Stem
Cell Transplant Prevents Autoimmune Diabetes
Syngeneic transplant of hematopoietic stem cells
(HSCs) encoding proinsulin antigen prevents autoimmune
diabetes.
That,
according to a report in the May issue of The
Journal of Clinical Investigation.
Proinsulin is a key autoantigen that drives pancreatic
beta cell destruction in type 1 diabetes, the
authors explain, suggesting that induction of
tolerance to proinsulin might prevent autoimmune
diabetes.
Dr. Leonard Harrison and associates from The Walter
and Eliza Hall Institute of Medical Research in
Parkville, Victoria, Australia tested whether
HSCs from NOD mice in which proinsulin was transgenically
targeted to antigen-presenting cells could prevent
autoimmune diabetes when transplanted into wild-type
NOD mice.
Diabetes was almost completely prevented in recipients
of bone marrow from NOD mice bred to encode proinsulin
(1 of 16 mice developed diabetes), the authors
report, whereas 15 of 23 untreated controls and
in 7 of 12 recipients of normal NOD bone marrow
developed diabetes.
T cell depletion of transplanted bone marrow did
not reduce the protective effect of cells encoding
proinsulin.
Similarly, diabetes was completely prevented in
recipients of proinsulin-encoding HSCs (0 of 10
mice developed diabetes), the results indicate.
Transfer of hematopoietic progenitor cells also
afforded substantial protection (2 of 14 mice
developed diabetes, compared with 8 of 16 controls).
"Complete protection after transfer of highly
purified HSCs shows that diabetes prevention depends
on the engraftment of multipotent hematopoietic
cells and not on the inadvertent transfer of immunoregulatory
cells in whole of T cell-depleted bone marrow,"
the researchers explain.
The protective effect of HSC or bone marrow transplantation
was evident even at low levels of bone marrow
engraftment, the investigators observe.
"These results are a proof of principle that
autoantigen-expressing HSCs can be used as a therapeutic
tool to prevent autoimmune disease," the
authors conclude. "We envisage that HSCs
could be harvested from peripheral blood of at-risk
individuals, genetically modified to encode autoantigen,
and reinfused to prevent autoimmune disease."
J Clin Invest 2003;111:1357-1363.
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DID
YOU KNOW: The results from a review
of Medicare claims from 13,660 diabetic patients
who received regular outpatient care from a primary
care physician (n = 1,749). during a 24-month
period, 31% received no lipid profile, 24% received
only one lipid profile, and 45% of the diabetic
patients received two or more lipid profiles.
Diabetes Care May 2003