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[IP] Bone Marrow Stem Cells Are a Source of Insulin-Producing Cells

Bone Marrow Stem Cells Are a Source of Insulin-Producing Cells
March 27, 2003, Acurian

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 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 them 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

"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, the American Diabetes Association, and
the Juvenile Diabetes Research Foundation.

Copyright ) 2003 Acurian Inc. All Rights

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