From: Brett Paatsch (paatschb@optusnet.com.au)
Date: Wed May 07 2003 - 18:47:57 MDT
Genetically Modified Stem Cells Prevent Juvenile Diabetes in Mice
NEW YORK, May 7 /PRNewswire/ -- The Juvenile Diabetes Research Foundation International (JDRF) announced today that researchers at the JDRF Center for Immunoregulation at the Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia are reporting a new method for preventing juvenile (type 1) diabetes in mice that signals the immune system not to attack its insulin-secreting beta cells. This finding, published in the Journal of Clinical Investigation on May 1, 2003 may have great potential for the prevention of autoimmune diseases in humans.
Dr. Raymond Steptoe and Professor Leonard Harrison showed that stem cells could be manipulated so that immune cells that developed in their presence would not cause diabetes in susceptible animals.
"Although this procedure has only been tried in animals, it is encouraging that the method proved so effective at completely preventing juvenile (type 1) diabetes," stated Robert Goldstein, MD, PhD, Chief Scientific Officer, JDRF. "The study showed that you could teach the immune system not to attack the body. This tolerance is the goal for preventing all autoimmune disease, including juvenile diabetes. This exciting study is important proof of principle that should be supported in further trials."
The researchers used two groups of nonobese diabetic (NOD) mice: The NOD mouse is an animal model of spontaneous juvenile diabetes. One group remained unaltered, "wild-type", and the other was genetically altered so that proinsulin -- a protein normally made only by the pancreatic beta cells and a target of the immune attack in juvenile diabetes -- was expressed in the hematopoietic stem cells. Engineering proinsulin expression in the hematopoeitic stem cells was the critical modification. The hematopoietic stem cells then develop into different immune cells, including antigen-presenting cells (APCs). The expression of proinsulin in these (APCs) as they develop allows these cells to present fragments of the proinsulin protein to T cells in the absence of activation signals. This makes the T cells tolerant and unresponsive to the proinsulin in the pancreas. The T cells then regard the proinsulin-expressing beta cells as 'friendly.'
Relying on this mechanism, researchers transplanted bone marrow or hematopoietic stem cells from the altered mice into the wild-type NOD mice, whose bone marrow system had been destroyed by irradiation. Ordinarily, wild-type NOD mice develop diabetes efficiently. However, diabetes was almost completely prevented in mice receiving the proinsulin expressing bone marrow cells, and it was totally prevented in recipients of proinsulin expressing hematopoeitic stem cells. The effectiveness of the latter is especially promising since altering the hematopoeitic stem cells of a patient with juvenile diabetes would be a safer way to induce immune tolerance and possibly prevent the disease occurring in those at risk.
In juvenile diabetes, the production of insulin is eliminated when the autoimmune response destroys the insulin-producing beta cells in the pancreas. It strikes children and adults suddenly, makes them insulin-dependent for life, and carries with it the constant threat of complications.
JDRF, the leading charitable funder and advocate of juvenile (type 1) diabetes research worldwide, was founded in 1970 by the parents of children with juvenile diabetes -- a disease which strikes children suddenly, makes them insulin-dependent for life, and carries the constant threat of devastating complications. Since inception, JDRF has provided more than $600 million in direct funding to diabetes research. In a typical year, 85 percent of JDRF's expenditures directly support research and research-related education. JDRF's mission is constant: to find a cure for diabetes and its complications through the support of research. For more information, visit the JDRF web site at www.jdrf.org or call 800-533-CURE.
SOURCE Juvenile Diabetes Research Foundation International
This archive was generated by hypermail 2.1.5 : Wed May 07 2003 - 18:58:45 MDT