Type 1 diabetes

One Response to “Bone Marrow Stem Cells Are a Source of Insulin-Producing Cells”

1. Neva Marjory Says:
   November 24th, 2003 at 3:24 pm

   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.

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