By: Neva Marjory

Neva Marjory — Mon, 24 Nov 2003 12:24:09 +0000

Tue Jul 15, 8:00 PM ET
Source: New York University Medical Center
In a finding that may open a new avenue to treating diabetes,
researchers show that cells from the bone marrow give rise to insulin-
producing cells in the pancreas of mice. These morphed cells actually
produce the hormone insulin in response to glucose and display other
characteristics demonstrating that they truly function as pancreas
cells, according to a new study by researchers from NYU School of
Medicine.
The study is published in the March 14 issue of the Journal of
Clinical Investigation. The researchers caution that the findings
cannot be applied to treating diabetics (news - web sites) now, but
may one day provide a means to produce unlimited quantities of
functional insulin-producing cells culled from the bone marrow of
diabetes patients. Since patients would produce their own cells for

transplantation, it is possible that the cells would not be rejected
by their immune system.
“Clearly much work remains to be done,” says Mehboob A. Hussain,
M.D., Assistant Professor of Medicine and Pharmacology, who led the
study. “But I am absolutely excited by the potential applications of
our findings,” he says. “In our body, there is an additional, easily
accessible source of cells that are capable of becoming insulin-
producing pancreatic endocrine cells. Transplantation of bone marrow
stem cells already is a routine procedure for treating cancer and
other diseases, and we could build on that experience.”
Dr. Hussain’s study is described as “elegant” in an accompanying
editorial by Drs. Vivian Lee and Markus Stoffel, two diabetes
researchers from The Rockefeller University, published in the same
issue of the journal. Dr. Hussain used a molecular biology technique
called “CRE-loxP” that allowed him to identify and isolate bone
marrow derived cells and to study them more closely than had
previously been possible.
One of the longstanding goals of diabetes research is to find a way
to replace the insulin-producing cells in the pancreas that are
damaged or destroyed in some forms of diabetes. These cells are
called beta cells and they are found in cell groups called islets of
Langerhans in the pancreas. In recent years doctors have reported
that they successfully transplanted pancreatic islets from cadavers
into some severely ill diabetics, most of whom were subsequently
freed from daily insulin shots. Insulin regulates blood sugar levels.
Immunosuppressive drugs were required to prevent rejection of the
transplants.
However, the supply of islets from cadavers is extremely limited, so
medical researchers are looking elsewhere. Several research groups
have reported that embryonic stem cells and cells found in the
pancreas (other than beta cells) could be converted into insulin-
producing cells, but until now no one had specifically explored the
bone marrow as a source of beta cells. (The bone marrow normally
replenishes blood cells and in recent years researchers have shown
that stem cells from the marrow can become cells of other organs.)
The CRE-loxP system is a sort of DNA editing technique that molecular
biologists widely employ to engineer genes. In the new study, Dr.
Hussain used the system to ingeniously create male mice with bone
marrow cells that produce a protein called enhanced green fluorescent
protein (EGFP) only in the presence of activated insulin genes, which
are typically found in pancreatic beta cells. EGFP imparts a green
glow to cells, which makes it easy to identify them. He then
transplanted the bone marrow from these males into female mice whose
bone marrow had been destroyed by radiation.
After four to six weeks, Dr. Hussain detected a small number of the
glowing green cells in the pancreatic islets of Langerhans of the
female mice. Further analysis showed that these cells came from the
bone marrow and functioned as the insulin-producing beta cells. These
cells all contained the Y chromosome, which could only have come from
the male donor. The cells also secreted insulin in response to
glucose, one of the signatures of pancreatic beta cells, and
exhibited electrical activity and other properties of beta cells.
Moreover, a second set of experiments showed that these bone marrow
derived cells were unlikely to be a result of cells fusing together.
Some researchers have suggested that the conversion of stem cells
into differentiated tissue is not real, but is due to artifacts of
experimental design produced by the fusion of Y chromosome-bearing
cells with host cells already present in the tissue. However, in the
second set of experiments, Dr. Hussain used the CRE-loxP system to
demonstrate that transplanted Y-chromosome bone marrow stem cells are
not fusing with pancreas cells in female recipient mice.
Despite the promising results, there are caveats to the study. Only
1.7 to 3 percent of beta cells in the pancreas of the female mice
came from transformed bone-marrow stem cells, a small number, and it
isn’t known which subpopulation of stem cells in the bone marrow are
the actual source of insulin-producing cells. Furthermore, it isn’t
known what happens in diabetic mice after bone marrow
transplantation. Dr. Hussain has proceeded with similar studies in
diabetic mice and with experiments that could help clarify how bone
marrow stem cells become beta cells in the pancreas.
“Our study isn’t the final proof,” says Dr. Hussain. “We still need
to find out how well these converted cells are functioning compared
to indigenous beta cells in the pancreas. A lot more work needs to be
done. Nevertheless, our study demonstrates the potential for using
the bone marrow as a source of insulin-producing cells.”
The experiments in the study were performed at NYU School of Medicine
and Dr. Hussain’s co-authors are Drs. I. Andreea Ianus, George G.
Holz and Neil D. Theise. The study was supported by grants from the
National Institutes of Health (news - web sites), the American
Diabetes Association, and the Juvenile Diabetes Research Foundation.
Copyright © 2003 Acurian Inc. All Rights Reserved.

Comments on: Bone Marrow Stem Cells Are a Source of Insulin-Producing Cells

By: Neva Marjory