or after injury from progenitor

cells

within the pancreas that were not beta cells, a finding that contradicts a

widely-cited earlier study that had concluded this is not possible.

The published study, identifies the source of the progenitor cells as being

pancreatic duct cells. This means that there is a population of pancreatic

cells

that can be stimulated, either within the body or outside the body, to

become new beta cells, the cells that are lacking in diabetes, " said

Bonner-Weir,

Ph.D., the study's lead researcher and a Senior Investigator in the Section

on Islet Transplantation and Cell Biology at Joslin and Associate Professor

of Medicine at Harvard Medical School.

The experiments, conducted in animal models, suggest a new source of beta

cells for replacement therapy to treat or cure diabetes.

In type 1 diabetes, the pancreas produces little or no insulin since the

insulin producing beta cells are destroyed by the body's own immune system..

While

transplantation of human islets from donor pancreases has been successful in

getting people with type 1 diabetes off insulin treatment, this insulin

independence

is only successful for a few years.

" One of the problems with islet transplantation is that while the proof of

principal is there, we don't have enough islets to transplant and they go

through

a traumatic process during isolation, " said Bonner-Weir. " Many islets are

not in the greatest condition after being isolated from a pancreas. "

The two major obstacles to islet transplants are the need for continued use

of immunosuppressive drugs to prevent both rejection and return of

autoimmune

destruction and the lack of a reliable source of insulin producing islet

cells.

Bonner-Weir's main research focus is the search for new sources of

insulin-producing islet cells. In this study, in experiments in mice,

Bonner-Weir's

group used a similar lineage tracing system employed by a group from Dr.

Melton's lab at Harvard. That group concluded in a paper published

in

Nature in 2004 that after birth, new beta cells only result from division of

preexisting beta cells and that beta cells do not form from progenitor cells

after birth.

" That conclusion, coming from such a well-respected group, was taken by many

as fact and cast a cloud over this important research area, " Bonner-Weir

said.

However, earlier this year a group led by Xiaobo Xu in Belgium showed that

islet progenitor cells within the adult pancreas could be activated to

increase

the number of beta cells by the process of differentiation rather than

self-duplication, but the paper did not indicate the origin of these cells.

Bonner-Weir's paper complements the Belgium study by identifying the source

of these cells as pancreatic duct cells.

In addition to finding that these duct cells can differentiate into insulin

producing islet cells after birth and in regeneration after injury, the

study

showed that they can also become new acinar cells, a finding that has

potential implications for pancreatic cancer, since the origin of the

cancerous cells

has been disputed.

Two lineage tracing experiments involved genetically marking the ductal

cells and then following them. The first experiment, which involved

one-month-old

mice, found that between 30 to 40 percent of islets had beta cells that had

formed after birth from duct cells. In the second experiment, conducted in

adult mice, the Joslin researchers used same regeneration model employed in

the Belgian study which is based on tying off the main pancreatic duct.

Beyond

the area of the tie some cells die, but others grow to regenerate the whole

structure. In these adult mice, new islets and new acinar cells were again

shown to have been formed from the preexisting duct cells.

" Our data provide strong support to the concept of a shared lineage of

ductal, acinar and islet cells after birth, even in the adult. This means

that there

is a population of cells - we don't know if it is all of the cells or just

some - that can be stimulated to become new islet cells, " Bonner-Weir said.

She concluded: " Our identification of a differentiated pancreatic cell type

as an in vivo progenitor for all differentiated pancreatic cell types has

implications

for a potential expandable source for new islets for replacement therapy for

diabetes. While the ideal therapy would be to have those with diabetes

regenerate

their own islet cells, that is still a long way off. "

online Proceedings of the National Academy of Sciences Early Edition,

November 25th, 2008

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This article originally posted December 2, 2008 and appeared in

Issue 445

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