Advanced donor age reduces quality of islet cells used in transplantation
Experiments in diabetic mice have demonstrated that the age of islet cell donors affects the efficacy of transplants, transplant surgeons at the University of Minnesota, Minneapolis, report.
In a study published in the May issue of Diabetes, Dr. Bernhard J. Hering and colleagues analyzed human islet cells taken from 93 cadaveric donors ranging in age from 16 to 70 years, and transplanted into diabetic mice. They found that diabetes reversal occurred in nearly 100% of diabetic mice receiving islet cells harvested from human donors less than 40 years of age. In contrast, diabetes reversal occurred in approximately two-thirds of recipients of islet cells from donors aged 40 and older.
The investigators measured glucose-stimulate insulin response (GSIR), islet ATP levels, C-peptide changes on glucose tolerance testing (GTT) conducted at 90-120 days after transplantation and diabetes reversal rates with islet cell transplantation.
Diabetes reversal rate was 96% in younger donors and 68% in older donors. GSIR and C-peptide response to glucose correlated negatively with age. ATP levels averaged 75.7 pmol/microgram for donors aged 40 and older and 115.7 pmol/microgram in younger donors.
Dr. Hering speculates that the age-related deterioration in regulation of insulin secretion on glucose exposure may be related to decreasing ATP generation in beta cells. It also appears that the success rate with transplantation of aging islet cells appears to require harvesting a larger islet mass. However, using multiple donors to obtain a large enough islet mass has not be shown to be effective, the investigators point out.
