Posted by Marina on July 04, 2001 at 13:07:08:
Cytoprotection of pancreatic islets before and soon after
transplantation by gene transfer of the anti-apoptotic Bcl-2 gene.
Contreras JL, Bilbao G, Smyth CA, Jiang XL, Eckhoff DE, Jenkins SM, Thomas FT, Curiel DT,
Thomas JM
Transplant Immunobiology Division, Transplant Center, University of Alabama at Birmingham, USA.
Isolated pancreatic islet transplantation is a promising alternative to conventional insulin-dependent
diabetes treatment but is not yet a practical clinical therapy. In the first few days after pancreatic islet
transplantation, substantial donor pancreatic islet dysfunction and apoptosis commonly occur. Islet
apoptosis has been documented after extracellular matrix disruption and exposure to proinflammatory
cytokines, and during hypoxia before islet revascularization and rejection. These studies show that targeting
the apoptosis pathway by adenoviral-mediated gene transfer of the anti-apoptotic Bcl-2 gene exerts a major
cytoprotective effect on isolated macaque pancreatic islets. Bcl-2 transfection ex vivo protects these islets
from apoptosis induced by disruption of the islet extracellular matrix during pancreatic digestion.
Additionally, overexpression of Bcl-2 confers long-term, stable protection and maintenance of functional
islet mass after transplantation of macaque islets into diabetic severe combined immunodeficency mice.
Notably, genetic modification of pancreatic islets also reduced the islet mass required to achieve stable
euglycemia. Ex vivo gene transfer of anti-apoptotic genes has potential as a therapeutic approach to both
minimize loss of functional islet mass after transplant and reduce the high donor islet requirement
currently needed for successful stable reversal of insulin-dependent diabetes.
PMID: 11374395, UI: 21267628