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In vitro studies have demonstrated that beta-cell functions are negatively influenced by age and positively by the presence of glucagon producing alpha cells. This study examines whether the function of beta-cell grafts varies with the age of the donor and with the presence of other endocrine islet cells. Islet beta and endocrine non-beta-cells were purified from 10- to 30-week-old Lewis rats, and reaggregated into pure beta and mixed endocrine cell aggregates. Grafts consisted of 1.2 to 1.7 million beta cells with or without 0.6-0.7 million alpha cells. Their intraportal transplantation in 10-week-old streptozotocin-diabetic rats corrected hyperglycaemia in all experimental groups, with normal glucose tolerance curves at post-transplantation week (PT wk) 4. Recipients of mixed endocrine cell grafts from 10-week-old donors maintained a glucose tolerant state until PT wk 20, but turned glucose intolerant thereafter; only 1 of 12 animals was overtly diabetic at PT wk 64. Recipients of pure beta-cell grafts from 10-week-old donors became glucose-intolerant from PT wk 4 on, with 5 of 11 cases developing overt diabetes before PT wk 64. When grafts were prepared from 30-week-old donors, metabolic deterioration started earlier, again with a more rapid loss for pure beta-cell grafts; at PT wk 64, virtually all recipients were overtly diabetic. It is concluded that delayed graft failure can be the consequence of an insufficient number of islet endocrine non-beta-cells as well as of a higher donor age. This observation can explain late failures in animal and human islet transplantation using marginally low beta-cell numbers. The interpretation of long-term studies on islet cell transplantation can benefit from the use of standardized grafts with well defined cellular composition.

Length of metabolic normalization after rat islet cell transplantation depends on endocrine cell composition of graft and on donor age